Chapter 5 Long Bones
Alessandro Castriota-Scanderbeg, M.D.
Each limb consists of four segments, including a root
or zonoskeleton; a proximal segment or stylopodium, consisting of a single bone (humerus, femur); a
medial segment or zeugopodium, consisting of two
bones (radius and ulna; tibia and fibula); and a distal
part or autopodium, corresponding to hand and foot.
The complex processes involved in the formation of
these segments and pertinent genetic hints have been
reviewed in Chapter 6.
Development of the bones in the limbs takes place
for the most part by virtue of endochondral bone
formation, that is, transformation of the primitive
mesenchyma into an intermediate cartilage model,
which subsequently ossifies. First, a network of
immature, woven-fibered trabeculae (the primary
spongiosa) is produced. Later, the primary spongiosa
is replaced by secondary bone, which is either trabecular or cortical, depending on the location (Frost
1983). Ossification starts at approximately the midpoint of the cartilaginous model (primary ossification center) and proceeds toward both ends of the
bone until a plate of cellular activity is created at the
interface between the diaphysis and the epiphysis.
This growth plate, or physis, allows for longitudinal
growth of the bone until its final length is achieved.
The primary ossification centers for the femur make
their appearance around the 7th week of gestation,
while those for the humerus, radius, ulna, tibia, and
fibula appear around the 8th week of gestation. As
endochondral ossification proceeds, the mesenchymal cells surrounding the cartilaginous model undergo transformation into osteoblasts (intramembranous bone formation) and lay down bone in the
subperiosteal zone, which is destined to form the
cortex of the developing bone. By ossification of the
secondary centers within the epiphyses at the ends of
the bone, the epiphyseal cartilage is converted to
bone, except for a thin peripheral layer, which persists as articular cartilage of the intervening joint.
The tubular bones with secondary ossification centers at both ends are termed, by convention, ‘long’
bones, while those with a center at only one end are
termed ‘short’ bones. The secondary ossification cen-
ters for the head of the humerus, distal femur, and
proximal tibia make their appearance around the
36th week of gestation, while those for the femoral
head and capitulum of humerus do not appear until
the 2nd to the 6th month after birth. The distal epiphysis of radius usually appears around 12 months,
and the greater trochanter of femur and proximal
epiphysis of fibula at about 3 years of age. Ossification of the long bones extends a long way into childhood and early adolescence, with the patella developing at about 4 years, the capitulum of the radius at
5 years, the medial epicondyle of the humerus at
6 years, the distal epiphysis of the ulna at 7 years, the
olecranon of the ulna at 10 years, and the lateral epicondyle of the humerus and tubercle of the tibia at
11 years (Garn et al. 1967). With further growth, the
physeal plate becomes progressively narrowed and
finally disappears, allowing fusion between the epiphysis and the diaphysis.
At any stage of development, even when growth is
complete, the normal bone is an active, dynamic tissue in which the process of bone formation is balanced by that of bone resorption. This balance is accomplished by the integrated activity of specialized
bone cells, i.e., osteoblasts and osteoclasts, which are
enrolled into the process of growth, fracture healing,
modeling, and remodeling of the living human
skeleton (Resnick et al. 1995). Modeling is the dynamic process by which major adjustments in the
size and shape of the bones are produced. The
process of modeling, which depends heavily upon
the mechanical forces applied to the skeleton,
is most prominent in the immature skeleton until
adolescence, and results in a net increase in the
amount of bone tissue, especially in the subperiosteal location. Remarkable examples of bone
modeling in the tubular bones include: (a) drifting
of the midshaft, accomplished by endosteal bone
resorption and periosteal bone formation; and (b)
flaring of the metaphyses, accomplished by resorption along the periosteal surface and apposition in the endosteal surface. In this way the wide
metaphysis is substituted by a narrow diaphysis
274
Chapter 5 · Long Bones
as the bone grows in length. Remodeling is the dynamic process that modifies bone quality, causing
the structurally inferior woven-fibered bone of the
infant to give way to the more compact lamellar
bone of the adult (Resnick et al. 1995). In addition,
remodeling replaces aged or injured bone tissue
with new bone, a process requiring a tight balance
between resorption and formation of the cortical
and trabecular bone.
Some important alterations in the shape and contour of the tubular bones are emphasized in this
chapter, and the principal mechanisms of their development are discussed. The coexistence of different
‘shapes’ in a single bone (e.g., the long bones in osteopetrosis are bowed and widened, in addition to
being dense) precludes firm categorization of individual disorders in one section or another, a circumstance that is reflected in the large overlap within and
across sections in the chapter.
References
References
Frost HM. The skeletal intermediary organization. Metab Bone
Dis Relat Res 1983; 4: 281–90
Garn SM, Rohmann CG, Silverman FN. Radiographic standards for postnatal ossification and tooth calcification. Med
Radiogr Photogr 1967; 43: 45–66
Resnick D, Manolagas SC, Niwayama G, Fallon MD. Histogenesis, anatomy, and physiology of bone. In: Resnick D (ed.)
Diagnosis of bone and joint disorders.W. B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 609–51
Miller SC, Jee WS. The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat. Anat Rec 1979; 193: 439–62
Silverman FN. The bones: normal and variants. In: Silverman
FN, Kuhn JP (eds.) Caffey’s pediatric X-ray diagnosis. Year
Book Medical Publisher, Inc., Chicago, 1990, pp. 1465–527
Broad Tubular Bones
Abnormalities of the Shape
and Contour of the Long Bones
䉴 [Expanded tubular bones]
The delicate balance of bone resorption and bone
formation, as outlined above, can be altered by a
number of factors, including congenital and acquired
diseases and drugs, notably diphosphonates (Miller
and Jee 1979). As stated earlier, the modeling process
produces major changes in the shape and size of
the bones (Silverman 1990). Defective modeling of
the tubular bones can result in either increased or
reduced tubulation. Overtubulation, a condition of
diminished periosteal deposition, gives rise to long,
slim bones, whereas undertubulation is associated
with bone shortening and either diaphyseal or metaphyseal expansion. Pathologic conditions involving
undertubulation include most skeletal dysplasias
characterized by increased bone density, e.g., osteopetrosis and both craniometaphyseal and craniodiaphyseal dysplasias. In addition to modeling defects,
many other factors can lead to major changes in the
shape and contour of the long bones: defective endochondral bone formation within the physis (e.g.,
achondroplasia, especially the homozygous form),
bone marrow infiltration and expansion (e.g., anemias and storage diseases), muscle inactivity and disuse (e.g., neuromuscular disorders), inherent bone
weakening (e.g., osteomalacia), and several others. In
most cases, the final shape of the bone is the result of
a complex interaction between different and sometimes unrelated factors.
Several mechanisms can account for broadening of
the tubular bones, including defective modeling, cortical hyperostosis, bone marrow hyperplasia or infiltration, and new bone deposition in the periosteum
and adjacent soft tissues. As a consequence, broad
tubular bones are seen in a wide variety of disorders,
both congenital and acquired, including several
skeletal dysplasias, metabolic disorders, and hematological diseases. Depending on the underlying etiology, broadening of the long bones is focal or generalized, symmetrical or asymmetrical. This section offers an overview of the conditions characterized by
defective modeling and bone marrow infiltration/
hyperplasia. The subject of cortical hyperostosis is
addressed in the section of this chapter headed “Cortical Thickening.”
Failure of normal modeling of a tubular bone (undertubulation) can cause either diaphyseal or metaphyseal expansion, or both. Diaphyseal expansion is
typically seen in patients with diaphyseal dysplasia
(Camurati-Engelmann disease, OMIM 131300; Fig.
5.1), in which the tubular bones manifest enlarged
and sclerotic diaphyses, cortical thickening, and narrowing of the medullary cavity (Crisp and Brenton
1982; Neveh et al. 1984). Undermodeled tubular
bones with expanded diaphyses and thin cortices are
seen in craniodiaphyseal dysplasia (OMIM 122860,
218300), a disorder with severe sclerosis and hyper-
Abnormalities of the Shape and Contour of the Long Bones
Fig. 5.1. Diaphyseal dysplasia (Camurati-Engelmann disease)
in a 36-year-old woman. Note fusiform thickening of the cortex in the diaphyseal portion of the femur (site of intramembranous ossification). Cortical thickening is due to periosteal
and endosteal bone apposition. The external contour of the
bone is regular. The medullary cavity is narrowed. (From Vanhoenacker et al. 2000)
ostosis of the facial and skull bones (leontiasis
ossea). A severe modeling defect resulting in clubshaped metaphyseal expansion with cortical thinning, which is most prominent in the distal femurs, occurs in craniometaphyseal dysplasia (OMIM
123000, 218400). Metaphyseal widening does not become apparent until childhood, while in infancy the
disease manifests with diaphyseal sclerosis and normal metaphyses, thereby simulating diaphyseal dysplasia (McAlister and Herman 1995). Extensive sclerosis of the skull base and facial bones, with obliteration of the paranasal cavities, is characteristic of this
condition but is less prominent than in craniodiaphyseal dysplasia. In frontometaphyseal dysplasia
(OMIM 305620), changes in the long bones, including
metaphyseal widening and thin cortices, are similar
to, but milder than, those of craniometaphyseal dysplasia. The differential diagnosis is based on the
appearance of the facial bones (unaffected in frontometaphyseal dysplasia and diffusely sclerotic in
craniometaphyseal dysplasia) and pelvis (marked
flaring of iliac wings in frontometaphyseal dysplasia
and normal appearance in craniometaphyseal dysplasia). In metaphyseal dysplasia (Pyle disease,
275
OMIM 265900) the extreme expansion of the metaphysis, extending well into the diaphysis, leads to the
characteristic Erlenmeyer flask deformity in the
femur and tibia. Pyle disease resembles craniometaphyseal dysplasia in most respects. Distinctive features in Pyle disease include milder sclerosis of the
skull bones, with no symptoms of cranial nerve compression, and a more severe tubulation defect about
the metaphyses. Furthermore, the inheritance pattern is autosomal recessive in Pyle disease, and autosomal dominant in craniometaphyseal dysplasia. In
the autosomal recessive hereditary hyperphosphatasia (juvenile Paget disease, OMIM 239000) the tubular bones are markedly widened and bowed, with
thick or thin cortices and subsequent narrowing or
widening of the medullary cavity, which can hardly
ever be distinguished from the cortex. In oculo-dento-osseous dysplasia (OMIM 257850) failure of normal tubulation results in mild to moderate widening
of the tubular bones, involving either the metaphysis
or the entire shaft. In osteopetrosis, precocious type
(OMIM 259700) the homogeneously dense long
bones display undermodeled, club-shaped metaphyses. Osteopetrosis, delayed type (OMIM 166600) is
also characterized by varying degrees of impaired
bone modeling.
Enlargement of the tubular bones as a result of
bone marrow infiltration is usually associated with
cortical erosion and thinning. In lipid storage diseases, including Gaucher’s disease (OMIM 230800)
and Niemann-Pick disease (OMIM 257250), widening
of the medullary cavity with cortical diminution is
secondary to marrow infiltration by lipid-containing
cells (Matsubara et al. 1982). In both diseases modeling deformities also occur, especially at the distal
ends of the femoral shafts, resulting in the Erlenmeyer flask deformity (Resnick 1995; Lachman et al.
1973). In mucopolysaccharidosis I-H (Hurler disease,
OMIM 252800), the changes in the long tubular
bones, which are most prominent at the upper
extremities, include diaphyseal and metaphyseal expansion, cortical thinning, and delayed epiphyseal
ossification. In mucopolysaccharidosis VI (MaroteauxLamy syndrome, OMIM 253200) the tubular bones
are relatively short and show irregular diaphyseal
widening and submetaphyseal overconstriction. A
few patients with childhood lymphoproliferative disorders, including leukemia, lymphoma, and mastocytosis, manifest bony enlargement. More typical
manifestations in these disorders are bone destruction with periostitis and osteosclerosis, either focal
or diffuse. Conditions involving severe and longstanding anemia, such as thalassemia major, may
276
Chapter 5 · Long Bones
result in alteration of the long bone contour, with
metaphyseal and epiphyseal widening, cortical thinning, and a coarse, trabeculated appearance. These
alterations, which are due to reactive bone marrow
hyperplasia, are now prevented in developed countries by maintaining appropriate levels of serum
hemoglobin with transfusions.
Two major mechanisms are believed to cause
broadening of the long bones in neurofibromatosis
type 1 (OMIM 162220): (a) a modeling defect, resulting in metaphyseal expansion; and (b) periosteal
overgrowth secondary to subperiosteal hemorrhage
and/or soft tissue infiltration by neurofibromas,
which are subsequently incorporated into the cortex.
In hemophilia (OMIM 306700), extensive subperiosteal bleeding may eventually calcify over time
(Swischuk and John 1995, p. 198). New bone deposition at or around the periosteum can manifest as
overall ballooning of the parent bone. In Caffey
disease (OMIM 114000) bone deposition occurs
within the soft tissues surrounding the periosteum.
Subsequent fusion of the new bone tissue with the
cortex gives rise to broadening of the involved tubular bone.
Radiographic Synopsis
AP, lateral, and oblique projections. The corticodiaphyseal ratio, measured at the mid-shaft of the tibia
on AP projection, is increased in conditions with cortical thickening and decreased in conditions with
medullary expansion and cortical thinning. The ratio
is calculated by summing the widths of both cortices
and dividing the result by the entire width of the diaphysis. The normal corticodiaphyseal ratio in children over 18 months of age and adults is 0.48±0.09
(Bernard and Laval-Jeantet 1962).
1. Diaphyseal expansion; thick cortices; narrow
medullary cavity (diaphyseal dysplasia)
2. Diaphyseal expansion; thin cortices (craniodiaphyseal dysplasia)
3. Metaphyseal expansion; thin cortices; clubshaped distal femurs (Pyle disease; craniometaphyseal dysplasia; frontometaphyseal dysplasia)
4. Widening of the medullary cavity; cortical
diminution (storage diseases; lymphoproliferative
disorders; severe anemia)
5. Metaphyseal expansion; periosteal thickening
(neurofibromatosis type 1)
6. Periosteal thickening (hemophilia; Caffey disease)
Associations
• Achondrogenesis type 1
• Achondrogenesis type 2
• Anemia, severe
• Bleeding (hemophilia, trauma, battered child
syndrome, neurogenic fracture)
• Chromosome 8 trisomy syndrome
• Cleidocranial dysplasia
• Craniodiaphyseal dysplasia
• Craniometaphyseal dysplasia
• Craniometadiaphyseal dysplasia,
wormian bone type
• Diaphyseal dysplasia (Camurati-Engelmann)
• Diaphyseal dysplasia – anemia
• Diaphyseal dysplasia – proximal myopathy
• Dysosteosclerosis
• Dyssegmental dysplasia
• Endosteal hyperostosis (van Buchem, Worth)
• Exostoses, multiple heritable
• Fibrogenesis imperfecta ossium
• Fibrous dysplasia
• Gaucher disease
• GM1 gangliosidosis
• Hyperphosphatasia, hereditary
• Hypochondrogenesis
• Infantile multisystem inflammatory disease
• Kyphomelic dysplasia
• Mastocytosis
• McCune-Albright syndrome
• Mesomelic dysplasia (Langer)
• Metaphyseal dysplasia (Pyle disease)
• Mucolipidoses
• Mucopolysaccharidoses
• Neu-Laxova syndrome
• Neurofibromatosis
• Niemann-Pick disease
• Oculo-dento-osseous dysplasia
• Opsismodysplasia
• Osteogenesis imperfecta, type II
• Osteopetrosis
• Oto-palato-digital syndrome, type I
• Pachydermoperiostosis
• Pleonosteosis
• Schwarz-Lelek syndrome
• Scurvy
• Singleton-Merten syndrome
• Thanatophoric dysplasia
• Weissenbacher-Zweymuller syndrome
Abnormalities of the Shape and Contour of the Long Bones
References
Bernard J, Laval-Jeantet M. Le rapport cortico-diaphysaire tibial pendant la croissance. Arch Fr Pediatr 1962; 19: 805–17
Crisp AJ, Brenton DP. Engelmann’s disease of bone. A systemic
disorder? Ann Rheum Dis 1982; 41: 183–8
Lachman R, Crocker A, Schulman J, Strand R. Radiological
findings in Niemann-Pick disease. Radiology 1973; 108:
659–64
Matsubara T, Yoshiya S, Maeda M, Shiba R, Hirohata K. Histologic and histochemical investigation of Gaucher cells. Clin
Orthop 1982; 166: 233–42
McAlister WH, Herman TE. Osteochondrodysplasias, dysostoses, chromosomal aberrations, mucopolysaccharidoses,
and mucolipidoses. In: Resnick D (ed.) Diagnosis of bone
and joint disorders. W. B. Saunders Company, Philadelphia,
1995 (3rd ed.), pp. 4163–244
Naveh Y, Kaftori JK,Alon U, Ben-David J, Berant M. Progressive
diaphyseal dysplasia: genetics and clinical and radiologic
manifestations. Pediatrics 1984; 74: 399–405
Resnick D. Lipidoses, histiocytoses, and hyperlipoproteinemias. In: Resnick D (ed.) Diagnosis of bone and joint disorders. W. B. Saunders Company, Philadelphia, 1995 (3rd ed.),
pp. 2190–246
Swischuk LE, John SD. Differential diagnosis in pediatric radiology. Williams & Wilkins, Baltimore, 1995
Vanhoenacker FM, De Beuckeleer LH,Van Hul W, Balemans W,
Tan GJ, Hill SC, De Schepper AM. Sclerosing bone dysplasias: genetic and radioclinical features. Eur Radiol 2000;
10: 1423–33
Slender Tubular Bones
䉴 [Slim, elongated bones]
Activity is essential to the normal growth and development of bones. Inactivity from any cause, including neuromuscular disorders and prolonged immobilization or disuse, produces osseous, articular, and
soft tissue changes. Osteoporosis, growth disturbances and deformities, fractures, soft tissue atrophy
or – less frequently – hypertrophy, heterotopic ossification, cartilage atrophy, and synovitis are examples
of pathophysiologic responses to the altered equilibrium between muscle activity and normal growth
and integrity of the adjacent bones. The occurrence
of one or another of the changes mentioned is related to the nature of the underlying disorder and to the
patient’s age. Osteoporosis accompanying prolonged
immobilization, disuse, or paralysis can be focal or
generalized, depending on the causative factor. Although its pathogenesis is uncertain, a vascular
mechanism, with intraosseous venous stasis and
stimulation of osteoclastic activity, is likely (van
Ouwenaller et al. 1989). Changes in calcium homeostasis include hypercalcemia, hypercalciuria, hyper-
277
phosphoremia, and reduced levels of plasma 1,25-dihydroxyvitamin D, a pattern indicating suppression
of the parathyroid-1,25-dihydroxyvitamin D axis
(Stewart et al. 1982). Thinning of the long bones may
result from active bone resorption either at the level
of one of the three cortical envelopes (subperiosteal,
intracortical, and endosteal) or at the trabecular level. If the causative mechanism has been exerting its
effect since infancy, underdevelopment of the entire
affected skeletal area can occur. In these cases, the
long bones are gracile, with thin cortices and diaphyseal constriction. In addition to slender and hypoplastic long bones, patients with poliomyelitis
sometimes experience premature closure of the
growth plates and epiphyses about the ankle and
knee, with a ‘ball-in-socket’ epiphyseal appearance
and pes cavus deformity (Richardson et al. 1984).
Long-standing muscle hypotonia and flaccidity give
rise in the immature skeleton to slim bones, coxa valga deformity, increased height of the vertebral bodies, and narrowing of the intervertebral disks (Hsu
1982). Children with cerebral palsy and muscle
spasticity can manifest flexion contracture of the
hips, hip dislocation, equinus deformity of the ankle,
scoliosis, lordosis, and pelvic obliquity (Mayfield
et al. 1981). Children with Erb-Duchenne paralysis (damage to the 5th and 6th cervical roots) or
Klumpke’s paralysis (damage to the 7th and 8th cervical roots) who do not recover over time may display hypoplasia of the involved arm, slender bones,
and a variety of shoulder deformities, including hypoplasia and elevation of the scapula, shallow glenoid fossa, and tilted coracoid process (Pollock and
Reed 1989).
Thin, gracile bones occur in osteogenesis imperfecta type I (OMIM 166200) and type IV (OMIM 166220)
and in the rare lethal skeletal dysplasia with gracile
bones (OMIM 602361), a short-limbed dwarfing condition with markedly thin diaphyses, diaphyseal fractures, thin ribs and clavicles, facial anomalies, and
positional abnormalities of hands and feet (Maroteaux et al. 1988).
Several connective tissue disorders feature slender
limbs. In these cases, muscular atrophy and weakness
act in concert with the inherent bone defect in determining bone gracility and slenderness. Marfan syndrome (OMIM 154700) is an autosomal dominant
disorder of the connective tissue primarily involving
the eyes, the skeleton, and the cardiovascular system.
Affected patients are typically tall, with long slim
limbs, thin subcutaneous fat, and muscle hypotonia.
Arachnodactyly with hyperextensibility is typical
(Magid et al. 1990). Radiographic changes of Marfan
278
Chapter 5 · Long Bones
Fig. 5.2. Congenital contractural arachnodactyly in a 13-yearold girl. Note slim, elongated long bones in the shank
syndrome are similar to those occurring in other conditions with ‘marfanoid’ skeletal abnormalities. For
example, homocystinuria (OMIM 236200), an autosomal recessive disorder with an inborn defect of methionine metabolism and excessive plasma levels of
homocysteine, shows long slim limbs (dolichostenomelia), arachnodactyly, and a constellation of vascular, brain, ocular and skeletal derangements, including vascular narrowing or dilatation, atheromatous lesions, ocular lens subluxation, cutaneous malar
flush, microcephaly, dural calcifications, enlarged
paranasal sinuses, widening of the diploic space of
the skull, prognathism, scoliosis, compression fractures of the spine with ‘codfish’ vertebrae, sternal deformities, large metaphyses and epiphyses, and ligamentous laxity (Brenton 1977). The presence of osteoporosis, mental retardation, and vascular complications allows differential diagnosis from Marfan syndrome (Smith 1967). Slender tubular bones are also
seen in congenital contractural arachnodactyly (Beals
syndrome, OMIM 121050), another inherited disorder of the connective tissue manifesting with joint
contractures (knees, elbows, hips), arachnodactyly,
progressive kyphoscoliosis, and abnormally shaped,
‘crumpled’ ears (Beals and Hecht 1971; Hecht and
Beals 1972; Epstein et al. 1968; McKusick 1975)
(Fig. 5.2). Beals syndrome differs from Marfan syndrome in the absence of ocular abnormalities, while
cardiovascular abnormalities such as mitral valve
prolapse are occasionally found. Patients with Stickler
syndrome (arthro-ophthalmopathy, OMIM 108300), a
connective tissue disorder with an autosomal dominant mode of inheritance, also have a marfanoid
habitus, with distinct orofacial changes, including
cleft palate and micrognathia (Opitz et al. 1972).
Other disorders with slim long bones are those
involving an appearance suggestive of advanced
age, including Cockayne syndrome, progeria, and
Werner syndrome. Patients with Cockayne syndrome
(OMIM 216400) show profound postnatal growth
deficiency, early-onset (1st year of life) senile-type
changes, mental retardation, central and peripheral
nervous system abnormalities, ocular abnormalities,
photosensitive skin, a characteristic facies, and slim
long limbs (Riggs and Seiberg 1972). Cockayne syndrome is similar in various features to progeria
(OMIM 176670), a probably autosomal dominant
disorder with a precocious senile appearance that
is striking in degree, thin calvarium with open
fontanels, alopecia, thin skin, atrophy of subcutaneous fat, deficient growth beginning during the first
months of life, early-onset atherosclerosis, osteoporosis, facial hypoplasia, receding chin, beaked
nose, and slender tubular bones and ribs (DeBusk
1972; Gillar et al. 1991). Mental development is normal, and acro-osteolysis of distal phalanges and clavicles are features peculiar to progeria (Reichel et al.
1971). In Werner syndrome (OMIM 277700), an autosomal recessive disorder (gene WNR mapped to 8p12
is similar to DNA helices), senile-type changes are
usually not apparent until early adult life. This syndrome features absence of the pubertal growth spurt,
short stature, skin atrophy with thick fibrous subcutaneous tissue, gray sparse hair, premature loss of
teeth, cataract, slim extremities, small hands and feet,
narrow face with beaked nose, atherosclerosis, heterotopic calcifications, osteoporosis, and an elevated
risk of malignancy (Fleischmajer and Nedwich 1973;
Adoue 1997). Thin, gracile tubular bones and ribs are
characteristic radiographic manifestations of Hallermann-Streiff syndrome (OMIM 234100), a sporadic
disorder with proportionately small stature, craniofacial abnormalities (brachycephaly with frontal
bossing, malar and mandibular hypoplasia, small
pointed nose, narrow palate, dental defects, skin atrophy, thin sparse hair), ocular abnormalities (mi-
Abnormalities of the Shape and Contour of the Long Bones
279
the foot, ulnar deviation of the hand, coalition in the
carpus and tarsus, dislocation of hip and patella,
fibular hypoplasia, and scoliosis are common features (Poznanski and La Rowe 1970). In the rare autosomal recessive Marinesco-Sjögren syndrome (OMIM
248800) the principal features include cerebellar ataxia, congenital cataracts, mental and physical retardation, myopathy and skeletal anomalies, including
kyphoscoliosis, clubfoot, gracile bones, cubitus valgus, short metatarsals and metacarpals, coxa valga,
and microcephaly (Brogdon et al. 1996) (Fig. 5.3a,b).
a
b
Fig. 5.3 a, b. Marinesco-Sjögren syndrome. Note slenderness
of the long bones in the a lower and b upper extremities. Cubitus valgus, and short metacarpals are also apparent in b. (From
Brogdon et al. 1996)
crophthalmia, cataract, strabismus), and skeletal abnormalities (slender bones, wormian bones, decreased number of sternal ossification centers)
(Stone 1975; Cohen 1991; Scheuerle 1999). The autosomal recessive 3 M syndrome (OMIM 273750) is
characterized by proportionate dwarfism, face with
frontal bossing, flattened malar region, short nose
with upturned nares, long philtrum, prominent
mouth with thick lips, and slender tubular bones and
ribs (Feldmann et al. 1989). Slim, stick-like tubular
bones are also found in the Pena-Shokeir phenotype
(fetal akinesia/hypokinesia sequence, OMIM 208150),
a lethal disorder characterized by multiple joint
ankylosis, facial anomalies, and pulmonary hypoplasia (Hall 1986). The designation arthrogryposis is
currently applied to the clinical picture of multiple,
nonprogressive joint contractures of prenatal onset.
A number of underlying disorders manifest with
multiple congenital contractures. Both active and
passive motion are limited, the bones are gracile, and
the soft tissues are hypotrophic. Equinovarus of
Radiographic Synopsis
1. Thin, vertically oriented femoral neck (coxa valga); underdeveloped, slender tubular bones; osteoporosis; fractures; soft tissue atrophy; soft tissue and bone infections; heterotopic ossification;
cartilage atrophy (neuromuscular disorders, immobilization)
2. Thin, gracile bones; multiple fractures (osteogenesis imperfecta, ‘lethal skeletal dysplasia with
gracile bones’)
3. Dolichostenomelia; arachnodactyly (Marfan syndrome, homocystinuria, congenital contractural
arachnodactyly)
4. Slender tubular bones; bulky metaphyses and epiphyses; curved fibulas (Cockayne syndrome)
5. Slim tubular bones (progeria, Werner syndrome,
Hallermann-Streiff syndrome, 3M syndrome, Marinesco-Sjögren syndrome)
6. Gracile bones with slim tubular bones; multiple
joint contractures (Pena-Shokeir phenotype, arthrogryposis)
Associations
• Arthrogryposis
• Caudal dysplasia sequence
• Cockayne syndrome
• Congenital contractural arachnodactyly (Beals
syndrome)
• Hallermann-Streiff syndrome
• Homocystinuria
• Hypopituitarism
• Intrauterine dwarfism, peculiar facies and thin
bones with multiple fractures
• Lethal skeletal dysplasia with gracile bones
• 3M syndrome
• Marfan syndrome
• Marinesco-Sjögren syndrome
• Marshall-Smith syndrome
• Muscular dystrophies
• Neurofibromatosis
• Neuromuscular disorders
280
•
•
•
•
•
Chapter 5 · Long Bones
Osteogenesis imperfecta types I, IV
Pena-Shokeir phenotype
Progeria
Pterygium syndrome (lethal multiple pterygium)
Winchester syndrome
References
Adoue DP. Images in clinical medicine. Werner’s syndrome.
N Engl J Med 1997; 337: 977
Beals RK, Hecht F. Congenital contractural arachnodactyly: a
heritable disorder of connective tissue. J Bone Joint Surg
Am 1971; 53: 987–93
Brenton DP. Skeletal abnormalities in homocystinuria. Postgrad Med J 1977; 53: 488–96
Brogdon BG, Snow RD, Williams JP. Skeletal findings in Marinesco-Sjogren syndrome. Skeletal Radiol 1996; 25: 461–5
Cohen MM Jr. Hallermann-Streiff syndrome: a review. Am J
Med Genet 1991; 41: 488–99
DeBusk FL. The Hutchinson-Gilford progeria syndrome.
J Pediatr 1972; 80: 697–724
Epstein CJ, Graham CB, Hodgkin WE, Hecht F, Motulsky AG.
Hereditary dysplasia of bone with kyphoscoliosis, contractures, and abnormally shaped ears. J Pediatr 1968; 73:
379–86
Feldmann M, Gilgenkrantz S, Parisot S, Zarini G, Marchal C.
3 M dwarfism: a study of two further sibs. J Med Genet
1989; 26: 583–5
Fleischmajer R, Nedwich A. Werner’s syndrome. Am J Med
1973; 54: 111–8
Gillar PJ, Kaye CI, McCourt JW. Progressive early dermatologic changes in Hutchinson-Gilford progeria syndrome.
Pediatr Dermatol 1991; 8: 199–206
Hall JG. Analysis of Pena Shokeir phenotype. Am J Med Genet
1986; 25: 99–117
Hecht F, Beals RK. ‘New’ syndrome of congenital contractural
arachnodactyly originally described by Marfan in 1896.
Pediatrics 1972; 49: 574–9
Hsu JD. Skeletal changes in children with neuromuscular disorders. Prog Clin Biol Res 1982; 101: 553–7
Magid D, Pyeritz RE, Fishman EK. Musculoskeletal manifestations of the Marfan syndrome: radiologic features. AJR Am
J Roentgenol 1990; 155: 99–104
Maroteaux P, Cohen-Solal L, Bonaventure J, Peter MO, Francannet C, Guibaud P, Moraine C. Syndromes letaux avec
gracilité du squelette. Arch Franc Pediatr 1988; 45: 477–81
Mayfield JK, Erkkila JC, Winter RB. Spine deformity subsequent to acquired childhood spinal cord injury. J Bone Joint
Surg Am 1981; 63: 1401–11
McKusick VA. The classification of heritable disorders of connective tissue. Birth Defects Orig Art Ser 1975; 11: 1–9
Opitz JM, Franc T, Herrmann J. The Stickler syndrome. N Engl
J Med 1972; 286: 546–7
Pollock AN, Reed MH. Shoulder deformities from obstetrical
brachial plexus paralysis. Skeletal Radiol 1989; 18: 295–7
Poznanski AK, La Rowe PC. Radiographic manifestations of
the arthrogryposis syndrome. Radiology 1970; 95: 353–8
Reichel W, Bailey JA, Zigel S, Garcia-Brunel R, Knox G. Radiological findings in progeria. J Am Geriatr Soc 1971; 19:
657–74
Richardson ML, Helms CA, Vogler JB 3rd, Genant HK. Skeletal
changes in neuromuscular disorders mimicking juvenile
rheumatoid arthritis and hemophilia.AJR Am J Roentgenol
1984; 143: 893–7
Riggs W Jr, Seiberg J. Cockayne’s syndrome: roentgen findings.
Am J Roentgenol 1972; 116: 623–33
Scheuerle A. Commentary on Hallermann-Streiff Syndrome:
experience with 15 patients and review of the literature.
J Craniofac Surg 1999; 10: 225
Smith SW. Roentgen findings in homocystinuria. Am J
Roentgenol Radium Ther Nucl Med 1967; 100: 147–54
Stewart AF, Adler M, Byers CM, Segre GV, Broadus AE. Calcium
homeostasis in immobilization: an example of resorptive
hypercalciuria. N Engl J Med 1982; 306: 1136–40
Stone WC. Hallermann-Streiff syndrome and progeria. South
Med J 1975; 68: 1139–41
Van Ouwenaller C, Uebelhart D, Chantraine A. Bone metabolism in hemiplegic patients. Scand J Rehabil Med 1989; 21:
165–70
Bowed Tubular Bones
䉴 [Curved bones]
Bowing of the long bones can be focal or generalized,
depending on whether the causative mechanism
acts locally (trauma, infection) or diffusely (skeletal
dysplasias, metabolic disorders, malformation syndromes). Although traumas in children mostly cause
plastic bending fractures, injuries to the epiphysis
occasionally lead to more permanent focal bowing by
interfering with the normal bone growth.
Long bones whose structure is inherently weak for
any reason are prone to bending changes, especially
when exposed to the effects of postural influences
and weight-bearing. One typical such situation is
offered by rickets and osteomalacia, two terms describing gross histopathologic and radiologic abnormalities that are common to more than 50 diseases
varying in cause and clinical presentation (Pitt 1981).
The term ‘rickets’ means a breakdown in the orderly
development and mineralization of the growth plate,
with deficient mineralization of the zone of provisional calcification.‘Osteomalacia’ means inadequate
or delayed calcium hydroxyapatite deposition on
bone matrix, with a relative excess of osteoid accumulation in mature cortical and spongy bone
(Mankin 1974). Therefore, before fusion of the
growth plates rickets and osteomalacia can coexist.
Their coexistence facilitates the radiographic diagnosis, which is difficult in the presence of osteomalacia alone. Children with rickets show characteristic
changes at the growth plates, notably at the costochondral junctions of the middle ribs, the distal ends
of the femur, radius, and ulna, the proximal end of
Abnormalities of the Shape and Contour of the Long Bones
a
b
Fig. 5.4 a–c. Rickets. a In a 2-month-old boy during the early phase of treatment the distal ends of
the radius and ulna are irregularly mineralized,
frayed, and cupped. Both bones are undermineralized, with a coarse trabecular pattern. The provisional zones of calcification are partially recalcified and appear as a transverse line of increased
density located well beyond the ends of the shafts.
b, c. In a 13-month- old girl 1 month after the beginning of treatment the metaphyses are cupped,
with a marginal band of increased density due
to recalcification of the provisional zone. Note
bowing deformity of the ulna (arrows), tibias and
fibulas
the humerus, and both ends of the tibia. Features include growth plate widening, decreased density, and
irregularities in the zone of provisional calcification,
metaphyseal cupping and fraying, increased epimetaphyseal distance, and bone rarefaction, which is
most prominent in the metaphyses (Fig. 5.4a–c).Various bone deformities can develop, depending on the
child’s age at disease onset and the duration of disease. In early infancy, changes in the skull are striking, with occipital flattening (caused by supine postural influences) and prominent frontal and parietal
bones (caused by accumulation of osteoid). During
infancy and early childhood, characteristic bowing
deformities of the long bones in the arms and legs
become apparent, which are secondary to abnormal
postures assumed by the child and/or to displacement of the growth centers by unequal musculotendinous pulls. With the effects of weight-bearing,
bowing deformities in the lower legs tend to worsen,
and progressive scoliosis may develop. As mentioned
above, when rachitic changes are lacking the radiographic recognition of osteomalacia can be ex-
281
c
tremely difficult. In fact, osteopenia, a cardinal feature of osteomalacia, is not specific. Cortical hyperostosis resulting from (partial) mineralization of excessive subperiosteal osteoid deposition can be
diagnostically misleading. Difficulties in diagnosis
can also arise from the superimposition of hyperparathyroidism and osteitis fibrosa cystica, a complication of long-standing low serum calcium levels
(Renton 1998). More specific signs of osteomalacia
are so-called Looser’s zones, or milkman’s pseudofractures. They are seen as focal areas of radiolucency reflecting unmineralized osteoid, which are oriented at right angles to the cortex and incompletely
span the diameter of the bone (Sabean 1966; Meema
and Meema 1975). Their bilateral and symmetrical
distribution, and their occurrence at specific sites
(ribs, pubis, inner borders of scapula and femur, posterior margin of ulna) are characteristic, and allow
radiographic differentiation from other disorders
with similar findings, such as Paget disease and fibrous dysplasia. Many rachitic and osteomalacic syndromes are caused by vitamin D deficiency (dietary
282
Chapter 5 · Long Bones
䊴
Fig. 5.5. X-linked hypophosphatemia in a 77-year-old woman.
Pronounced femoral bowing is associated with an active middiaphyseal lateral Looser zone (arrow) and proliferative
changes along the linea aspera (arrowheads). (Reprinted, with
permission, from Hardy et al. 1989)
deficiency, gastrointestinal malabsorption, prematurity, liver disease, anticonvulsive therapy, renal osteodystrophy, parathyroid disorders) or by primary
renal tubular loss of phosphate (X-linked hypophosphatemia, disorders of renal tubular dysfunction
subsumed under ‘Fanconi syndromes,’ neoplasms,
ingestion of such drugs as ipofosfamide) (Pitt 1991).
However, other rachitic and osteomalacic syndromes,
such as axial osteomalacia, hypophosphatasia, and
metaphyseal chondrodysplasia, are known, in which
no detectable vitamin D, calcium and phosphorus
metabolism abnormality can be found (Pitt 1995).
X-Linked hypophosphatemia (OMIM 307800), the
most common form of renal tubular rickets and
osteomalacia, is inherited as an X-linked dominant
trait commonly resulting from a de novo mutation
a
b
Fig. 5.6 a–c. Hypophosphatasia, congenital lethal form. a Female fetus of unspecified gestational age. Extensive ossification defects involving both ends of the femur associated with
marked bowing give a ‘chromosome-like’ appearance. b Male
fetus at 39 weeks of gestational age. The femur is short, with
c
splayed metaphyses and central lucent ossification defects extending only slightly into the diaphyses. c Male fetus of unspecified gestational age. Almost normally modeled femoral
diaphysis with marked metaphyseal flaring and irregularities.
(From Shohat et al. 1991)
Abnormalities of the Shape and Contour of the Long Bones
283
Fig. 5.7. Metaphyseal chondrodysplasia, Schmid type in a 3year-old boy. Note bowed femurs, widened and irregular metaphyses, coxa vara, and relatively large capital femoral epiphyses. The pelvis is normal
Fig. 5.8. Campomelic dysplasia in a newborn who died shortly after birth. Note thin and bowed femora with anterolateral
angulation, short and anteriorly curved tibias, and hypoplastic
fibulas. The tibial cortical profile is thickened on the medial
side (concavity of the curve) and thinned on the lateral side.
The pelvis is hypoplastic, with unossified pubic bones.
(Reprinted, with permission, from Mastroiacovo et al 1990)
(Filisetti et al. 1999). The basic metabolic defect is
hypophosphatemia secondary to phosphate loss at
the renal tubuli, with normal serum calcium levels.
The clinical and radiographic features vary with patient age. In children, rickets-like changes at the
growth plates are typical. Affected individuals are
short, short-limbed and bowlegged. In adults, bone
reinforcement lines, Looser zones, endosteal hyperostosis, osteoarthritis, multiple ossifications around
ligament attachments (enthesopathy) and joints, and
bowing deformity of the long bones in the lower extremities are common (Hardy et al. 1989) (Fig. 5.5).
Hypophosphatasia is a rare disorder of defective
skeletal mineralization characterized by deficiency of
tissue and serum alkaline phosphatase and by excessive blood levels and urinary excretion of phosphoethanolamine, inorganic pyrophosphate, and pyridoxal-5-phosphate. Based on the age of the patient at
manifestation and the predominant clinical findings,
the disorder is best classified into four forms: perinatal, infantile, childhood, and adult. The congenital
lethal form (OMIM 241500) of hypophosphatasia, a
perinatally lethal condition with autosomal recessive
inheritance, displays severely impaired or absent
bone ossification, which is most prominent in the
skull and at the ends of the long bones. The radiographic spectrum of abnormalities is not uniform
in all patients. The appearance of the femurs, for instance, may be dominated by bowing deformities
reminiscent of campomelic dysplasia or by metaphyseal ossification defects (Shohat et al. 1991) (Fig.
5.6a–c). Hypophosphatasia tarda can begin within
the first 6 months of life (infantile form, OMIM
241500), in early childhood (childhood form, OMIM
241510), or in adulthood (adult form, OMIM 146300).
Radiologic manifestations of the infantile and child-
284
Chapter 5 · Long Bones
a
Fig. 5.9. Antley-Bixler syndrome. Postmortem radiograph of a
male neonate. Note marked bowing of both femurs, bilateral
humeroradial synostosis, and inverse U shape of the distal
scapula. (From Mortier et al. 1997)
hood forms include rachitic changes, delayed ossification of the calvarium and skull base, large metaphyseal ossification defects in the long bones and
ribs and, frequently, angulation of the long bones.
The association of bowing deformities and ricketslike changes in the limbs in hypophosphatasia permits its differentiation from osteogenesis imperfecta,
with which it can sometimes be confused. The infantile form is lethal in about 50% of cases. Both infantile and childhood forms have an autosomal recessive mode of inheritance. The adult form, which has
autosomal dominant inheritance, features varying
degrees of long bone bowing, pseudofractures, osteoporosis, craniostenosis (nonuniform, as in childhood), premature loss of teeth, ectopic calcifications
of the vertebral ligaments and disks, articular chondrocalcinosis, and nephrocalcinosis (Fallon et al.
1984). Instances of prenatal hypophosphatasia, with
severe manifestations in utero followed by a benign
b
Fig. 5.10 a, b. Kyphomelic dysplasia in a female infant a at
birth and b at 1 year of age. Note short, laterally bowed long
bones, notably the femurs. The metaphyses are wide and irregular. Note significant attenuation of the bowing deformities at
1 year. (From Cisarik et al. 1999)
postnatal course and spontaneous improvement of
long bone angulation, have been reported (Pauli et al.
1999). Metaphyseal chondrodysplasia, Schmid type
(OMIM 156500), a condition with autosomal dominant inheritance, is the most common form of metaphyseal dysplasia, presenting in the second year of
Abnormalities of the Shape and Contour of the Long Bones
285
a
Fig. 5.12. Dyssegmental dysplasia, Rolland-Desbuquois type.
Newborn male. Note short tubular bones with metaphyseal
widening, and lateral bowing of tibias and fibulas. (From
Langer et al. 1976)
b
Fig. 5.11 a, b. Dyssegmental dysplasia, Silverman-Handmaker
type in a stillborn infant (same case as in Fig. 3.27 a, b). a Note
extremely short and broad long tubular bones, with marked
metaphyseal expansion. The femurs are bowed posteriorly,
whereas tibias and fibulas are bowed laterally.Also note the extensive segmentation defects of lumbar and sacral vertebrae;
short, round and densely calcified iliac bones; broad pubis and
ischia; and clubfeet. b Similar changes are visible in the long
bones of the upper extremities. Note acute angulation of the
radius. (From Fasanelli et al. 1985)
life with short stature, bowed legs, and waddling gait
(Lachman et al. 1988). Radiologic features are similar
to those seen in X-linked hypophosphatemic rickets,
but calcium, phosphorus, and alkaline phosphatase
levels are in the normal ranges. As in rickets, the
growth plates, especially those in the more rapidly
growing areas, are widened, with fine projections extending from the metaphyses. Cupping, fraying, and
splaying of the metaphyses, most prominent in the
lower extremities and in the lower femurs, are common features. Oversized proximal femoral epiphyses
(before the age of 10 years), short femoral neck, coxa
vara, and genu varum are also characteristic findings
in this condition (Fig. 5.7). It differs from rickets in
that the metaphyses are well mineralized and both
radiolucent areas within the cortex (Looser’s zones)
and signs of osteitis fibrosa cystica are lacking. The
disease has a benign course, and even though bowing
deformities persist into adulthood, they do not cause
joint derangements or osteoarthritis. Radiologic differentiation from metaphyseal dysplasia, McKusick
type (OMIM 250250) is based on the greater involvement of the metaphyses at the knees and less prominent coxa vara and bowed legs in the latter condition.
Limb bowing, most pronounced in the lower extremities, typically occurs in campomelic dysplasia
(OMIM 114290), an autosomal dominant disorder
due to mutation of the SHOX9 gene on chromosome
17q24.3-q25.1. Distinct features include thin and
curved femurs with anterolateral angulation, short
and anteriorly angulated tibias, and hypoplastic fibulas (Fig. 5.8). Bowing also affects the upper extremities, albeit to a lesser extent. Other findings that help
differentiate campomelic dysplasia from other disorders associated with curved limbs include small
scapulas (not seen, for instance, in kyphomelic dys-
286
a
c
Chapter 5 · Long Bones
b
Fig. 5.13 a–c. Weismann-Netter-Stuhl syndrome
in a 5-year-old girl. a Bilateral medial bowing of
the tibias and fibulas. Note cortical thickening in
the mid-shaft of both bones, and irregular bone
trabeculation. b Bilateral diaphyseal bowing of
the femurs with external convexity and thickening of the medial cortex. c Marked anterior bowing of the femur, with striking thickening of its
posterior cortex and irregular bony trabeculae
in the mid-shaft. (From Tieder et al. 1995)
plasia), hypoplasia of cervical vertebrae and vertebral pedicles in the thoracic spine, large head, small
facies, small hands, and slender clavicles and ribs
(Hall and Spranger 1980). Although the mechanism
responsible for bowing of long bones in campomelic
dysplasia remains unknown, defects in the composition of glycosaminoglycans at the stage of the cartilaginous model, which are sometimes followed by
fracture of the bone collar in the earlier stage of ossification, have been suggested (Nogami et al. 1986;
Pazzaglia and Beluffi 1987). Antley-Bixler syndrome
(OMIM 207410) is similar to classic campomelic dysplasia in several clinical and radiologic points, including campomelia of the femurs, scapular hypoplasia, joint contractures, urogenital abnormalities, car-
diac and central nervous system abnormalities, and
sex reversal (Mortier et al. 1997). However, distinct
features in Antley-Bixler syndrome include radiohumeral synostosis (100%), arachnodactyly (70%),
brachycephaly with frontal bossing (100%), craniosynostosis (70%), depressed nasal bridge (100%),
choanal stenosis/atresia (80%), and dysplastic ears
(100%) (Rumball et al. 1999; Lee et al. 2001) (Fig. 5.9).
Another classic condition with bent bones is kyphomelic dysplasia (OMIM 211350), which has an autosomal recessive inheritance. Major clinical and radiologic manifestations include disproportionately
short stature apparent at birth, rhizomesomelic limb
shortening, lateral bowing of the long bones, especially the femurs, sometimes with dimples over the
Abnormalities of the Shape and Contour of the Long Bones
a
287
b
Fig. 5.14 a, b. Pachydysostosis in a boy. a At 1 month old the
boy has bowing of the fibula with dorsal convexity and enlargement. b When the same boy is 9 years of age significant
remodeling has occurred. Persistence of bowing is minimal,
and there is mild enlargement in the distal portion of the fibula. (Reprinted, with permission, from Maroteaux et al. 1991)
Fig. 5.15 a, b. Melnick-Needles syndrome in a 4-year-old
girl. a Note the highly characteristic angulation of the
proximal portion of the radial
shaft. The cortical contour
of the humerus is irregular.
b Note the characteristic
S-shaped bowing deformity of
both tibias and fibulas. (From
Eggli et al. 1992)
a
b
288
Chapter 5 · Long Bones
Fig. 5.16 a, b. Mandibuloacral dysplasia in a 7-year-old
girl. The bilateral notch of the
humeral shaft resulting in a
bowing deformity of both
humeri is very peculiar. The
long bones are slender. (From
Hoeffel et al. 2000)
a
b
apex of the angulation, flared irregular metaphyses, a
short narrow chest, mildly dysmorphic facial features, improvement of bone changes with advancing
age, and normal psychomotor development (Pallotta
et al. 1999). Bowing of the long bones differs from
campomelic dysplasia in that the curved bones in
kyphomelic dysplasia are short and broad, with
flared irregular metaphyses (Hall and Spranger 1979)
(Fig. 5.10a,b). Bowing of the long tubular bones is also
a manifestation of dyssegmental dysplasia, SilvermanHandmaker (OMIM 224410) and Rolland-Desbuquois (OMIM 224400) types. In addition to being
bowed, the long tubular bones are short and broad,
with marked metaphyseal flaring. The clinical and
radiographic picture is more severe in the early lethal
Silverman-Handmaker type (Fig. 5.11a,b) than in the
Rolland-Desbuquois type (Fig. 5.12), a condition that
resembles Kniest dysplasia and allows survival beyond the newborn period (Langer et al. 1976). The
autosomal dominant Weismann-Netter-Stuhl sy
drome (OMIM 112350) is characterized by bilateral
bowing of the tibias and fibulas, and possibly of
other tubular bones (Francis et al. 1991). Tibial curvature is typically anterior and medial, and is associ-
ated with thickening of the posterior tibial cortex.
Similar findings are also frequent in the femurs
(Fig. 5.13a–c). The fibula is curved and may be, enlarged, and thickened in a way that causes it to resemble the corresponding tibia (‘tibialization’ of the fibula). Additional features include short stature, delayed
ambulation, mild mental retardation, horizontalization of the sacrum, brachydactyly, and coxa vara. Similar manifestations, but confined to the fibula, occur in
pachydysostosis (Maroteaux et al. 1991) (Fig. 5.14a,b).
Spontaneous regression of the defect over a period of
years is the rule. Anterolateral bending deformity of
the tibias, often associated with marked cortical
thickening, is characteristic of neurofibromatosis type
1 (OMIM 162220). The radiographic aspects may not
be discernible from those of the Weismann-NetterStuhl syndrome, but usually the fibulas are gracile
and hypoplastic in neurofibromatosis, and wide and
thick in Weismann-Netter-Stuhl syndrome. Bowlegs
in patients with osteogenesis imperfecta (OMIM
166200, 166210, 166220, 259420) may be related to osteomalacia or represent a sequel to multiple telescopic fractures that have developed pre- or postnatally.
Limb bowing is most striking in type IIB/III osteo-
Abnormalities of the Shape and Contour of the Long Bones
genesis imperfecta (OMIM 259420) (Beighton et al.
1983). Bowing of long bones also occurs in parastremmatic dwarfism (OMIM 168400), a very rare,
probably autosomal dominant disorder, with severe
dwarfism, short neck, kyphoscoliosis, contractures of
major joints, and progressive skeletal deformities
(twisted dwarfism). Characteristic features in this
disorder include the ‘lacy’ appearance of the iliac
crests, the ‘flocky’ or ‘woolly’ appearance of the metaphyses, and a coarse trabeculated pattern with areas
of dense stippling of metaphyses, epiphyses, and
apophyses (Langer et al. 1970). The early lethal condition termed boomerang dysplasia (OMIM 112310)
features short, bowed, boomerang-shaped long bones
in the legs, a characteristic facies, bilateral radial and
fibular aplasia, iliac hypoplasia, generalized ossification delay, and absent pubic bones (Kozlowski et al.
1985; Winship et al. 1990). In Melnick-Needles syndrome (OMIM 309350), the tibias show a characteristic S-shaped bowing deformity. Bowing of other long
bones, notably the radius and ulna, is common. In
particular, an acute curve of the proximal end of the
radius is typical (Eggli et al. 1992; Memis et al. 1992)
(Fig. 5.15a,b). Diaphyseal overconstriction with bending of the bone at the site and reminiscent of the
changes in Melnick-Needles syndrome has been described in patients with mandibuloacral dysplasia
(Fig. 5.16a,b). A wide overlap of phenotypic manifestations, including bowing of the femurs, among
oto-palato-digital syndrome type II (OMIM 304120),
boomerang dysplasia, atelosteogenesis type I (OMIM
108720) and type III (OMIM 108721), and the lethal
male phenotype of Melnick-Needles syndrome
(OMIM 309350) has been reported in sibs (Nishimura et al. 1997). Madelung deformity (OMIM 304990),
a defect consisting primarily in dorsolateral bowing
of the radius, is discussed in a separate section.
Radiographic Synopsis
1. Osteoporosis, decreased number of trabeculae,
‘coarse’ trabecular pattern; radiolucent areas in
the cortex; widened metaphyses; deossification
and unsharpness of epiphyseal centers; bowing of
long bones (osteomalacia, rickets)
2. Areas of increased bone density; osteosclerotic
foci around the cartilaginous end-plates in the
spine; periarticular and vascular calcification
(osteomalacia, especially accompanying renal
osteodystrophy)
3. Growth plate changes (often mild); bowing of long
bones, especially in the extremities; mild osteopenia (X-linked hypophosphatemia, children). Coarsened trabecular pattern; Looser’s zones; pseudo-
4.
5.
6.
7.
289
fractures; elevated bone density; ‘paradoxical’ calcification and ossification of ligaments, tendons at
their osseous insertion, annulus fibrosus, joint
capsules, and ligamentum flavum, with narrowing
of the spinal canal; osteoarthritis (X-linked hypophosphatemia, adults)
Femoral bowing; diffuse metaphyseal flaring; irregularity and widening of the growth plate, most
pronounced at knees; enlarged capital femoral
epiphyses; severe coxa vara; anterior cupping,
splaying and sclerosis of the ribs; marked lumbar
lordosis (metaphyseal dysplasia, Schmid type)
Anterolateral angulation of femurs; anterior angulation and shortening of tibias; hypoplastic fibulas; mild shortening and bowing of forearms
(campomelic dysplasia)
Short, broad, and bowed femurs with irregular,
flared metaphyses; shortening and bowing of
other tubular bones, especially the humeri (kyphomelic dysplasia)
Lacy appearance of the iliac crests; ‘flocky’ or
‘woolly’ metaphyseal appearance; severe epiphyseal deformation (parastremmatic dwarfism)
Associations
• Achondroplasia
• Antley-Bixler syndrome
• Blount disease
• Boomerang dysplasia
• Campomelic dysplasia
• Diastrophic dysplasia
• Dyssegmental dysplasia
• Ellis-van Creveld syndrome
• Faulty intrauterine fetal positioning
• Fuhrmann syndrome
• Hyperparathyroidism
• Hyperphosphatasia
• Hypochondroplasia
• Hypophosphatasia
• Infection
• Kyphomelic dysplasia
• Larsen syndrome
• Madelung deformity
• Metaphyseal chondrodysplasia (Schmid type)
• Metaphyseal dysplasia (Pyle disease)
• Mucolipidoses
• Mucopolysaccharidoses
• Neurofibromatosis
• Osteodysplasty (Melnick-Needles syndrome)
• Osteogenesis imperfecta
• Osteomalacia
• Oto-palato-digital syndrome, type II
• Parastremmatic dwarfism
290
•
•
•
•
•
•
•
•
Chapter 5 · Long Bones
Pseudoachondroplasia
Rickets
Rothmund-Thomson syndrome
Spondyloepimetaphyseal dysplasia
Spondylometaphyseal dysplasia
Trauma
Weissmann-Netter-Stuhl syndrome
X-Linked hypophosphatemia
References
Beighton P, Spranger J, Versveld G. Skeletal complications
in osteogenesis imperfecta. A review of 153 South African
patients. S Afr Med J 1983; 64: 565–8
Cisarik F, Kozlowski K, Masel J, Sillence D. Variability in
kyphomelic dysplasia. Pediatr Radiol 1999; 29: 551–7
Eggli K, Giudici M, Ramer J, Easterbrook J, Madewell J. Melnick-Needles syndrome. Four new cases. Pediatr Radiol
1992; 22: 257–61
Fallon MD, Teitelbaum SL, Weinstein RS, Goldfischer S, Brown
DM, Whyte MP. Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. Medicine 1984; 63: 12–24
Fasanelli S, Kozlowski K, Reiter S, Sillence D. Dyssegmental
dysplasia: report of two cases and review of the literature.
Skeletal Radiol 1985; 14: 173–7
Filisetti D, Ostermann G, von Bredow M, Strom T, Filler G,
Ehrich J, Pannetier S, Garnier JM, Rowe P, Francis F, Julienne A, Hanauer A, Econs MJ, Oudet C. Non-random distribution of mutations in the PHEX gene, and under-detected
missense mutations at non-conserved residues. Eur J Hum
Genet 1999; 7: 615–9
Francis GL, Jelinek JJ, McHale K, Adamson M, Levin SW. The
Weismann-Netter syndrome: a cause of bowed legs in
childhood. Pediatrics 1991; 88: 334–7
Hall BD, Spranger J. Familial congenital bowing with short
bones. Radiology 1979; 132: 611–4
Hall BD, Spranger JW. Campomelic dysplasia. Further elucidation of a distinct entity. Am J Dis Child 1980; 134: 285–9
Hardy DC, Murphy WA, Siegel BA, Reid IR,Whyte MP. X-linked
hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features. Radiology 1989; 171:
403–14
Hoeffel JC, Mainard L, Chastagner P, Hoeffel CC. Mandibuloacral dysplasia. Skeletal Radiol 2000; 29: 668–71
Kozlowski K, Sillence D, Cortis-Jones R, Osborn R. Boomerang
dysplasia. Br J Radiol 1985; 58: 369–71
Lachman RS, Rimoin DL, Spranger J. Metaphyseal chondrodysplasia, Schmid type: clinical and radiographic delineation with a review of the literature. Pediatr Radiol 1988;
18: 93–102
Langer LO Jr, Petersen D, Spranger JW. An unusual bone dysplasia: parastremmatic dwarfism. AJR Am J Roentgenol
1970; 110: 550–60
Langer LO Jr, Gonzalez-Ramos M, Chen H, Espiritu CE, Courtney NW, Opitz JM. A severe infantile micromelic chondrodysplasia which resembles Kniest disease. Eur J Pediatr
1976; 123: 29–38
Lee HJ, Cho DY, Tsai FJ, Shen WC. Antley-Bixler syndrome,
description of two new cases and review of the literature.
Pediatr Neurosurg 2001; 34: 33–9
Mankin HJ. Rickets, osteomalacia, and renal osteodystrophy.
Part II. J Bone Joint Surg Am 1974; 56: 352–86
Maroteaux P, Freisinger P, Le Merrer M. Pachydysostosis of the
fibula. J Bone Joint Surg Br 1991; 73: 842–5
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarotti MS. Difetti congeniti e sindromi malformative. McGrawHill, Milan, 1990
Meema HE, Meema S. Improved roentgenologic diagnosis of
osteomalacia by microradioscopy of hand bones. Am J
Roentgenol Radium Ther Nucl Med 1975; 125: 925–35
Memis A, Ustun EE, Sener RN. Case report 717. Osteodysplasty (Melnick-Needles syndrome). Skeletal Radiol 1992; 21:
132–4
Mortier GR, Rimoin DL, Lachman RS. The scapula as a window to the diagnosis of skeletal dysplasias. Pediatr Radiol
1997; 27: 447–51
Nishimura G, Horiuchi T, Kim OH, Sasamoto Y. Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II,
boomerang dysplasia, atelosteogenesis type I and type III,
and lethal male phenotype of Melnick-Needles syndrome.
Am J Med Genet 1997; 73: 132–8
Nogami H, Oohira A, Kuroyanagi M, Mizutani A. Congenital
bowing of long bones: clinical and experimental study.
Teratology 1986; 33: 1–7
Pallotta R, Ehresmann T, Roggini M, Fusilli P. Kyphomelic dysplasia: clinical and radiologic long-term follow-up of one
case and review of the literature. Radiology 1999; 212:
847–52
Pauli RM, Modaff P, Sipes SL, Whyte MP. Mild hypophosphatasia mimicking severe osteogenesis imperfecta in utero:
bent but not broken. Am J Med Genet 1999; 86: 434–8
Pazzaglia UE, Beluffi G. Radiology and histopathology of the
bent limbs in campomelic dysplasia: implications in the aetiology of the disease and review of theories. Pediatr Radiol 1987; 17: 50–5
Pitt MJ. Rachitic and osteomalacic syndromes. Radiol Clin
North Am 1981; 19: 581–99
Pitt MJ. Rickets and osteomalacia are still around. Radiol Clin
North Am 1991; 29: 97–118
Pitt MJ. Rickets and osteomalacia. In: Resnick D (ed.) Diagnosis of joint and bone disorders. W.B. Saunders Company,
Philadelphia, 1995 (3rd ed.), pp. 1885–922
Renton P. Radiology of rickets, osteomalacia and hyperparathyroidism. Hosp Med 1998; 59: 399–403
Rumball KM, Pang E, Letts RM. Musculoskeletal manifestations of the Antley-Bixler syndrome. J Pediatr Orthop B
1999; 8: 139–43
Sabean HB. The role of radiology in the investigation of skeletal “demineralization”. N S Med Bull 1966; 45: 307–9
Shohat M, Rimoin DL, Gruber HE, Lachman RS. Perinatal
lethal hypophosphatasia; clinical, radiologic and morphologic findings. Pediatr Radiol 1991; 21: 421–7
Tieder M, Manor H, Peshin J, Alon US. The Weismann-NetterStuhl syndrome: a rare pediatric skeletal dysplasia. Pediatr
Radiol 1995; 25: 37–40
Winship I, Cremin B, Beighton P. Boomerang dysplasia. Am J
Med Genet 1990; 36: 440–3
Abnormalities of the Shape and Contour of the Long Bones
291
Cortical Thickening
䉴 [Increase in thickness and density
of the cortex, hyperostosis]
This section deals with a heterogeneous group of unrelated disorders, either congenital or acquired, focal
or widespread, whose pathological and radiographic
stigmata are those of cortical hyperostosis. Conditions involving generalized bone sclerosis, such as
osteopetrosis, dysosteosclerosis, pyknodysostosis
and osteosclerosis, are addressed in Chapter 9.
Thickening of bone cortex may be secondary to overproduction or diminished resorption of cortical
bone. Overproduction may be related to periosteal
bone formation, endosteal bone formation, or both.
The term periostitis defines the pathologic situation
characterized by infiltration of the periosteum by
inflammatory cells, elevation and/or violation of the
periosteal membrane, and new bone deposition in
the periosteum or the soft tissues adjacent to it (Spjut
and Dorfman 1981). Subsequent merging of the newly formed periosteal bone with the cortex leads to
cortical hyperostosis. Compared with that in adults,
the periosteal membrane in infants and children is
thicker, more highly vascularized, metabolically
more active, and more loosely attached to the underlying cortex. This may well explain two characteristics of the periosteal membrane of the immature
skeleton: the increased susceptibility (a) to being lifted from the parent bone and (b) to being stimulated
to form osseous tissue. The following discussion will
focus first on situations of cortical hyperostosis associated with periostitis and next on situations of ‘primary’ cortical hyperostosis without periostitis.
The list of diseases associated with periostitis is
very long indeed and includes infections (osteomyelitis, syphilis, tuberculosis), tumors (leukemia,
lymphoma, metastases, primary bone tumors,
eosinophilic granuloma), metabolic disorders (copper deficiency, hyperphosphatasia, hyperparathyroidism, hyperthyroidism, rickets, scurvy, hypervitaminosis A), skin disorders (ichthyosis congenita, urticaria pigmentosa, pyoderma, burns, frostbite,
chronic cellulitis), trauma, juvenile rheumatoid
arthritis, sickle cell anemia, prostaglandin-induced
periostitis (Fig. 5.17), dactylitis, venous insufficiency,
and several bone disorders (pachydermoperiostosis,
secondary hypertrophic osteoarthropathy, idiopathic
cortical hyperostosis, fibrous dysplasia, Paget disease, recurrent symmetrical periostitis) (Reeder and
Felson 1993; Kozlowski and Beighton 1995). However, diffuse periosteal new bone deposition can be
Fig. 5.17. Prostaglandin-induced periostitis in a 45-day-old
child. This baby with severe tetralogy of Fallot was given
prostaglandin E1, a specific relaxant of ductal smooth muscle,
intravenously to maintain the patency of the ductus arteriosus
and allow adequate pulmonary blood flow before the necessary surgical intervention. Periostitis developed in the first few
days after treatment. Note periosteal thickening along the external diaphyseal surface of both femurs
seen in normal infants, especially prematures, perhaps in response to exuberant bone growth. The
periosteal reaction accompanying osteomyelitis is
often multi-layered like ‘onion peeling,’ a pattern
similar to that encountered in certain malignant neoplasms (Fig. 5.18a,b), including Ewing’s sarcoma
(OMIM 133450). When the periosteal reaction associated with osteomyelitis involves only a single layer
of thick bone, the changes are reminiscent of eosinophilic granuloma or traumatic periostitis (Resnick
and Niwayama 1995b). A thick periosteal reaction is
seen in the presence of eosinophilic granuloma once
the lesion originally located within the medullary
cavity encroaches on the cortex and erodes its endosteal surface. In childhood leukemia and lymphoma, periosteal bone formation is secondary to invasion of the cortex via the haversian canals by the
proliferating marrow cells. These cells then reach a
subperiosteal location, causing elevation of the periosteal membrane and bone formation. The periosteal new bone deposition of the healing phase of
a fracture results in single or multiple bony shells,
which subsequently merge with the parent bone. In
the battered child syndrome, multiple fractures with
periosteal reactions at different stages of evolution
are a clue to the diagnosis.A special case of periosteal
new bone deposition is that occurring in the lower
extremities in patients with chronic venous insufficiency, possibly as a response to local hypoxia
(Dannels and Nashel 1983). The term dactylitis refers
to a pathologic process of varying etiology (sickle
292
Chapter 5 · Long Bones
Fig. 5.18 a, b. Primitive neuroectodermal tumor (PNET)
in a 13-year-old boy. a Anteroposterior and b lateral radiograph of the shank shows
cortical thickening and periosteal irregularities and
spiculation along the lateral
and posterior aspects of the
tibia. The epiphysis is not involved. The boy had tuberous
sclerosis. (From Hindman et
al. 1997)
a
b
cell anemia, tuberculosis, syphilis, leprosy, fungal and
pyogenic disorders, leukemia, scurvy, hypervitaminosis A, trauma, infantile cortical hyperostosis)
involving a periostitic reaction of the short tubular
bones in the hands and feet, with or without bone
destruction. Soft tissue swelling is uniformly present
(Worrall and Butera 1976; Andronikou and Smith
2002). In primary hypertrophic osteoarthropathy
(pachydermoperiostosis, OMIM 167100), an autosomal dominant condition with enlargement of the
hands and feet, digital clubbing, coarsening of the
skin of the face and scalp, and swollen joints, a cardinal feature is widespread and symmetrical cortical
thickening, which is most prominent in the tubular
bones of the extremities (Vogl and Goldfischer 1962).
Periostitis extends across the epiphyses and produces a shaggy appearance of the bony contour, resulting in expansion of the diaphyses and narrowing
of the medullary cavity. The familial incidence of the
disease has long been recognized (Rimoin 1965). Recessive inheritance is suggested by the several examples of consanguineous parents (Matucci-Cerinic et
al. 1989). Changes in the peripheral blood supply,
resulting in local hypoxia, have been suggested as the
initiating event of periosteal new bone formation
(Fam et al. 1983). Additional findings include ligamentous ossification, bony bridges across joints
causing joint ankylosis, soft tissue swelling of the distal digits, and tuftal osteolysis (Joseph and Chacko
1985). The findings in pachydermoperiostosis resemble those of secondary hypertrophic osteoarthropathy, an association of digital clubbing, arthritis, and
periostitis that can arise as a complication of various
diseases, including bronchogenic carcinoma, pleural
mesothelioma, pulmonary abscess, bronchiectases,
Hodgkin lymphoma, cyanotic congenital heart diseases, biliary cirrhosis, ulcerative colitis, Crohn disease, and others (Sillero Garcia et al. 1978). Lack of
family history, late onset, significant pain and tenderness about the joints, and linear periosteal bone formation not usually extending into the epiphysis are
distinctive features of the condition (Fig. 5.19a–c).
Of the several theories proposed to explain the
pathogenesis of the condition, none of which is entirely adequate (Resnick and Niwayama 1995a), those
that have gained the most support include increased
vascular flow carrying poorly oxygenated blood to
the periosteum (Racoceanu et al. 1971), presence of
humoral substances toxic to the periosteum (Jao et
al. 1969), and a neurogenic mechanism mediated by
the vagus nerve (Rutherford et al. 1969). In thyroid
acropachy, an uncommon complication of thyrotoxicosis usually arising several years after the onset of
treated hyperthyroidism, clinical and radiographic
Abnormalities of the Shape and Contour of the Long Bones
Fig. 5.19 a–c. Hypertrophic
osteoarthropathy, secondary,
in a 13-year-old boy with nasopharyngeal
carcinoma.
Note linear periosteal new
bone formation (arrows) involving the diaphyses of the
long bones in the upper (a)
and lower (b, c) extremities.
(From Varan A et al. 2000)
a
b
c
Fig. 5.20 a, b. Infantile cortical hyperostosis (Caffey disease) in a 2-month-old male
baby (same case as in
Fig. 2.23). a Note marginal hyperostosis on the lateral edge
of the left ilium, extending
from the iliac crest to the midportion of the acetabular cavity. b Observe massive cortical
new bone formation encasing
the shaft of the tibia and fibula. The femur and epiphyses
are not involved
a
b
293
294
Chapter 5 · Long Bones
manifestations include exophthalmos, soft tissue
swelling of the fingers and toes, pretibial myxedema,
clubbing of the fingers, and periostitis (Resnick
1995). Periosteal proliferation, primarily involving
the diaphyses of the metacarpals, metatarsals, and
proximal and middle phalanges, especially at their
radial ends, is characteristic (Vanhoenacker et al.
2001). Extension to other bones, including the long
bones, is uncommon. Periosteal new bone formation
follows soft tissue infiltration with myxedematous
tissue, but the ultimate cause of this process remains
unknown. Pretibial myxedema and a clinical history
of thyroid dysfunction are distinguishing features.
Infantile cortical hyperostosis (Caffey disease, OMIM
114000) is a rare disorder with onset before the 5th
month of life, presenting as fever of abrupt onset and
soft tissue swelling. The radiographic stigmata of the
disease are those of a periosteal bone reaction (Jackson and Lyne 1979). The mandible, clavicles, and ribs
are the bones most frequently involved, but changes
at other sites, notably the tubular bones, are also
common (Finsterbush and Rang 1975) (Fig. 5.20a,b).
Cortical hyperostosis, the hallmark of the disease,
results from blending of the newly formed bone in
the soft tissues adjacent to the periosteum with the
cortex of the parent bone. In the long bones, the
lesions of Caffey disease are confined to the shafts,
whereas the epiphyses are often spared. Distribution
of the lesions is asymmetrical. In many instances,
clinical and radiographic manifestations improve
and subside over a period of 6 months to 1 year. In a
few cases, the disease course is less favorable, with
recurrences well into adult life (Pajewski and Vure
1967; Taj-Eldin and Al-Jawad 1971). The pathogenesis is unknown. The inflammatory nature of the acute
disease manifestations has led to the hypothesis of an
immune reaction triggered by a viral infection (Silverman 1976) or an allergic response to altered collagen tissue (McEnery and Nash 1973). A vascular occlusion secondary to thrombocytosis has also been
suggested (Pickering and Cuddigan 1969). Although
the disease has somewhat unusual features for a
hereditary disorder (it rarely appears after 5 months
of age; it is characterized by fever and swelling of
involved bones; skeletal abnormalities disappear
over time), its occurrence in many members of the
same family over one or more generations has underscored the importance of genetic factors, autosomal
dominant inheritance being the most likely (Gerrard
et al. 1961; van Buskirk et al. 1961).
A number of metabolic disorders and intoxications are characterized by cortical hyperostosis in
the tubular bones. In rickets and scurvy in children
the radiographic pattern is sometimes similar to that
of Caffey disease, although absence of epiphyseal
involvement and spontaneous resolution are distinctive features of the latter. Cortical hyperostosis accompanying hypervitaminosis A is obvious at around
1 year of life, affecting the metatarsals and sparing
the mandible and facial bones (Frame et al. 1974;
Lian and Wu 1986). It can be impossible to differentiate prostaglandin-induced periostitis from Caffey disease. Fluorosis is characterized by osteoporosis in the
early stages, and by a later appearance of exuberant
and irregular periosteal bone deposition, osteophytosis, and ligamentous ossification (Lian and Wu
1986). GM1 gangliosidosis type I (OMIM 230500), a
storage disease with accumulation of ganglioside in
neurons, in histiocytes of the liver and spleen, and in
renal glomerular epithelium, involves severe cerebral
degeneration leading to death within the first 2 years
of life and skeletal deformities resembling those seen
in Hurler disease. Radiographically the condition is
also undistinguishable from mucolipidosis II (I-cell
disease, OMIM 252500), and it is characterized in
early infancy by abundant periosteal bone formation
of the long tubular bones, uniformly wide tubular
bones in the hands and feet, rib widening, coarse trabecular pattern, and mild vertebral abnormalities. In
later infancy and early childhood, dysplasia of the
pelvis, overconstriction and irregular contour of the
shafts of the long tubular bones, and osteoporosis
become apparent (Spranger et al. 1974).
Distinct skeletal dysplasias feature variable degrees of cortical thickening. A combination of exuberant periosteal and endosteal bone formation in
the diaphyses of the long bones, symmetrical in distribution and with a fusiform appearance of the cortex and smooth outer contour, is typical for diaphyseal dysplasia (Camurati-Engelmann disease, OMIM
131300) (Kaftori et al. 1987; Kumar et al. 1981). The
process of bone resorption and formation is intensely active in this disorder. A similar but much milder
and more localized radiographic pattern occurs in
hereditary multiple diaphyseal sclerosis (Ribbing’s
disease, OMIM 601477) (Seeger et al. 1996). Cortical
thickening can also result from new bone apposition
at the endosteal side of a tubular bone. The van
Buchem type (OMIM 239100) and the Worth type
(OMIM 144750) of endosteal hyperostosis are characterized by widespread osteosclerosis, with predominant involvement of the skull and mandible. Symptoms are more severe in van Buchem disease than in
Worth disease. The autosomal recessive van Buchem
disease occurs early in life and takes the form of severe mandibular enlargement, compromise of cra-
Abnormalities of the Shape and Contour of the Long Bones
Fig. 5.21. Melorheostosis
in a 20-year-old woman.
Irregular, thickened bars
of tibial sclerosis extend
longitudinally from the
cortical profile deep into
the medullary cavity.
(From Brown et al. 2000)
nial nerves, widened nasal bridge, prominent forehead, and cortical thickening of the tubular bones
with periosteal excrescences (Eastman and Bixler
1977). The autosomal dominant Worth disease is
clinically benign, manifesting in late childhood with
asymmetrical enlargement of the facial bones, especially the jaw, and palatal thickening (torus palatinus). The cranial nerves are not usually involved. The
tubular bones show endosteal hyperostosis, with
encroachment of variable extent on the medullary
cavity, in the absence of any obvious evidence of severe modeling defects (Greenspan 1991). Sclerosteosis (OMIM 269500) is clinically and radiographically
similar, and probably related, to endosteal hyperosto-
295
sis. This recessive sclerosing disorder is characterized by gigantism, a characteristic facies with prominent asymmetrical mandible, a broad and flat nasal
bridge, hypertelorism, cranial nerve palsies, deafness, variable syndactyly of the 2nd and 3rd fingers
with radial deviation, nail dysplasia, and possibly
increased intracranial pressure in adulthood. The
tubular bones show cortical sclerosis and thickening,
and lack of diaphyseal constriction. The process of
osteosclerosis is widespread, with predominant involvement of the skull and mandible, and significant
involvement of the spine and pelvis (Beighton 1988).
The main radiographic feature in melorheostosis
(OMIM 155950) is the presence of dense osseous
excrescences abutting on the cortical profile of one
bone, or of different bones within the same limb, and
extending along the longitudinal bone axis in the
shape of flowing candle wax (Freyschmidt 2001)
(Fig. 5.21). Hyperostosis is mainly cortical, but endosteal hyperostosis with secondary medullary
stenosis also occurs. The pathogenesis is obscure.
Based on the specific pattern of lesion distribution,
the role of sclerotomes, corresponding to areas of the
embryonic skeleton supplied by individual spinal
sensory nerves, has been emphasized by Murray and
McCredie (1979), who speculate that the sclerosing
lesions represent the late result of a segmental sensory nerve lesion. Melorheostosis has been reported
in association with other sclerosing dystrophies,
including osteopoikilosis and osteopathia striata
(Abrahamson 1968). Other possible associations include neurofibromatosis type 1, tuberous sclerosis,
infantile cortical hyperostosis, Gardner syndrome,
and fibrous dysplasia. In hereditary hyperphosphatasia (juvenile Paget disease, OMIM 239000) there is
generalized demineralization, calvarial thickening,
expansion and bowing of the long tubular bones, and
widening of the short tubular bones. Alkaline phosphatase is elevated. Thickening of the cortices on the
inner side of the bowed long bones and loss of the
discrete cortical shadow in other sites are features specific to this condition (Fig. 5.22a,b). The bone manifestations are bilateral and symmetrical, and there is
an increased tendency to fractures (Guibaud 1970).
Neurofibromatosis type 1 (OMIM 162220) can show
massive and bizarre periosteal bone overgrowth.
Moreover, bending deformities of the tibias, with anterolateral angulation, and gracile, malformed fibulas, are characteristic. The pathogenesis of periosteal
thickening is not known. Subperiosteal hemorrhages
and/or soft tissue infiltration by neurofibromas that
are subsequently incorporated into the cortex are
probably primary events, but an intrinsic abnormali-
296
Chapter 5 · Long Bones
a
b
Fig. 5.22 a, b. Hereditary hyperphosphatasia in a 15-month-old
girl. The long bones in the upper (a) and lower (b) extremities
are markedly widened, and are undermineralized, with coarse
trabeculation and loss of corticomedullary differentiation. The
femora are bowed, and there is prominent cortical thickening
on the inner side of the bowing. (From Tüysüz et al. 1999)
ty of the periosteum cannot be ruled out (Steenbrugge et al. 2001; Pitt et al. 1972).
Osteomas are single lesions arising from the periosteum and each consisting of a protruding mass of
abnormally dense but otherwise normal bone. They
occur most commonly in the skull and facial bones,
but can also be found in the tubular bones (Stern et
al. 1985; Broderick et al. 1980). The pathogenesis is
uncertain, one theory suggesting that osteomas are
the sclerotized end-stage of fibrous dysplasia (Jaffe
1958) while another disputes that they represent
hamartoma-like processes (Aegerter and Kirkpatrick
1975). Osteomas are easily distinguished from osteochondromas on the basis of the absence of spongy
bone and cartilaginous cap. Multiple osteomas can
be the first manifestation of Gardner syndrome
(OMIM 175100), an autosomal dominant disease
characterized by colonic polyposis, osteomatosis,
and soft tissue tumors (Chang et al. 1968). In the tubular bones, including those of the hands and feet,
the osseous lesions do not have the usual appearance,
but rather manifest as localized cortical thickening
that simulates the nodular osseous excrescences of
tuberous sclerosis.
Radiographic Synopsis
1. Single (or multiple) focus protruding from the
surface of a bone, homogeneously dense, with
smooth or lobulated margins (osteoma)
2. Dense, often bizarre osseous excrescences involving one or several bones of a single limb,
with undulating, irregular bony contour (melorheostosis)
3. Cortical thickening in the diaphyses of tubular
bones, especially the long bones, involving the
internal and external surfaces, with narrowing
of the medullary cavity, sparing of epiphyses,
smooth external contour (diaphyseal dysplasia)
4. Shaggy periosteal bone formation with cortical
thickening, diaphyseal expansion and medullary
narrowing; epiphyseal involvement; ligamentous
ossification; bony bridges across the joints; tuftal
osteolysis (pachydermoperiostosis)
5. Elevation of the periosteum; multiple bony layers around the periosteum, cortical thickening
(secondary hypertrophic osteoarthropathy)
6. Profound cortical hyperostosis, mostly involving
the mandible, the clavicles, and the ribs (Caffey
disease)
7. Enlargement of the mandible; sclerosis of the
skull base and calvarium; cortical thickening in
the tubular bones; sclerotic ribs and clavicles;
Abnormalities of the Shape and Contour of the Long Bones
8.
9.
10.
11.
osteosclerosis of the neural arches and spinous
processes in the spine (endosteal hyperostosis,
van Buchem and Worth types)
Generalized osteosclerosis with predominant involvement of the skull; endosteal cortical hyperostosis of the tubular bones with undertubulation (sclerosteosis)
Progressive generalized osteosclerosis; lack of differentiation between cortex and medullary cavity;
metaphyseal expansion; transverse radiolucent
metaphyseal lines; multiple fractures; ‘bone within bone’ appearance (osteopetrosis, precocious
type and, to a lesser extent, delayed type)
Diffuse osteosclerosis; lack of differentiation
between the cortex and the medullary cavity;
modeling defect with marked metaphyseal expansion compared with the diaphysis; pathologic fractures; dental anomalies; platyspondyly
with irregular vertebral end-plates (dysosteosclerosis)
Irregular thickening of the cortices of the tubular bones, with loss of definition between the cortex and the medullary bone (hyperphosphatasia)
Associations
• Acromegaly
• Anderson syndrome
• Battered child syndrome
• Craniodiaphyseal dysplasia
• Dactylitis
• Dentino-osseous dysplasia
• Desmoid syndrome
• Diaphyseal dysplasia (Camurati-Engelmann)
• Diaphyseal dysplasia – proximal myopathy
• Diaphyseal medullary stenosis – bone malignancy
– Hardcastle
• Distal osteosclerosis
• Dubowiz syndrome
• Endosteal hyperostosis (van Buchem)
• Endosteal hyperostosis (Worth)
• Erdheim-Chester disease
• Fibrous dysplasia
• Fluorosis
• Frontometaphyseal dysplasia
• Gardner syndrome
• Gaucher disease
• Gigantism
• GM1 gangliosidosis
• Hereditary multiple diaphyseal sclerosis
(Ribbing disease)
• Histiocytosis
• Hyperostosis generalisata with striation of the
bones
297
• Hyperostosis with dysproteinemia or hyperphosphatemia
• Hyperparathyroidism
• Hyperphosphatasia, hereditary
• Hypertrophic osteoarthropathy, secondary
• Hypothyroidism
• Infantile cortical hyperostosis (Caffey disease)
• Klippel-Trenaunay-Weber syndrome
• Koller syndrome
• Lenz-Majewski syndrome
• Mannosidosis
• McCune-Albright syndrome
• Melorheostosis
• Mucolipidosis II (I-cell disease)
• Neurofibromatosis type I
• Osteoma
• Osteomyelitis
• Osteopetrosis
• Osteosclerosis, dominant type (Stanescu)
• Pachydermoperiostosis
• Paget disease
• Pancreatitis
• Prostaglandin-induced periostitis
• Pyknodysostosis
• Rickets
• Sclerosteosis
• Scurvy
• Sickle cell anemia
• Thickened cortical bone/congenital neutropenia
• Thyroid acropachy
• Trauma
• Tricho-dento-osseous syndrome
• Tuberous sclerosis
• Tubular stenosis syndrome (Kenny-Caffey)
• Tumoral calcinosis
• Tumors
• Ulnar-metaphyseal dysplasia syndrome
• Venous insufficiency, chronic
• Vitamin A intoxication
• Vitamin D intoxication
• Weissmann-Netter-Stuhl syndrome
References
Abrahamson MN. Disseminated asymptomatic osteosclerosis
with features resembling melorheostosis, osteopoikilosis,
and osteopathia striata. Case report. J Bone Joint Surg Am
1968; 50: 991–6
Aegerter EE, Kirkpatrick JA Jr. Orthopedic diseases: physiology, pathology, radiology. W.B. Saunders Company, Philadelphia 1975 (4th ed.), p. 496
Andronikou S, Smith B.“Spina ventosa” – tuberculous dactylitis. Arch Dis Child 2002; 86: 206
298
Chapter 5 · Long Bones
Beighton P. Sclerosteosis. J Med Genet 1988; 25: 200–3
Broderick T, Resnick D, Usselman J. Case report 123: osteoid
osteoma of the tibia with removal confirmed on specimen
tomography. Skeletal Radiol 1980; 5: 193–5
Brown RR, Steiner GC, Lehman WB. Melorheostosis: case report with radiologic-pathologic correlation. Skeletal Radiol
2000; 29: 548–52
Chang CH, Piatt ED, Thomas KE, Watne AL. Bone abnormalities in Gardner’s syndrome. Am J Roentgenol Radium Ther
Nucl Med 1968; 103: 645–52
Dannels EG, Nashel DJ. Periostitis. A manifestation of venous
disease and skeletal hyperostosis. J Am Podiatry Assoc
1983; 73: 461–4
Eastman JR, Bixler D. Generalized cortical hyperostosis (van
Buchem’s disease): nosological considerations. Radiology
1977; 125: 297–303
Fam AG, Chin-Sang H, Ramsay CA. Pachydermoperiostosis:
scintigraphic, thermographic, plethysmographic, and capillaroscopic observations. Ann Rheum Dis 1983; 42: 98–102
Finsterbush A, Rang M. Infantile cortical hyperostosis. Followup of 29 cases. Acta Orthop Scand 1975; 46: 727–36
Frame B, Jackson CE, Reynolds WA, Umphrey JE. Hypercalcemia and skeletal effects in chronic hypervitaminosis A.
Ann Intern Med 1974; 80: 44–8
Freyschmidt J. Melorheostosis: a review of 23 cases. Eur Radiol
2001; 11: 474–9
Gerrard JW, Holman GH, Gorman AA, Morrow IH. Familial
infantile cortical hyperostosis. J Pediatr 1961; 59: 543–8
Greenspan A. Sclerosing bone dysplasias – a target-site approach. Skeletal Radiol 1991; 20: 561–83
Guibaud P. Hereditary hyperphosphatasia. Pediatrie 1970; 25:
235–8
Hindman BW, Gill HK, Zuppan CW. Primitive neuroectodermal tumor in a child with tuberous sclerosis. Skeletal Radiol 1997; 26: 184–7
Jackson DR, Lyne ED. Infantile cortical hyperostosis. Case report. J Bone Joint Surg Am 1979; 61: 770–2
Jaffe HL. Tumors and tumorous conditions of the bones and
joints. Lea & Febiger, Philadelphia, 1958, p. 138
Jao JY, Barlow JJ, Krant MJ. Pulmonary hypertrophic osteoarthropathy, spider angiomata, and estrogen hyperexcretion in neoplasia. Ann Intern Med 1969; 70: 581–4
Joseph B, Chacko V. Acro-osteolysis associated with hypertrophic pulmonary osteoarthropathy and pachydermoperiostosis. Radiology 1985; 154: 343–4
Kaftori JK, Kleinhaus U, Naveh Y. Progressive diaphyseal dysplasia (Camurati-Engelmann): radiographic follow-up and
CT findings. Radiology 1987; 164: 777–82
Kozlowski K, Beighton P. Gamut index of skeletal dysplasias:
an aid to radiodiagnosis. Springer, London, 1995 (2nd ed.),
pp. 10–1
Kumar B, Murphy WA, Whyte MP. Progressive diaphyseal dysplasia (Engelmann disease): scintigraphic-radiographicclinical correlations. Radiology 1981; 140: 87–92
Lian ZC, Wu EH. Osteoporosis – an early radiographic sign of
endemic fluorosis. Skeletal Radiol 1986; 15: 350–3
Matucci-Cerinic M, Cinti S, Morroni M, Lotti T, Nuzzaci G,
Lucente E, di Lollo S, Ceruso M, Cagnoni M. Pachydermoperiostosis (primary hypertrophic osteoarthropathy):
report of a case with evidence of endothelial and connective tissue involvement. Ann Rheum Dis 1989; 48: 240–6
McEnery G, Nash FW. Wiskott-Aldrich syndrome associated
with idiopathic infantile cortical hyperostosis (Caffey’s disease). Arch Dis Child 1973; 48: 818–21
Murray RO, McCredie J. Melorheostosis and the sclerotomes: a
radiological correlation. Skeletal Radiol 1979; 4: 57–71
Pajewski M, Vure E. Late manifestations of infantile cortical
hyperostosis (Caffey’s disease). Br J Radiol 1967; 40: 90–5
Pickering D, Cuddigan B. Infantile cortical hyperostosis associated with thrombocythaemia. Lancet 1969; II: 464–5
Pitt MJ, Mosher JF, Edeiken J. Abnormal periosteum and bone
in neurofibromatosis. Radiology 1972; 103: 143–6
Racoceanu SN, Mendlowitz M, Suck AF,Wolf RL, Naftchi NE. Digital capillary blood flow in clubbing. 85 Kr studies in hereditary and acquired cases.Ann Intern Med 1971; 75: 933–5
Reeder MM. Reeder and Felson’s Gamut in radiology. Comprehensive lists of roentgen differential diagnosis. Springer,
New York Berlin Heidelberg, 1993 (3rd ed.), p. 224
Resnick D. Thyroid disorders. In: Resnick D (ed.) Diagnosis
of bone and joint disorders. W.B. Saunders Company,
Philadelphia, 1995 (3rd ed.), pp. 1995–2011
Resnick D, Niwayama G. Enostosis, hyperostosis, and periostitis. In: Resnick D (ed.) Diagnosis of bone and joint disorders. W.B. Saunders Company, Philadelphia, 1995b (3rd
ed.), pp. 4396–466
Resnick D, Niwayama G. Osteomyelitis, septic arthritis, and
soft tissue infection: mechanisms and situations. In:
Resnick D (ed.) Diagnosis of bone and joint disorders. W.B.
Saunders Company, Philadelphia, 1995a (3rd ed.), pp.
2325–418
Rimoin DL. Pachydermoperiostosis (idiopathic clubbing and
periostosis). Genetic and physiologic considerations. N
Engl J Med 1965; 272: 923–31
Rutherford RB, Rhodes BA, Wagner HN Jr. The distribution
of extremity blood flow before and after vagectomy in a
patient with hypertrophic pulmonary osteoarthropathy.
Dis Chest 1969; 56: 19–23
Seeger LL, Hewel KC,Yao L, Gold RH, Mirra JM, Chandnani VP,
Eckardt JJ. Ribbing disease (multiple diaphyseal sclerosis):
imaging and differential diagnosis. AJR Am J Roentgenol
1996; 167: 689–94
Sillero Garcia C, de Teresa Parreno L, Ivorra Miralles F, Pascual
Gomez E. Hypertrophic osteoarthropathy associated to
gastrointestinal disease: contribution of 2 new cases and
review of the literature. Rev Clin Esp 1978; 150: 367–71
Silverman FN. Virus diseases of bone. Do they exist? The Neuhauser Lecture. AJR Am J Roentgenol 1976; 126: 677–703
Spjut HJ, Dorfman HD. Florid reactive periostitis of the tubular bones of the hands and feet. A benign lesion which may
simulate osteosarcoma. Am J Surg Pathol 1981; 5: 423–33
Spranger JW, Langer LO, Wiedemann HR. Bone dysplasias. An
atlas of constitutional disorders of skeletal development.
W. B. Saunders Company, Philadelphia, 1974, p. 171
Steenbrugge F, Verstraete K, Poffyn B, Uyttendaele D, Verdonk
R. Recurrent massive subperiosteal hematoma in a patient
with neurofibromatosis. Eur Radiol 2001; 11: 480–3
Stern PJ, Lim EVA, Krieg JK. Giant metacarpal osteoma. A case
report. J Bone Joint Surg Am 1985; 67: 487–9
Taj-Eldin S, Al-Jawad J. Cortical hyperostosis: infantile and
juvenile manifestations in a boy. Arch Dis Child 1971; 46:
565–6
Tüysüz B, Mercimek S, Ungur S, Deniz M. Calcitonin treatment
in osteoectasia with hyperphosphatasia (juvenile Paget’s
disease): radiographic changes after treatment. Pediatr
Radiol 1999; 29: 838–41
Van Buskirk FW, Tampas JP, Peterson OS. Infantile cortical
hyperostosis: an inquiry into its familial aspects. AJR Am J
Roentgenol 1961; 85: 613–32
Abnormalities of the Shape and Contour of the Long Bones
Vanhoenacker FM, Pelckmans MC, de Beuckeleer LH, Colpaert
CG, de Schepper AM. Thyroid acropachy: correlation of imaging and pathology. Eur Radiol 2001; 11: 1058–62
Varan A, Kutluk T, Demirkazik FB, Akyuz C, Buyukpamukcu
M. Hypertrophic osteoarthropathy in a child with nasopharyngeal carcinoma. Pediatr Radiol 2000; 30: 570–2
Vogl A, Goldfischer S. Pachydermoperiostosis: primary or
idiopathic osteoarthropathy. Am J Med 1962; 33: 166–87
Worrall VT, Butera V. Sickle-cell dactylitis. J Bone Joint Surg
Am 1976; 58: 1161–3
Cortical Thinning
䉴 [Decrease in thickness of the cortex]
Thin cortices are among the radiographic stigmata of
osteoporosis, a pathologic state characterized by a net
decrease in the skeletal mass. The reader is referred to
Chapter 9, section entitled “Osteoporosis” for a more
detailed discussion of the pertinent disorders. This
section also shows remarkable overlap with others in
this book (see Chapter 2, sections “Slender, Fhin or
Twisted Ribs”, and “Slender Clavicles” and Chapter 9,
section: “Multiple Fractures, Fragile Bones”). In this
section, the fundamental radiographic and pathologic features of osteoporosis are summarized. Cortical
thinning in osteoporotic bones can be the result of either decreased production or increased resorption of
bone. Osseous resorption can take place at an endosteal, intracortical, or periosteal site. Endosteal resorption gives rise to irregularities of the inner margins of the cortex and widening of the medullary cavity. These findings are difficult to identify in the early
stages, as they also occur during normal bone remodeling (Resnick and Niwayama 1995). Moreover, they
are not specific, occurring in a number of different
conditions associated with osteoporosis, including
metabolic disorders and neoplasms, notably plasma
cell myeloma, leukemia, and lymphoma (Fitzpatrick
2002). On the other hand, localized scalloping or erosion of the inner cortex, which is often caused by isolated or multiple lesions exhibiting well-defined sclerotic margins, is easily differentiated from widespread endosteal resorption of metabolic origin.
Notable examples of focal inner cortical scalloping include bone cyst, chondroid lesions (enchondroma,
chondroblastoma, chondromyxoid fibroma, chondrosarcoma, periosteal chondroma), and cortical fibrous defect (Reeder 1993). Intracortical resorption
manifests with longitudinal radiolucent striations
within the cortex, which are most prominent in the
subendosteal zone. These striations are not visible on
routine radiography, their detection requiring magnification techniques. Intracortical radiolucent changes
299
indicate a high-bone-turnover state and can be seen
in hyperparathyroidism, hyperthyroidism, acromegaly, osteomalacia, renal osteodystrophy, disuse
osteoporosis, and reflex sympathetic dystrophy
(Resnick and Niwayama 1995). They are much less
common in low-bone-turnover states, such as senile
or postmenopausal osteoporosis and Cushing disease. Subperiosteal resorption also typically occurs in
high-bone-turnover states, especially hyperparathyroidism, and provokes irregularities of the cortical
outer margins (Resnick and Niwayama 1995). Less
commonly, subperiosteal bone resorption occurs in
association with disseminated lipogranulomatosis,
mucolipidosis, GM1 gangliosidosis, severe rickets,
and subperiosteal osteomyelitis or hematoma. A
number of additional lesions can cause destruction or
erosion of the external surface of the bone, including
vascular aneurysm or AV fistula, gouty tophus, fibrous
cortical defect, cortical desmoid, neoplasms (primary
bone neoplasm, hemangioma, neurofibroma, glomus
tumor, giant cell tumor of tendon sheath, leukemia,
lymphoma, lung carcinoma, neuroblastoma, metastasis) and, in the juxta-articular region, rheumatoid
arthritis and amyloidosis (Reeder 1993). Because of
the association with osteoporosis, cortical thinning is
almost always accompanied by reduction of the cancellous bone. The radiographic patterns of decreased
spongiosa in the tubular bones differ according to the
underlying pathologic process and patient age. A diffuse pattern consisting of homogeneous or spotty radiolucent areas is more characteristic of senile or
postmenopausal osteoporosis. A metaphyseal pattern, with band-like radiolucent areas, is more commonly seen in children and may simulate bone infection.A pattern of very little spongiosa in the subchondral and periarticular region, with linear, band-like,
or spotty radiolucent areas, may be detectable in reflex sympathetic dystrophy and immobilization states
(Resnick and Niwayama 1995). When severe, this pattern can simulate erosive inflammatory or infectious
osteoarthritis.
The cortices in the long bones are abnormally thin
in osteogenesis imperfecta type I (OMIM 166200) and
type IV (OMIM 166220), hypophosphatasia (OMIM
241500) (Fallon et al. 1984), homocystinuria (OMIM
236200) (Smith 1967), gracile bone dysplasias (OMIM
602361), and disorders with a senile-type appearance, including progeria (OMIM 176670), Cockayne
syndrome (OMIM 216400), and Hallermann-Streiff
syndrome (OMIM 234100).
Hyperparathyroidism is a general term indicating
abnormally high levels of parathyroid hormone in
the blood. Alterations of parathyroid function cause
a breakdown in calcium homeostasis, giving rise to
300
Chapter 5 · Long Bones
Fig. 5.23 a–d. Hyperparathyroidism in a boy: a, b preoperative radiographs at
a 3 months and b 2 months of
age. Note generalized osteoporosis, extensive periosteal
resorption with indistinctness of the cortices, and severe rachitic changes at the
metaphyses, with fraying and
irregularities. c, d At 18
months after surgical removal
of the patient’s pa-rathyroid
glands there is improved bone
mineralization and cortical
formation, attenuation of the
rachitic changes, and repair of
the fibular fracture. (From
Doria et al. 2002)
a
b
c
d
Abnormalities of the Shape and Contour of the Long Bones
characteristic pathological and radiographic abnormalities (Genant et al. 1973). The pathological hallmark of the condition is resorption of osseous tissue,
either at the surface of bone trabeculae or at the cortical level. Histologically, there is increased activity of osteoclasts and inhibition of osteoblastic collagen formation, resulting in bone resorption and inadequate new
bone formation. As bone resorption proceeds, substitutive fibrosis takes place, to the extent of the severe
changes of osteitis fibrosa cystica, in which fibrosis alternates with bony cysts and brown tumors. As anticipated, cortical bone resorption can occur at the endosteal, intracortical or subperiosteal location, the latter being virtually pathognomonic for the condition.
Cortices are thinned and rarefied, and trabeculae are
distorted and blurred (Fig. 5.23a–d). Although these
findings are widespread, they are more easily detectable in the tubular bones of the hands, especially
when industrial films and magnification techniques
are used (Nielsen 2001). Fractures and deformities can
be seen. Thin, indistinct cortices in the bones of the appendicular skeleton are characteristic of fibrogenesis
imperfecta ossium, a disorder with no apparent hereditary factor, manifesting in adult life with progressive
skeletal pain, muscle weakness and atrophy, and high
levels of serum alkaline phosphatase. Histopathological features are those of a collagen defect causing osteomalacia, including abnormally thin and disorganized collagen fibrils, absent lamellar collagen, and replacement of lamellar bone with abnormally thick and
poorly calcified osteoid matrix (Frame et al. 1971). On
radiograms,coarsened,indistinct trabeculae with mottled areas of increased bone density are seen, as are
very thin cortices (Stoddart et al. 1984).
Radiographic Synopsis
AP and lateral projections. Information on the status
of periosteal and endosteal bone formation and resorption can be derived from high-quality, magnified
radiographs of the hand. To quantitate the degree of
cortical resorption, radiographic morphometry is
used, as follows. The midpoint of the entire length of
the 2nd metacarpal is found, and a line is drawn across
the shaft. Along this line, the outer diameter (width of
the bone), the marrow cavity (width of the marrow
cavity), and the combined cortical thickness can be
measured. Standard norms for children and adults are
available (Garn et al. 1967; Morgan et al. 1967).
1. Lacy, spiculated contour of the tubular bones, especially in the hands; tuftal resorption; intracortical radiolucent linear striations; scalloped defects
along the inner border of the cortex; cortical thinning; trabecular resorption with granular appear-
301
ance of the medullary cavity; cystic changes;
brown tumors (hyperparathyroidism)
2. Coarse, indistinct trabeculae interspersed with
patchy areas of increased bone density; very thin,
evanescent cortices (fibrogenesis imperfecta ossium)
Associations
• Anemias, primary (thalassemia, sickle cell anemia)
• Cockayne syndrome
• Fibrogenesis imperfecta ossium
• Fibrous dysplasia
• Gaucher’s disease
• GM1 gangliosidosis
• Gracile bone dysplasia
• Hallermann-Streiff syndrome
• Histiocytosis X
• Homocystinuria
• Hyperparathyroidism
• Hyperphosphatasemia
• Hypophosphatasia
• Membranous lipodystrophy
• Menkes’ kinky hair syndrome
• Metaphyseal dysplasia (Pyle disease)
• Metastasis
• Multiple myeloma
• Niemann-Pick disease
• Osteogenesis imperfecta, type I and IV
• Osteoporosis, all types
• Osteoporosis, idiopathic juvenile
• Progeria
• Singleton-Merten syndrome
• Stickler syndrome
• Winchester syndrome
References
Doria AS, Huang C, Makitie O, Thorner P, Kooh SW, Sochett E,
Daneman A. Neonatal, severe primary hyperparathyroidism: a 7-year clinical and radiological follow-up of one
patient. Pediatr Radiol 2002; 32: 684-9
Fallon MD, Teitelbaum SL, Weinstein RS, Goldfischer S, Brown
DM, Whyte MP. Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. Medicine 1984; 63: 12–24
Fitzpatrick LA. Secondary causes of osteoporosis. Mayo Clin
Proc 2002; 77: 453–68
Frame B, Frost HM, Pak CY, Reynolds W, Argen RJ. Fibrogenesis imperfecta ossium. A collagen defect causing osteomalacia. N Engl J Med 1971; 285: 769–72
Garn SM, Rohmann CG, Silverman FN. Radiographic standards for postnatal ossification and tooth calcification. Med
Radiogr Photogr 1967; 43: 45–66
Genant HK, Heck LL, Lanzl LH, Rossmann K, Horst JV, Paloyan E. Primary hyperparathyroidism. A comprehensive
study of clinical, biochemical and radiographic manifestations. Radiology 1973; 109: 513–24
302
Chapter 5 · Long Bones
Morgan DB, Spiers FW, Pulvertaft CN, Fourman P. The amount
of bone in the metacarpal and the phalanx according to age
and sex. Clin Radiol 1967; 18: 101–8
Nielsen SP. The metacarpal index revisited: a brief overview.
J Clin Densitom 2001; 4: 199–207
Reeder MM. Reeder and Felson’s gamut in radiology. Comprehensive lists of roentgen differential diagnosis. Springer,
New York Berlin Heidelberg, 1993 (3rd ed.), pp. 227–8
Resnick D, Niwayama G. Osteoporosis. In: Resnick D (ed.)
Diagnosis of bone and joint disorders. W.B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 1783–853
Smith SW. Roentgen findings in homocystinuria. Am J
Roentgenol Radium Ther Nucl Med 1967; 100: 147–54
Stoddart PG, Wickremaratchi T, Hollingworth P, Watt I. Fibrogenesis imperfecta ossium. Br J Radiol 1984; 57: 744–51
Limb Shortening
Limb shortening can result from reduced length of
each of the individual bones in the limb, singly or in
variable combination.
This chapter encompasses two specific types of
limb shortening: shortening of the proximal segments, such as humerus and femur (rhizomelia), and
shortening of the mid-portion segments, such as radius/ulna and tibia/fibula (mesomelia). Since shortening is only rarely completely selective within the
limb, the terms rhizomelia and mesomelia are intended to refer to a gross disproportion in the shortening between the proximal and middle segments in
the limb. Moreover, varying degrees of upper and
lower limb involvement are sometimes seen in the
same patient. Recognition of a given pattern of limb
shortening, e.g., rhizomelic or mesomelic, decreases
the range of diagnostic possibilities. More specific
defects in the limbs, including Madelung deformity,
tibial and fibular hemimelia, and radial and ulnar ray
deficiency are addressed in other sections of this
chapter and elsewhere in the book.
Rhizomelic Limb Shortening
䉴 [Shortening of the proximal segments
of the extremities (humerus, femur)]
By far the most common form of rhizomelic limb
shortening is seen in patients with achondroplasia
(OMIM 100800), an autosomal dominant disorder
with complete penetrance. Although shortening can
affect any of the tubular bones, including those in the
hands and feet, in patients of all ages, it is most prominent in the proximal segments, especially those of the
upper extremities (humerus more involved than femur). In infancy, the proximal femur and humerus
have a characteristic appearance of oval areas of lucency, while the distal femur is medially slanted, owing
to defective or delay ossification of the lateral femoral
condyle. In later years, abnormalities of the distal femur include metaphyseal flaring, a V-shaped appearance, small epiphysis, and a ball-in-socket epiphyseal
configuration (Langer et al. 1967). These radiographic
changes are noticeably more severe in early lethal homozygous achondroplasia, an exceedingly rare skeletal
dysplasia that shares similarities with thanatophoric
dysplasia (Langer et al. 1969). In pseudoachondroplasia (OMIM 177170) the body proportions resemble
those of achondroplasia, with a long trunk and short
extremities, the proximal segments being primarily
affected. It differs from achondroplasia in that the
skull is not affected and clinical manifestations are not
present at birth, not developing until the 2nd year of
life or later (Heselson et al. 1977). Additional distinguishing features include epiphyseal dysplasia, metaphyseal widening and irregularities, the type of vertebral alterations (short pedicles with posterior scalloping in achondroplasia; marked end-plate irregularities
and central tongue-like protrusions in pseudoachondroplasia), and a specific pelvic appearance (round iliac bones, flat acetabula, narrow sciatic notches in
achondroplasia; markedly irregular pubic and ischial
bones in pseudoachondroplasia). Partial restoration
of normal vertebral shape occurs during adolescence.
The capital femoral epiphyses are small and irregular
and are followed by early osteoarthritis in adults.
Chondrodysplasia punctata, rhizomelic type (OMIM
215100) features severe shortening and metaphyseal
splaying of the proximal segments of the extremities.
Calcific stippling of hyaline cartilage is seen at the
ends of the humeri and femurs, adjacent to the spine
and pubic/ischial bones, near the patellas and ribs, and
in the carpal and tarsal bones. In contrast to the Conradi-Hünermann type of chondrodysplasia punctata,
the stippling has a symmetrical distribution (Gilbert
et al. 1976). Severe metaphyseal splaying of the humeri
and femurs, coronal clefts in the spine, symmetrical
shortening of metacarpals (especially the 4th), and
hypoplastic distal phalanges are additional characteristic features of the rhizomelic type of chondrodysplasia punctata (Silengo et al. 1980). Opsismodysplasia (OMIM 258480) is a very rare autosomal recessive dwarfing disorder characterized by rhizomelic micromelia with marked metaphyseal flaring
and cupping, and severe platyspondyly with hypoplastic or absent vertebral bodies and normally ossified
posterior elements (Maroteaux et al. 1984). The epiphyseal appearance is severely retarded. Additional
features include narrow thorax with short ribs, very
Limb Shortening
b
a
Fig. 5.24 a–c. Omodysplasia, autosomal recessive, in a newborn girl. a Note severe limb
shortening, with predominant involvement
of the proximal segments (rhizomelic
dwarfism). Note also bilateral pterygia in the
upper extremities. The face is flat, with short
upturned nose and long philtrum; the nipples are widely spaced. b Severe shortening
of the humerus, radio-ulnar diastasis, and
flared metaphyses. c Severe shortening of
the femora, with clubbed upper ends, and
short lower legs, with tibias shorter than
fibulas. (From Masel et al. 1998)
short tubular bones in the hands, and unossified skull
base (Zonana et al. 1977). Omodysplasia (OMIM
164745), a term introduced by Maroteaux in 1989
(Maroteaux et al. 1989), is used to mean a type of skeletal dysplasia with a characteristic facies (flat face, depressed nasal bridge, long philtrum, large ears), severe
rhizomelic limb shortening (especially involving the
humeri), and radioulnar diastasis at the elbows. The
humeri are short, with hypoplasia of their distal portion and anterior dislocation of the radial head at the
elbow. The femurs are also short, with club-shaped
proximal ends (Fig. 5.24a–c). Occasional findings include low-set, widely spaced nipples, inguinal hernias,
microphthalmia, micrognathia, maxillary hypoplasia,
and brachycephaly. Inheritance can be either autosomal dominant or autosomal recessive (OMIM
258315), the latter with generalized involvement of the
303
c
limbs and severe dwarfism (Baxova et al. 1994; Al
Gazali and Al-Asaad 1995). Femorofacial syndrome
(OMIM 134780) is a rare association of bilateral
femoral hypoplasia/aplasia and a characteristic facies
with short nose and elongated philtrum, thin upper
lip, micrognathia, upslanting palpebral fissure, cleft
palate, and ear deformities. Hypoplasia of the femur at
one side can occur in association with absence of the
contralateral femur. The acetabula are hypoplastic.
Short humeri, short or hypoplastic fibulas, radiohumeral or radioulnar synostosis, Sprengel deformity,
rib anomalies, vertebral anomalies, foot deformities,
and renal, cardiovascular, and gastrointestinal anomalies are additional features (Daentl et al. 1975). The
inheritance pattern is unknown. This syndrome is
clearly separate from proximal femoral focal deficiency, a relatively common, unilateral skeletal anomaly
304
Chapter 5 · Long Bones
that occurs as an isolated defect. Cranio-ecto-dermal
dysplasia (Sensenbrenner syndrome, OMIM 218330) is
an autosomal recessive condition characterized by defects of ectoderm-derived structures and characteristic
bone anomalies, notably dolichocephaly and rhizomelia. Growth deficiency, sparse fine hair, delayed psychomotor development, microcephaly, photophobia,
short thorax, heart defect, chronic renal failure, and abnormal calcium homeostasis are inconsistent manifestations (Amar et al. 1997; Levin et al. 1977). Weisenbacher-Zweymuller syndrome (OMIM 277610), which now is
recognized to be the same as the heterozygous form of
OSMED (nonocular type III Stickler syndrome, OMIM
184840), is characterized by a neonatal type of rhizomelic dwarfism with neonatal micrognathia and metaphyseal widening of the long bones and vertebral coronal clefts. Regression of bone changes with catch-up
growth in the subsequent 2–3 years is a striking manifestation (Chemke et al. 1992).
Rhizomelia has been reported in association with
variable skeletal and nonskeletal defects (Verloes et
al. 1997; Faye-Petersen et al. 1991; Urbach et al. 1986).
Radiographic Synopsis
AP and lateral projections.
1. Rhizomelic limb shortening (humerus >femur);
oval lucent proximal portions of femur and
humerus (in infancy); distal femur medial slanting (in infancy) and metaphyseal flaring (in childhood) (achondroplasia)
2. Rhizomelic limb shortening; small and irregular
capital femoral epiphyses; epiphyseal dysplasia;
metaphyseal widening and irregularities (pseudoachondroplasia)
3. Severe rhizomelic limb shortening; metaphyseal
splaying; calcific stippling (chondrodysplasia
punctata, rhizomelic type)
4. Rhizomelic micromelia; marked metaphyseal flaring and cupping (opsismodysplasia, Weissenbacher-Zweymuller syndrome)
5. Bilateral femoral hypoplasia/aplasia; short humeri
(femorofacial syndrome)
Associations
• Achondroplasia
• Atelosteogenesis
• Chondrodysplasia punctata, rhizomelic type
• Femoral dysplasia
• Femorofacial syndrome
• Omodysplasia
• Opsismodysplasia
• Pseudoachondroplasia
• Weissenbacher-Zweymuller syndrome
References
Al Gazali LI, Al-Asaad FA. Autosomal recessive omodysplasia.
Clin Dysmorph 1995; 4: 52–6
Amar MJ, Sutphen R, Kousseff BG. Expanded phenotype of
cranioectodermal dysplasia (Sensenbrenner syndrome).
Am J Med Genet 1997; 70: 349–52
Baxova A, Maroteaux P, Barosova J, Netriova I. Parental consanguinity in two sibs with omodysplasia. Am J Med Genet
1994; 49: 263–5
Chemke J, Carmi R, Galil A, Bar-Ziv Y, Ben-Ytzhak I, Zurkowski L.Weissenbacher-Zweymuller syndrome: a distinct autosomal recessive skeletal dysplasia. Am J Med Genet 1992;
43: 989–95
Daentl DL, Smith DW, Scott CI, Hall BD, Gooding CA. Femoral
hypoplasia-unusual facies syndrome. J Pediatr 1975; 86:
107–11
Faye-Petersen OM, Ward K, Carey JC, Knisely AS. Osteochondrodysplasia with rhizomelia, platyspondyly, callosal agenesis, thrombocytopenia, hydrocephalus, and hypertension.
Am J Med Genet 1991; 40: 183–7
Gilbert EF, Opitz JM, Spranger JW, Langer LO Jr, Wolfson JJ,
Viseskul C. Chondrodysplasia punctata-rhizomelic form.
Pathologic and radiologic studies of three infants. Eur J
Pediatr 1976; 123: 89–109
Heselson NG, Cremin BJ, Beighton P. Pseudoachondroplasia, a
report of 13 cases. Br J Radiol 1977; 50: 473–82
Langer LO Jr, Baumann PA, Gorlin RJ.Achondroplasia.AJR Am
J Roentgenol 1967; 100: 12–26
Langer LO Jr, Spranger JW, Greinacher I, Herdman RC. Thanatophoric dwarfism. A condition confused with achondroplasia in the neonate, with brief comments on achondrogenesis and homozygous achondroplasia. Radiology
1969; 92: 285–94
Levin LS, Perrin JCS, Ose L, Dorst JP, Miller JD, McKusick VA. A
heritable syndrome of craniosynostosis, short thin hair,
dental abnormalities, and short limbs: cranioectodermal
dysplasia. J Pediatr 1977; 90: 55–61
Maroteaux P, Stanescu V, Stanescu R, Le Marec B, Moraine C,
Lejarraga H. Opsismodysplasia: a new type of chondrodysplasia with predominant involvement of the bones of the
hand and the vertebrae. Am J Med Genet 1984; 19: 171–82
Maroteaux P, Sauvegrain J, Chrispin A, Farriaux JP. Omodysplasia. Am J Med Genet 1989; 32: 371–5
Masel JP, Kozlowski K, Kiss P. Autosomal recessive omodysplasia: report of three additional cases. Pediatr Radiol 1998; 28:
608–11
Silengo MC, Luzzatti L, Silverman FN. Clinical and genetic
aspects of Conradi-Hunermann disease. A report of three
familial cases and review of the literature. J Pediatr 1980;
97: 911–7
Urbach D, Hertz M, Shein M, Goodman RM, Shine M. A new
skeletal dysplasia syndrome with rhizomelia of the humeri
and other malformations. Clin Genet 1986; 29: 83–7
Verloes A, Lesenfants S, Misson JP, Galand A, Koulischer L.
Microcephaly, muscular build, rhizomelia, and cataracts:
description of a possible recessive syndrome and some
comments on the use of electronic databases in syndromology. Am J Med Genet 1997; 68: 455–60
Zonana J, Rimoin DL, Lachman RS, Cohen AH. A unique chondrodysplasia secondary to a defect in chondroosseous
transformation. Birth Defects Orig Art Ser 1977; 13: 155–63
Limb Shortening
Mesomelic Limb Shortening
䉴 [Shortening of the middle segments
of the extremities (radius and ulna;
tibia and fibula)]
The most common form of mesomelic dwarfism is
X-linked dominant dyschondrosteosis (Léri-Weill
syndrome, OMIM 127300), a condition manifesting
in late childhood and affecting female more frequently and more severely than male subjects. Varying degrees of Madelung deformity and mild shortening of the fibula and tibia, with prominence of its
medial portion, are characteristic features (Fig.
5.25a,b). Genu valgum, coxa valga, and shortening of
the tubular bones in the hands and feet can be additional features (Herdman et al. 1966). Mesomelic dysplasia, Langer type (OMIM 249700) is due to homozygous deletion or point mutation of the SHOX
gene, which causes dyschondrosteosis in the heterozygous state. Short limbs with mesomelic micromelia and hypoplastic mandible are major clinical
features. The distal portion of the ulna is hypoplastic,
and the radius is short and wide with dorsolateral
bowing and tilting of its end-portion towards the ulna. The hand is deviated toward the ulna. The tibia is
short and wide, with metaphyseal flaring. The fibula
is proximally deficient (Langer 1967). The autosomal
dominant mesomelic dysplasia, Nievergelt type
(OMIM 163400) is the most severe form of mesomelic dysplasia. Bones in the shanks are markedly hypoplastic and deformed, with rhomboid or triangular configuration of the tibia. The fibula is involved to
a lesser extent. Occasionally, the bones in the forearm
are also affected, the radius displaying more severe
shortening and widening than the ulna. Proximal radioulnar synostosis and, in later years, tarsal synostosis are distinguishing features (Young and Wood
1975). The unique rhomboidal shape of the tibia and
fibula helps differentiate this condition from recessive mesomelic dwarfism, Langer type, and from
Grebe chondrodysplasia (OMIM 200700), an autosomal recessive disorder characterized by normal axial
skeleton and skull and severely shortened and deformed limbs, with a proximal–distal gradient of
severity (Costa et al. 1998). Mesomelic dysplasia,
Werner type (OMIM 188770) is an autosomal dominant disorder with bilateral tibial hypoplasia/aplasia.
The forearm is usually not affected. Absence of the
thumb and polydactyly or syndactyly of the hands
and feet are additional features (Pashayan et al.
1971). A lethal autosomal recessive form of the disease has been described (Kozlowski and Ekof 1987).
305
Ulnofibular dysplasia, Rheinhardt-Pfeiffer type
(OMIM 191400), which has an autosomal dominant
inheritance, is another dwarfing disorder presenting
at birth with mesomelic brachymelia. There is distal
shortening of the ulna, bowing of the radius, and
volar dislocation of the radial head. The fibula is
proximally deficient, expanded at mid-shaft, and laterally angulated, with a cutaneous dimple at the apex
of the angulation (Rheinhardt and Pfeiffer 1967). Hypoplasia of the lateral aspect of the distal tibia, with
lateral tilting of the talus, is also a feature. Mild cases
of the Nievergelt type of mesomelic dysplasia and
Rheinhardt-Pfeiffer dysplasia may be difficult to differentiate, both clinically and radiologically. Mesomelic dwarfism, hypoplastic tibia-radius type
(OMIM 156230) features bilateral hypoplasia/aplasia
of the tibia and radius, elongated fibula, and shortening of the lower legs. Tibial pseudarthrosis may be
seen. Additional findings include absent thumbs,
polydactyly, aplasia of the patella, and varying degrees of metatarsal and phalangeal hypoplasia (Leroy
1975). Mesomelic brachymelia, with prominent involvement of the forearms, occurs in Robinow syndrome (‘fetal face’ syndrome, OMIM 180700). Hypoplasia of the distal ulna and dislocation of the radial head are present. Craniofacial dysmorphism (large
neurocranium), genital hypoplasia, and abnormalities in the hands (clefting of the distal phalanx in the
thumb, clinodactyly of the 5th finger) are additional
features (Robinow et al. 1969). Severe costovertebral
segmentation defects with mesomelia are distinguishing features of the autosomal recessive COVESDEM syndrome (OMIM 268310). Acromesomelic dysplasia Maroteaux type (OMIM 602875) is a rare autosomal recessive disorder characterized by mesomelic
brachymelia and shortening of hands and feet. The
involved gene(s) has(have) been mapped to 9p13p12 (Kant et al. 1998). Affected patient are dwarves,
with short distal limbs and a disproportionately large
head. The radius is short and curved, the ulna is distally deficient, and the tubular bones in the hands
and feet are very short, broad, and stubby. Coneshaped epiphyses develop.A relatively large great toe,
with wide proximal and distal phalanges, are occasionally seen (Langer et al. 1977). Additional features
are posteriorly deficient vertebral bodies, curved
clavicles, metaphyseal flaring of long tubular bones,
and hypoplasia of the basilar portions of the ilia. It
has been shown that the Maroteaux type and the
Campailla-Martinelli type of acromesomelic dysplasia represent different manifestations of the same
disorder (Kant et al. 1998). Severe acromelia, scaphocephaly, and elbow contracture are more typical of
306
Chapter 5 · Long Bones
b
a
Fig. 5.25 a, b. Upper limb brachymesomelia in a woman patient. There is shortening of the radius and ulna (radius shorter than ulna) and dorsal subluxation of distal ulna, a pattern reminiscent of the Madelung deformity. However, severe deficiency and dislocation of the radial head, lack of radial bowing, and absent triangularization of distal radial epiphysis and carpal bones militate against Madelung
deformity. The patient had no other remarkable abnormalities, and the bones in
the shanks (not shown) were normal
the Maroteaux type, whereas vertebral anomalies,
scoliosis, and shortening of the 4th and 5th
metatarsals and 2nd and 3rd phalanges are characteristic of the Campailla-Martinelli type (Kaitila et
al. 1976). A similar disorder, with manifestations
closely resembling those of Grebe chondrodysplasia,
is referred to as acromesomelic dys-plasia, HunterThompson type (OMIM 201250). Features in this type
are more severe, including marked hypoplasia or
aplasia of several bony elements in the hands and
feet, but the axial skeleton is not involved. The
Hunter-Thompson type of acromesomelic dysplasia
and Grebe chondrodys-plasia are allelic disorders,
caused by mutations in cartilage-derived morphogenetic protein (CDMP1) located at 20q11.2
(Thomas et al. 1996). Heterozygous mutations in the
CDMP1 gene may cause the autosomal dominant
brachydactyly type C (Polin-kovsky et al. 1997).
Acromesomelic brachymelia also occurs in chondroectodermal dysplasia (Ellis-van Creveld syndrome, OMIM 225500), an autosomal recessive
dwarfing disorder with hand polydactyly, hamatecapitate fusion, and heart defects (Taylor et al. 1984).
Radiographic Synopsis
AP and lateral projections
1. Madelung deformity; mild shortening of fibula
and tibia (dyschondrosteosis)
2. Hypoplastic distal ulna; short, bowed radius; ulnar
deviation of the hand; short, wide tibia; hypoplastic proximal fibula (mesomelic dysplasia, Langer
type)
3. Rhomboid or triangular tibia; short fibula; proximal radioulnar synostosis; tarsal synostosis (mesomelic dysplasia, Nievergelt type)
4. Tibial hypoplasia/aplasia; absent thumb; polydactyly or syndactyly (mesomelic dysplasia, Werner type)
5. Hypoplastic distal ulna; bowed radius, with proximal dislocation; lateral angulation of fibula; lateral tilting of the tibiotarsal articulation (ulnofibular
dysplasia)
6. Bilateral hypoplasia/aplasia of tibia and radius;
relatively long fibula (mesomelic dwarfism, hypoplastic tibia-radius type)
7. Forearms most involved; hypoplasia of distal ulna;
radial head dislocation; bifid distal phalanx of
the thumb; 5th finger clinodactyly (Robinow syndrome)
Abnormalities of the Long Bones in the Upper Extremities
8. Short, curved radius; deficient distal ulna; short,
broad, stubby tubular bones in hands and feet;
large great toe; cone-shaped epiphyses (acromesomelic dysplasia)
9. Acromesomelic brachymelia; polydactyly; hamatecapitate fusion (chondroectodermal dysplasia)
Associations
• Acromesomelic dysplasias
• Aminopterin embryopathy syndrome
• Chondroectodermal dysplasia
(Ellis-van Creveld)
• Chromosome 18 trisomy syndrome (Edwards)
• COVESDEM syndrome
• Dyschondrosteosis
• Facio-cardio-melic dysplasia, lethal
• Mesomelia-synostoses syndrome
• Mesomelic dwarfism, hypoplastic tibiaradius type
• Mesomelic dysplasia, Kantaputra type
• Mesomelic dysplasia, Langer type
• Mesomelic dysplasia, Nievergelt type
• Mesomelic dysplasia, Werner type
• Robinow syndrome
• Schinzel-Giedion syndrome
• Ulnofibular dysplasia
(Rheinhardt-Pfeiffer type)
References
Costa T, Ramsby G, Cassia F, Peters KR, Soares J, Correa J,
Quelce-Salgado A, Tsipouras P. Grebe syndrome: clinical
and radiographic findings in affected individuals and heterozygous carriers. Am J Med Genet 1998; 75: 523–9
Herdman RC, Langer LO, Good RA. Dyschondrosteosis. The
most common cause of Madelung’s deformity. J Pediatr
1966; 68: 432–41
Kaitila II et al. Mesomelic skeletal dysplasias. Clin Orthop
1976; 114: 94–106
Kant SG, Polinkovsky A, Mundlos S, Zabel B, Thomeer RTWM,
Zonderland HM, Shih LY, van Haeringen A, Warman ML.
Acromesomelic dysplasia Maroteaux type maps to human
chromosome 9. Am J Hum Genet 1998; 63: 155–62
Kozlowski K, Eklof O. Werner mesomelic dysplasia. J Belge
Radiol 1987; 70: 337–9
Langer LO Jr. Mesomelic dwarfism of the hypoplastic ulna,
fibula, mandible type. Radiology 1967; 89: 654–60
Langer LO, Beals RK, Solomon IL, Bard PA, Bard LA, Rissman
EM, Rogers JG, Dorst JP, Hall JP, Sparkes RS, Franken EA.
Acromesomelic dwarfism: manifestations in childhood.
Am J Med Genet 1977; 1: 87–100
Leroy J. Dominant mesomelic dwarfism of the hypoplastic
tibia, radius type. Clin Genet 1975; 7: 280–5
Pashayan H, Fraser FC, McIntyre JM, Dunbar JS. Bilateral aplasia of the tibia, polydactyly and absent thumbs in father
and daughter. J Bone Joint Surg Br 1971; 53: 495–9
307
Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, Reardon W, Kant SG, Brunner HG, van der Burgt I,
Chitayat D, McGaughran J, Donnai D, Luyten FP, Warman
ML. Mutations in CDMP1 cause autosomal dominant
brachydactyly type C. Nat Genet 1997; 17: 18-9
Rheinhardt K, Pfeiffer RA. Ulno-fibuläre Dysplasie. Eine autosomal-dominant vererbte Mikromesomelie ähnlich dem
Nievergelts-Syndrom. Fortschr Roentgenstr 1967; 107:
379–84
Robinow M, Silverman FN, Smith HD. A newly recognized
dwarfing syndrome. Am J Dis Child 1969; 117: 645–51
Taylor GA, Jackman AL, Calvert AH, Harrup KR. Polycarpaly
and other abnormalities of the wrist in chondroectodermal
dysplasia: the Ellis-van Creveld syndrome. Radiology 1984;
151: 393–6
Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J,
Luyten FP. A human chondrodysplasia due to a mutation in
a TGF-beta superfamily member. Nat Genet 1996; 12: 315-7
Young LW, Wood BP. Nievergelt syndrome. Birth Defects Orig
Art Ser 1975; 11: 81–5
Abnormalities of the Long Bones
in the Upper Extremities
Limb malformations can be classified as reduction
(deficiencies), excess, and fusion or segmentation
deformities. The last often occur in association with
reduction deformities. A more complete classification system includes the following categories: (I) failure of formation of parts; (II) failure of differentiation (separation) of parts; (III) duplication; (IV)
overgrowth; (V) undergrowth; (VI) congenital constriction band syndrome; and (VII) generalized
skeletal abnormalities (Swanson 1976).
The prevalence of babies born with upper limb
anomalies has been reported as approximately 1 in
500 (Giele et al. 2001). The most common anomalies
are failures of differentiation (35%), followed by duplications (33%), failures of formation (15%), generalized skeletal abnormalities (9.3%), congenital constriction bands (6.5%), undergrowth defects (4.3%),
and overgrowth defects (0.5%) (Giele et al. 2001;
Cheng et al. 1987). Deformities resulting from failure
of formation of parts (group I) are subclassified by
extent into complete (aplasia) and partial (hypoplasia) and by orientation into transverse and longitudinal (Kay 1974; Kay et al. 1975). Either an entire bone
or a part of it may fail to form, leading to a variety of
congenital deficiencies. In order of descending frequency, the fibula, the radius, the femur, the ulna, and
the humerus are most commonly involved (Mital
1976). Transverse limb deficiencies encompass those
congenital anomalies in which all skeletal elements
are absent distally along a given axis. This designation applies to the following defects: absence of the
308
Chapter 5 · Long Bones
In this section, the segmentation defects involving
the upper limbs and Madelung deformity are reviewed. Radial and ulnar reduction anomalies (hypoplasia/aplasia) and some common forms of excess
malformations, including gigantism and duplication
of individual bones, are discussed in Chapter 6.
References
Fig. 5.26. Four-limb amelia in a newborn. There is complete
absence of all bony components in the four limbs. The child’s
mother had been exposed to thalidomide during the first
trimester of pregnancy
entire limb (amelia); absence of the mesomelic and
acromelic portion of the limb (complete hemimelia);
absence of the hand/foot (acheiria/apodia); and absence of fingers/toes (adactyly). The category of longitudinal deficiency embraces all other deficiencies, including absence of the proximal and middle portions
of the limb with a well-formed hand/foot inserted at
the limb root (phocomelia); absence of the radius/tibia (radial/tibial hemimelia); absence of the ulna/fibula
(ulnar/fibular hemimelia); and absence of the central
rays of the hand/foot (split hand/foot). The causes of
reduction deformities can be genetic or environmental. The spectrum of malformations induced by maternal ingestion of thalidomide, an antipyretic and sedative drug, in early pregnancy (Diggle 2001) is well
known, ranging from mild hypoplasia of the first
metacarpal to severe limb reduction deformities, including phocomelia and complete four-limb amelia
(Fig. 5.26). The preaxial bones (radius, thumb, and index finger; femur, tibia, and first toes) are most commonly involved, and the upper extremities are more
commonly involved than the lower extremities
(McBride 1977; Quibell 1981; Jones 1994). Reduction
deformities can also be caused by deprivation of factors essential for normal development, such as maternal riboflavin deficiency (Kalter 1990).
Cheng JC, Chow SK, Leung PC. Classification of 578 cases of
congenital upper limb anomalies with the IFSSH system – a
10 years’ experience. J Hand Surg Am 1987; 12: 1055–60
Diggle GE. Thalidomide: 40 years on. Int J Clin Pract 2001; 55:
627–31
Giele H, Giele C, Bower C, Allison M. The incidence and epidemiology of congenital upper limb anomalies: a total population study. J Hand Surg Am 2001; 26: 628–34
Jones GR. Thalidomide: 35 years on and still deforming. Lancet
1994; 343: 1041
Kalter H. Analysis of the syndrome of congenital malformations induced in genetically defined mice by acute riboflavin deficiency. Teratog Carcinog Mutagen 1990; 10:
385–97
Kay HW. A proposed international terminology for the classification of congenital limb deficiencies. Orthot Prosth 1974;
28: 33–44
Kay HW, Day HJ, Henkel HL, Kruger LM, Lamb DW, Marquardt
E, Mitchell R, Swanson AB, Willert HG. The proposed international terminology for the classification of congenital
limb deficiencies. Dev Med Child Neurol 1975; 34: 1–12
McBride WG. Thalidomide embryopathy. Teratology 1977; 16:
79–82
Mital MA. Limb deficiencies: classification and treatment.
Orthop Clin North Am 1976; 7: 457–64
Quibell EP. The thalidomide embryopathy. An analysis from
the UK. Practitioner 1981; 225: 721–6
Swanson AB. A classification for congenital limb malformations. J Hand Surg Am 1976; 1: 8–22
Radioulnar Synostosis
䉴 [Proximal fusion between radius and ulna]
Radioulnar synostosis is the most common congenital segmentation defect in the long bones. Two main
types of radioulnar synostosis are recognized: (a)
proximal synostosis, consisting of smooth osseous
fusion of 2–6 cm of the proximal segments of radius
and ulna, with absent radial head; and (b) synostosis
involving the parts of the two bones just distal to the
proximal radial epiphysis, with radial head dislocation (Cleary and Omer 1985; Mital 1976; Bauer and
Jonsson 1988) (Fig. 5.27a,b).Varying degrees of limited forearm pronation occur in both types. Pain can be
an additional clinical complaint. Fusion between the
Abnormalities of the Long Bones in the Upper Extremities
309
b
a
Fig. 5.27 a, b. Radioulnar synostosis. a In a 2-year-old girl; note proximal
fusion between radius and ulna, radial head dislocation, and bowing deformity of the radius. b In a young adult: bilateral radioulnar synostosis
just distal to the well-formed radial heads and bilateral radial head dislocation
two bones can be either fibrous or osseous. The
stages through which the synostosis progresses include persistence of the interzonal mesenchyme at
the level of the proximal radioulnar joint space,
chondrification, and ossification. In one series of 37
patients (49 forearms) with congenital radioulnar
synostosis there were varying degrees of fusion within the synostosis, variable dysmorphisms of the radial head and, in one third of these patients, shortening
of the entire upper arm on the side affected (Yammine et al. 1998).
Radioulnar synostosis can occur as an isolated
anomaly, in association with other anomalies, or as
part of a more complex malformation spectrum.
When it occurs in isolation the defect is usually
sporadic, is slightly more frequent in males than in
females, and is bilateral in about 50% of cases (Reed
1992). Familial cases, with the condition inherited
as an autosomal dominant trait (OMIM 179300),
have also been documented (Davenport et al. 1924;
Hansen and Andersen 1970). In two families with
autosomal dominant radioulnar synostosis the skeletal defect occurred in association with amegakaryocytic thrombocytopenia (OMIM 605432). A mutation in the HOXA11 gene, mapping to 7p15, was
found to be responsible for the phenotype (Thompson and Nguyen 2000). Radioulnar synostosis also
sometimes occurs in association with other congenital defects, including clubfoot, hip dysplasia, Made-
lung deformity, thumb deficiency, carpal fusion, and
symphalangism of the ipsilateral hand (Kelikian
1974). Unilateral radioulnar synostosis of type 2 has
been described in association with generalized hypotonia, dolichocephaly with macrocephaly, developmental retardation, and a characteristic facial appearance with long narrow face and prominent nose
(OMIM 266255) (Der Kaloustian et al. 1992). The
constellation of findings such as radioulnar synostosis, radial ray abnormalities, and severe malformations in the male, including anencephaly, unilateral
renal agenesis, and a common dorsal mesentery
(OMIM 300233), may possibly be inherited as an Xlinked dominant trait (Manouvrier et al. 2000). Radioulnar synostosis has also been described in nonrandom association with short stature, microcephaly,
scoliosis, and mental retardation (Tsukahara syndrome, OMIM 603438) (Tsukahara et al. 1995).
Radioulnar synostosis is relatively common in the
Ehlers-Danlos syndromes (OMIM 130000, 130010,
130020, 130050, 130060, 130070, 130080, 130090,
225400, 225410) and occurs as a nonspecific finding together with other congenital anomalies, such
as arachnodactyly, clubfoot, flatfoot, triphalangeal
thumbs, carpo-tarsal fusions, supernumerary teeth,
micrognathia, delayed cranial ossification with large
fontanels, and elongation of the ulnar styloid process
(Beighton and Thomas 1969). Multiple calcified nodules in the subcutaneous tissue, measuring 2–8 mm
310
Chapter 5 · Long Bones
in diameter and closely resembling phleboliths, are
characteristic of these disorders and involve primarily the forearms. Additional findings relating to the
elbow in Ehlers-Danlos syndromes include olecranon bursitis and radial head dislocation. Radioulnar
synostosis is also a nonspecific finding in syndromes
with X-chromosome polyploidy, including XXXY and
XXXXY male phenotype, together with metacarpal
shortening, clinodactyly, accessory epiphyses, pointed phalangeal tufts, and retarded bone age (Ohsawa
et al. 1971). Bilateral radioulnar synostosis, with or
without subluxation of the radial heads, is common
in multiple synostoses syndrome (facio-audio-symphalangism syndrome, OMIM 186500), together with
multiple progressive joint fusions commencing in
the hand (Maroteaux et al. 1972). Proximal radioulnar synostosis is also part of the skeletal manifestations of mesomelic dysplasia, Nievergelt type (OMIM
163400), a condition with severe mesomelic shortlimbed dwarfism and typical rhomboid appearance
of the tibia and fibula, elbow dysplasia with radial
head dislocation, and fusions of the carpal and tarsal
bones. In Caffey disease (OMIM 114000), radioulnar
synostosis can occur as a late sequela of the deposition of new bone in the soft tissues adjacent to the
bone and subsequent fusion with the parent bone
(Claesson 1976).
Acquired radioulnar fusion may be a response
to trauma or infection, when it results from bone
proliferation and ossification of the interosseous ligament.
Radiographic Synopsis
AP, lateral and oblique projections. If the fusion is
fibrous, or ossification of the cartilaginous bridge
has not yet taken place, radiograms are not informative.
1. Proximal or ‘distal’ synostosis; radial head subluxation; ipsilateral upper limb shortening (isolated
radioulnar synostosis)
2. Radioulnar synostosis; calcified nodules in the
soft tissues of the forearm; radial head dislocation;
joint laxity (Ehlers-Danlos syndromes)
3. Proximal interphalangeal joint fusion; radioulnar
and radiohumeral fusion; progressive fusion of
carpals, tarsals, and other joints (multiple synostosis syndrome)
4. Proximal radioulnar synostosis; radial head dislocation; carpal and tarsal fusions; severe mesomelic limb shortening (mesomelic dysplasia, Nievergelt type)
Associations
• Acrocephalosyndactyly, Pfeiffer type
• Caffey disease
• Chromosome 18 trisomy syndrome
• Chromosome XXXXX syndrome
• Chromosome XXXXY syndrome
• Chromosome XXXY syndrome
• Cloverleaf skull syndrome
• Ehlers-Danlos syndromes
• Exostosis of the distal forearm
• Facio-auriculo-radial dysplasia
• Femorofacial syndrome
• Fetal alcohol syndrome
• Holt-Oram syndrome
• IVIC syndrome
• Lacrimo-auriculo-dento-digital syndrome
• Levy-Hollister syndrome
• Mesomelic dysplasia, Nievergelt type
• Multiple synostosis syndrome
• Nager syndrome
• Oculo-palato-skeletal syndrome
• Radioulnar synostosis–amegakaryocytic
thrombocytopenia
• Radioulnar synostosis, isolated
• Radioulnar synostosis–radial ray abnormalities–
severe malformations in males
• Radioulnar synostosis–short stature-microcephaly–scoliosis–mental retardation
• Radioulnar synostosis (unilateral)–developmental retardation–hypotonia
• Thalidomide-induced embryopathy
• Thanatophoric dysplasia
• Trauma
References
Bauer M, Jonsson K. Congenital radioulnar synostosis. Scand J
Plast Reconstr Surg 1988; 22: 251–5
Beighton P, Thomas ML. The radiology of the Ehlers-Danlos
syndrome. Clin Radiol 1969; 20: 354–61
Claesson I. Infantile cortical hyperostosis. Report of a case
with late manifestation. Acta Radiol Diagn 1976; 17: 594–
600
Cleary JE, Omer GE. Congenital proximal radio-ulnar synostosis. J Bone Joint Surg Am 1985; 67: 539–45
Davenport CB, Taylor HL, Nelson LA. Radio-ulnar synostosis.
Arch Surg 1924; 8: 705–62
Der Kaloustian VM, McIntosh N, Silver K, Blaichman S, Halal F.
Unilateral radio-ulnar synostosis, generalized hypotonia,
developmental retardation, and a characteristic facial appearance in sibs: a new syndrome. Am J Med Genet 1992;
43: 942–5
Hansen OH, Andersen NO. Congenital radio-ulnar synostosis:
report of 37 cases. Acta Orthop Scand 1970; 41: 225–30
Abnormalities of the Long Bones in the Upper Extremities
Kelikian H. Congenital deformities of the hand and forearm.
W. B. Saunders Company, Philadelphia, 1974, pp 939–74
Manouvrier S, Moerman A, Coeslier A, Devisme L, Boute O, Le
Merrer M. Radioulnar synostosis, radial ray abnormalities,
and severe malformations in the male: a new X-linked
dominant multiple congenital anomalies syndrome? Am J
Med Genet 2000; 90: 351–5
Maroteaux P, Bouvet JP, Briard ML. La maladie des synostoses
multiples. Nouv Presse Med 1972; 1: 3041–7
Mital MA. Congenital radioulnar synostosis and congenital
dislocation of the radial head. Orthop Clin North Am 1976;
7: 375–83
Ohsawa T, Furuse M, Kikuchi Y, Suda Y, Tamiya T. Roentgenographic manifestations of Klinefelter’s syndrome. Am J
Roentgenol Radium Ther Nucl Med 1971; 112: 178–84
Reed MH. Pediatric skeletal radiology. Williams & Wilkins,
Baltimore, 1992, p. 376
Thompson AA, Nguyen LT. Amegakaryocytic thrombocytopenia and radio-ulnar synostosis are associated with
HOXA11 mutation. Nat Genet 2000; 26: 397–8
Tsukahara M, Matsuo K, Furukawa S. Radio-ulnar synostosis,
short stature, microcephaly, scoliosis, and mental retardation. Am J Med Genet 1995; 58: 159–60
Yammine K, Salon A, Pouliquen JC. Congenital radioulnar synostosis. Study of a series of 37 children and adolescents.
Chir Main 1998; 17: 300–8
Humeroradial and Humeroulnar Synostosis
䉴 [Fusion between humerus and radius
and humerus and ulna, respectively]
Both these anomalies are less common than radioulnar synostosis. Congenital, isolated humeroulnar
synostosis is exceedingly rare. Acquired cases of
humeroulnar fusion taking the form of bony bridging between contiguous foci of heterotopic calcification are well known (Hastings and Graham 1994).
From a clinical standpoint, both humeroradial and
humeroulnar synostosis imply fixed flexion of the
forearm, usually near 90° (Fig. 5.28).
Both sporadic and genetic cases of humeroradial
synostosis are encountered. The genetic forms are
characterized by bilateral involvement and lack of
the distal ulnar malformations (longitudinal deficiency of ulna) that are common in the sporadic cases (Hunter et al. 1976). Fusion of all three bones articulating at the elbow joint can also occur sporadically,
in association with upper limb oligo-ectro-syndactyly (Hersh et al. 1989). Three entities of humeroradial
synostosis can be delineated: (a) autosomal dominant ankylosis of the elbow as part of a systemic
disorder causing multiple synostoses with brachymesophalangism (facio-audio-symphalangism syndrome); (b) autosomal recessive humeroradial synostosis (OMIM 236400) with dysgenesis of the ulna
311
but without oligodactyly as part of a syndromal disorder; (c) autosomal recessive humeroradial synostosis with great variability within families (nongerminal, uni- or bilateral) as part of the ulnar malformation and oligodactyly (SC phocomelia syndrome).
Consanguinity is frequent in the families of patients
who have inherited this condition as a recessive trait
(Keutel et al. 1970).
In multiple synostoses syndrome (facio-audiosymphalangism syndrome, OMIM 186500), a disorder with an autosomal dominant mode of inheritance and with variable expression, multiple progressive joint fusions with onset in early childhood at the
proximal interphalangeal joints (proximal symphalangism) and progression to the carpal, tibio-tarsal,
and tarsal articulations are typically encountered.
Ankylosis of other joints, including the middle-ear
ossicles (otosclerotic deafness), cervical vertebrae,
hips, and radiohumeral joints, develops with age (da
Silva et al. 1984; Herrman 1974). Affected patients
show a broad, tubular (hemicylindrical) nose without alar flare (Maroteaux et al. 1972). Linkage to
17q21-q22 has been demonstrated (Krakow et al.
1998). The detection of mutations in the Noggin gene
both in familial autosomal dominant multiple synostoses syndrome and in families with proximal symphalangism indicates that these are allelic disorders
(Gong et al. 1999). Roberts-SC phocomelia syndrome
(OMIM 268300) manifests with limb reduction defects (absent, hypoplastic, bowed, and deformed long
and short tubular bones, missing rays), fused thin
ribs with abnormal rib number, and platyspondyly
with reduced intervertebral spaces. Camptodactyly
and clinodactyly are occasional features (Herrmann
et al. 1969). The phenotype of what originally was
considered to be a separate entity, SC phocomelia, is
milder, with longer survival (Hunter et al. 1976; Pfeiffer and Braun-Quentin 1994). Humeroradial synostosis can also occur in association with an unusual type
of multiple synostosis syndrome (humeroradial synostosis/multiple synostosis syndrome, OMIM 236410)
that involves carpal, tarsal, and phalangeal joints, with
apparent agenesis of the distal phalanges of the
postaxial digits (Richieri-Costa et al. 1986). Additional findings in this constellation include plagiobrachycephaly, prominent forehead, broad nasal root, small
ears with hypoplastic lobes, and normal mental development. Based on parental consanguinity, autosomal recessive inheritance has been suggested. Bilateral humeroradial synostosis, with fixed flexion of
the elbow, is constant in Antley-Bixler syndrome
(trapezoidocephaly/synostosis, OMIM 207410), which
is probably an autosomal recessive disorder. The
312
Chapter 5 · Long Bones
Fig. 5.28. Humeroradial synostosis in a woman patient.
There is humeroradial synostosis with 90° fixed-flexion deformity of the elbow. The long
bones of the forearm are short
and undermodeled. There is
triquetro-pisiform fusion in
the carpus, and brachymesophalangy of the 2nd and 5th
fingers, with clinodactyly of
the 5th. No signs of symphalangism are detected. The patient is short in stature and has
bowed tibias and normal auditory function
syndrome also displays craniosynostosis with brachycephaly and frontal bossing, midface hypoplasia,
choanal atresia, depressed nasal bridge, dysplastic
ears, stenotic external auditory canals, bowed femurs,
joint contractures, narrow chest with gracile ribs,
arachnodactyly, clubfoot, carpo-tarsal synostosis,
and long bone fractures (Antley and Bixler 1975).
Humeroradial synostosis, together with brachycephaly, mild syndactyly, and broad thumbs and toes,
also occurs with Pfeiffer syndrome (acrocephalosyndactyly, OMIM 101600) (Martsolf et al. 1971). Humeroradio-ulnar synostosis has been noted in association
with distal humeral bifurcation and tridactylous
ectrosyndactyly (Gollop and Coates 1983; Leroy and
Speeckaert 1984).
Radiographic Synopsis
AP and lateral projections
1. Humeroradial and radioulnar synostosis; proximal symphalangism; ankylosis of other joints
(multiple synostoses syndrome)
2. Humeroradial synostosis; ulnar dysgenesis (autosomal recessive form)
3. Humeroradial synostosis; ulnar malformation;
oligodactyly (SC phocomelia syndrome)
4. Humeroradial synostosis; bowed femurs; joint
contractures; carpo-tarsal synostosis; femoral
fractures (Antley Bixler syndrome)
Associations
• Acrocephalosyndactyly, Pfeiffer type
• Antley-Bixler syndrome
• Cloverleaf skull
• Familial humeroradial synostosis
• Femur-fibula-ulna syndrome
• Holt-Oram syndrome
• Humeroradial synostosis/multiple synostosis syndrome
• Multiple synostoses syndrome (facio-audio-symphalangism syndrome)
• Roberts-SC phocomelia syndrome
References
Antley RM, Bixler D. Trapezoidocephaly: midfacial hypoplasia
and cartilage abnormalities with multiple synostoses and
skeletal fractures in Amsterdam. Birth Defects Orig Art Ser
1975; 2: 397–401
Da-Silva EO, Filho SM, de Albuquerque SC. Multiple synostosis
syndrome: study of a large Brazilian kindred. Am J Med
Genet 1984; 18: 237–47
Gollop TR, Coates V. Apparent bifurcation of distal humerus
with oligoectro-syndactyly. Am J Med Genet 1983; 14:
591–3
Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, BabulHirji R, Hudgins L, Cremers CW, Cremers FPM, Brunner
HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML. Heterozygous mutations in the gene encoding noggin affect human
joint morphogenesis. Nat Genet 1999; 21: 302–4
Hastings H, Graham TJ. The classification and treatment of
heterotopic ossification about the elbow and forearm.
Hand Clin 1994; 10: 417–37
Herrmann J. Symphalangism and brachydactyly syndrome:
report of the WL symphalangism-brachydactyly syndrome: review of literature and classification. Birth Defects
Orig Art Ser 1974; 5: 23–53
Herrmann J, Feingold M, Tuffli GA, Opitz JM. A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: the
“pseudothalidomide” or “SC-syndrome”. Birth Defects
Orig Art Ser 1969; 3: 81–9
Hersh JH, Joyce MR, Profumo LE. Humero-radio-ulnar synostosis: a new case and review. Am J Med Genet 1989; 33:
170–1
Hunter AGW, Cox DW, Rudd NL. The genetics of and associated clinical findings in humero-radial synostosis. Clin Genet
1976; 9: 470–8
Keutel J, Kindermann I, Mockel H. Eine wahrscheinlich autosomal recessiv vererbte Skeletmissbildung mit Humeroradialsynostose. Humangenetik 1970; 9: 43–53
Abnormalities of the Long Bones in the Upper Extremities
Krakow D, Reinker K, Powell B, Cantor R, Priore MA, Garber A,
Lachman RS, Rimoin DL, Cohn DH. Localization of a multiple synostoses-syndrome disease gene to chromosome
17q21–22. Am J Hum Genet 1998; 63: 120–4
Leroy JG, Speeckaert MTC. Humeroradioulnar synostosis appearing as distal humeral bifurcation in a patient with distal phocomelia of the upper limbs and radial ectrodactyly.
Am J Med Genet 1984; 18: 365–8
Maroteaux P, Bouvet JP, Briard ML. La maladie des synostoses
multiples. Nouv Presse Med 1972; 1: 3041–7
Martsolf JT, Cracco JB, Carpenter GG, O’Hara AE. Pfeiffer syndrome. An unusual type of acrocephalosyndactyly with
broad thumbs and great toes. Am J Dis Child 1971; 121:
257–62
Pfeiffer RA, Braun-Quentin C. Genetic nosology and counseling of humeroradial synostosis. Genet Couns 1994; 5:
269–74
Richieri-Costa A, Pagnan NAB, Ferrareto I, Masiero D. Humeroradial/multiple synostosis syndrome in a Brazilian child
with consanguineous parents: a new multiple synostosis
syndrome? Rev Brasil Genet 1986; 9: 115–22
Madelung Deformity
䉴 [Short and dorsolaterally curved radius, tilting
of distal ulna, and dorsal subluxation/dislocation
of ulna]
The primary event in Madelung deformity is a
growth disturbance that involves the radius while
sparing the ulna (Anton et al. 1938). The unequal
growth of radius and ulna results in dorsal bowing of
distal radius, sloping of its distal epiphysis, and
wedging of the carpus (triangularization of the carpus) between deformed radius and protruding ulna,
with the lunate at the apex of the wedge. As a consequence, a decreased carpal angle is part of the radiographic spectrum of the deformity. The radius is
short, dorsolaterally curved, with a triangular distal
epiphysis owing to premature fusion of its medial
portion. Although the ulna is grossly normal, reducible dorsal subluxation of the distal ulnar end is a
feature (Reed 1992).
Madelung deformity is a constant and prominent
feature in dyschondrosteosis (Léri-Weill disease,
OMIM 127300), an X-linked dominant disorder manifesting in late childhood with more severe expression in girls (Herdman et al. 1966). Madelung
deformity and dyschondrosteosis are phenotypic expressions of the same genetic defect. The clinical
spectrum ranges from Madelung deformity alone in
mild cases to varying degrees of short stature of the
mesomelic type in addition to the Madelung deformity in the more severe manifestations. Lower leg
shortening, involving especially the tibia and fibula,
313
with prominence of the medial portion of the tibia,
are characteristic features. Short hands and feet,
short 4th metacarpal, tibial bowing, genu valgum,
and coxa valga may be additional manifestations. Patients with dyschondrosteosis are heterozygous for
the SHOX gene (OMIM 602504), whose homozygosity causes mesomelic dysplasia, Langer type (OMIM
249700) (Belin et al. 1998).When the deformity is isolated, clinical complaints include variable degrees of
joint motion limitation at the wrist or elbow or both.
Occasionally, joint pain is reported. Symptomatology
may subside over time (Henry and Thorburn 1967).
In patients with hereditary multiple exostoses (OMIM
133700), a deformity of the forearm resembling
Madelung deformity is sometimes found as a secondary effect of exostosis development. Most frequently, the distal end of the ulna is involved, resulting in disproportionate ulnar shortening and tapering and lateral bowing of radius with medial sloping
of its articular surface (Hennekam 1991). Multiple
cartilaginous excrescences in the tubular and flat
bones are cardinal features. A Madelung-like deformity and cubitus valgus are frequent manifestations
of Turner syndrome (chromosome X monosomy syndrome).
Forearm deformities resembling Madelung deformity in type can also occur as secondary effects,
usually after trauma causing injury to the radial epiphysis (Lamb 1988).
Radiographic Synopsis
AP and lateral projections
1. Short radius; dorsolateral bowing of radius; triangularization of distal radial epiphysis; ulnar
and palmar slant of the radial articular surface;
dorsal subluxation of distal ulna; triangular configuration of the carpus, with the lunate at the
apex of the triangle; decreased carpal angle
(Madelung deformity, dyschondrosteosis, Turner
syndrome)
2. Short ulna; variable deformation of distal ulna by
exostoses; bowing of radius; displacement of the
distal end of radius toward ulna (hereditary multiple exostoses)
Associations
• Dyschondrosteosis (Leri-Weill syndrome)
• Enchondromatosis
(Ollier disease, Maffucci syndrome)
• Hereditary multiple exostoses
• LEOPARD syndrome
• Turner syndrome
314
Chapter 5 · Long Bones
References
Anton JI, Reitz GB, Spiegel MB. Madelung’s deformity. Ann
Surg 1938; 108: 411–39
Belin V, Cusin V, Viot G, Girlich D, Toutain A, Moncla A, Vekemans M, Le Merrer M, Munnich A, Cormier-Daire V. SHOX
mutations in dyschondrosteosis (Leri-Weill syndrome).
Nat Genet 1998; 19: 67–9
Hennekam RCM. Hereditary multiple exostoses. J Med Genet
1991; 28: 262–6
Henry A, Thorburn MJ. Madelung’s deformity. A clinical and
cytogenetic study. J Bone Joint Surg Br 1967; 49: 66–73
Herdman RC, Langer LO Jr, Good RA. Dyschondrosteosis, the
most common cause of Madelung’s deformity. J Pediatr
1966; 68: 432–41
Lamb D. Madelung deformity. J Hand Surg (Br) 1988; 13: 3–4
Reed MH. Pediatric skeletal radiology. Williams & Wilkins,
Baltimore, 1992, p. 376
Abnormalities of the Long Bones
in the Lower Extremities
Current terminology and classification systems for
limb defects have been summarized in the previous
section.
In addition to the deformities resulting from failure of formation of parts, common defects of limb
alignment, notably genu varum and genu valgum, are
included in this section, as are patellar defects. The
mechanisms involved in the development of lower
limb malalignment can be extremely difficult to
understand, given the complex interaction between
bone structure, dynamics of bony growth, and the
mechanical forces applied through the knee. For example, a depressed medial tibial plateau might be due
to weakening of the bone, decreased growth rate at
the medial portion of the tibial epiphysis, or excessive mechanical stress on the medial side of the
knee. Similarly, it is impossible to establish reliably
whether the medial tibial plateau is underdeveloped
or the medial femoral condyle is abnormally prominent in cases in which the two defects coexist (e.g., in
the nail-patella syndrome). These mechanisms are
briefly mentioned below when appropriate.
Genu Varum
䉴 [Increased distance between the knees
with the legs fully extended, bowleg]
Genu varum is relatively common in children. Bowleg deformity occurring in otherwise normal infants
and young children is transitory in most cases,
representing a physiological developmental varia-
Fig. 5.29. Blount disease in a 6-year-old black girl. Note sharp
inferior bending of the medial portion of the tibial metaphysis, sloping of the tibial epiphysis, and irregular calcification
on the medial tibial margin (stage III according to the Catonné
classification)
tion. Physiological genu varum changes to valgus at
18–36 months of age and subsequently resolves
spontaneously by the age of 6–7 years (Silverman
1990; Hansson and Zayer 1975). When the varus deformity persists beyond this age the increased vertical stress applied along the medial compartment of
the knee can lead to impaction and beaking of the
tibial metaphysis, resulting in progressive tibial
growth impairment (Swischuk and John 1995).
Blount disease (idiopathic or infantile tibia vara,
OMIM 259200), the most common focal disorder
producing progressive varus deformity of the knee in
young children (Blount 1937), is regarded as the irreversible stage of physiological genu varum (Brooks
and Gross 1995). However, there is no consensus
about whether Blount disease is caused by an intrinsic disturbance in endochondral ossification or by
increased mechanical compression applied to the
medial portion of the tibial growth plate. Blount disease is found predominantly in obese children with
an early onset of walking (Do 2001). Additional predisposing factors include intense physical activity
Abnormalities of the Long Bones in the Lower Extremities
and rapid growth (Wenger et al. 1984). The occurrence of Blount disease in a father and osteochondritis dissecans of the knees in his two sons suggests a
pathogenetic link between the two (Tobin 1957).
Blount disease is usually bilateral, but not symmetrical. Mild cases revert to normal by the age of
3–4 years, while severe cases may require tibial osteotomy. Effective treatment can prevent permanent
intra-articular incongruity (Johnston 1990). Tibia
vara can also occur later in life (Blount disease, adolescent type) in adolescents, who are often overweight (Thompson and Carter 1990). This less common type of tibia vara is more common in blacks
than whites and in males than females, is usually unilateral, and has been related to a segmental defect of
the growth plate function, i.e., partial or complete
closure of the medial portion of the tibial physis by
bone bridges (Fig. 5.29). Widening of the lateral segment of the epiphyseal growth plate may coexist
(Currarino and Kirks 1977). Knee pain is the primary
presenting clinical symptom. In male patients who
undergo surgical correction the rate of recurrence
approaches 50% (Arai et al. 2001; Thompson et al.
1984).
Genu varum can be found in association with a
number of additional disease processes, either focal
or systemic. Focal factors include bone infections,
traumatic physeal injuries, and benign neoplasms.
Asymmetrical loss of the articular cartilage of the
knee, with involvement of the medial compartment
and relative preservation of the lateral compartment,
can also result in unilateral or bilateral genu varum
(Garcia-Gonzales and Resnick 1992). Severe osteoarthritis and calcium pyrophosphate dihydrate crystal
deposition disease (OMIM 118600) are striking examples. Genu varum may also accompany metabolic
disorders, such as vitamin D-resistant rickets, renal
osteodystrophy, and hypophosphatasia, and skeletal
dysplasias, such as campomelic dysplasia, achondroplasia, and metaphyseal chondrodysplasia. In
some of these disorders the joint deformity is caused
by the inherent bone defect. In others, the primary
defect responsible for the altered biomechanics
about the knee and, in turn, for the development of
genu varum is a genetically determined collagen or
matrix protein abnormality of the articular cartilage
or the deposition of pathologic products (mucopolysaccharides in mucopolysaccharidoses, polymerized
homogentisic acid in alkaptonuria) in the cartilage.
In still other situations the joint deformation is mediated by the development of premature osteoarthritis (Balint and Szebenyi 2000). There are several potential locations within the lower extremity for the
315
disease process that causes genu varum. The proximal tibia is the one most commonly implicated. Lateral bowing of the distal segment of the femur occasionally plays a part. The association of genu varum
with various proximal femoral physeal conditions,
including slipped capital femoral epiphysis, has long
been recognized (Lovejoy and Lovell 1970). There are
factors in the joints, and probably in the ligaments,
that are responsible for some of the bowing. Epiphyseal deformities, regardless of their origin, are frequently the ‘prime movers’ in genu varum. Depending on whether epiphyseal diminution occurs in the
medial or in the lateral portion of the epiphysis, genu
varum or genu valgum, respectively, will result.
Radiographic Synopsis
AP projections in the upright weight-bearing position.
Serial observations are often necessary to determine
whether the deformity is progressing and likely to
develop into Blount disease, or is resolving. The
tibiofemoral angle and tibial metaphyseal-diaphyseal
angle are commonly measured, but both are subject
to measurement error (Henderson et al. 1990). The
tibiofemoral angle is the angle between lines drawn
along the longitudinal axes of the tibia and femur
(normal range: 6–34° at age 11–20 months; and 0–35
at age 21–30 months). The tibial metaphyseal–diaphyseal angle is the angle between a line parallel to
the tibial plateau and one drawn perpendicular to the
long axis of the tibia (normal range: –0.5 to 11° at age
11–20 months and –2.5 to 10° at age 21–30 months)
(Levine and Drennan 1982). Both angles are widened
in tibia vara. The intercondylar or intermalleolar distance is also commonly measured (Arazi et al. 2001).
1. Lateral and dorsal bowing of the tibial shaft with
medial and dorsal beaking of the tibia and femur
at the metaphysis; thickening of the medial and
dorsal cortical walls of tibia (physiologic bowleg)
2. Sharp bending of the medial segment of the tibial
metaphysis caudad and mediad; sloping of the
medial end of the tibial epiphysis; compensatory
hypertrophy of the medial femoral condyle; tibial
spur projecting medially and dorsally (Blount disease)
Associations
• Achondroplasia
• Blount disease
• Calcium pyrophosphate dihydrate crystal deposition disease
• Campomelic dysplasia
• Dyggve-Melchior-Clausen disease
• Dysplasia epiphysealis hemimelica
316
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Chapter 5 · Long Bones
Fibrocartilaginous dysplasia, focal
Infection
Marshall-Smith syndrome
Metaphyseal chondrodysplasia, McKusick type
Metaphyseal chondrodysplasia, Schmid type
Osteoarthritis, all types
Osteogenesis imperfecta
Physiological bowleg
Pseudoachondroplasia
Radiation
Rickets, all types
Spondyloepimetaphyseal dysplasia
Thrombocytopenia-absent radius syndrome
Trauma
Turner syndrome
Swischuk LE, John SD. Differential diagnosis in pediatric radiology. Williams & Wilkins, Baltimore, 1995, p. 207
Thompson GH, Carter JR, Smith CW. Late-onset tibia vara: a
comparative analysis. J Pediatr Orthop 1984; 4: 185–94
Thompson GH, Carter JR. Late-onset tibia vara (Blount’s disease): current concepts. Clin Orthop 1990; 255: 24–35
Tobin WJ. Familial osteochondritis dissecans with associated
tibia vara. J Bone Joint Surg Am 1957; 39: 1091–105
Wenger DR, Mickelson M, Maynard JA. The evolution and
histopathology of adolescent tibia vara. J Pediatr Orthop
1984; 4: 78–88
Genu Valgum
䉴 [Decreased distance between the knees
with a wide gap separating the ankles
when legs are fully extended]
References
Arai K, Haga N, Taniguchi K, Nakamura K. Magnetic resonance
imaging findings and treatment outcome in late-onset tibia
vara. J Pediatr Orthop 2001; 21: 808–11
Arazi M, Ogun TC, Memik R. Normal development of the
tibiofemoral angle in children: a clinical study of 590 normal subjects from 3 to 17 years of age. J Pediatr Orthop
2001; 21: 264–7
Balint G, Szebenyi B. Hereditary disorders mimicking and/or
causing premature osteoarthritis. Baillieres Best Pract Res
Clin Rheumatol 2000; 14: 219–50
Blount WP. Tibia vara: osteochondrosis deformans tibiae.
J Bone Joint Surg Am 1937; 19: 1–29
Brooks WC, Gross RH. Genu Varum in children: diagnosis and
treatment. J Am Acad Orthop Surg 1995; 3: 326–35
Currarino G, Kirks DR. Lateral widening of epiphyseal plates
in knees of children with bowed legs. AJR Am J Roentgenol
1977; 129: 309–12
Do TT. Clinical and radiographic evaluation of bowlegs. Curr
Opin Pediatr 2001; 13: 42–6
Garcia-Gonzalez A, Resnick D. Is depression of the medial tibial plateau more frequent in pyrophosphate arthropathy
than in osteoarthritis? J Rheumatol 1992; 19: 182–3
Hansson LI, Zayer M. Physiological genu varum. Acta Orthop
Scand 1975; 46: 221–9
Henderson RC, Lechner CT, DeMasi RA, Greene WB Variability in radiographic measurement of bowleg deformity in
children. J Pediatr Orthop 1990; 10: 491–4
Johnston CE. Infantile tibia vara. Clin Orthop 1990; 255: 13–23
Levine AM, Drennan JC. Physiological bowing and tibia vara.
The metaphyseal-diaphyseal angle in the measurement of
bowleg deformities. J Bone Joint Surg Am 1982; 64: 1158–63
Lovejoy JF Jr, Lovell WW. Adolescent tibia vara associated with
slipped capital femoral epiphysis. A report of two cases.
J Bone Joint Surg Am 1970; 52: 361–4
Silverman FN. Osteochondroses and miscellaneous alignment
disorders. In: Silverman FN, Kuhn JP (eds.) Caffey’s pediatric X-ray diagnosis. Year Book Medical Publisher, Inc.,
Chicago, 1990, pp. 1821–42
In normal children, genu valgum – also termed
knock-knee – represents the recovery phase from
physiological bowleg and usually resolves by
6–7 years of age. Genu valgum persisting beyond that
age is abnormal. There are several mechanisms involved in its development. Weakening of the muscles
inserted at the knees and joint laxity certainly play a
part. Articular joint diseases with preferential involvement of the lateral femorotibial articulation may
be implicated. Congenital deficiency of the lateral
portion of the distal femur or proximal tibia is another potential mechanism. Genu valgum occurring as a
compensatory mechanism of ipsilateral progressive
coxa vara has also been described (Shim et al. 1997).
Genu valgum is one symptom of a number of distinct disorders in which hypotonia and muscular
weakness or ligamentous and capsular laxity are the
cardinal manifestations (Swischuk and John 1995).
For example, in homocystinuria (OMIM 236200), genu
valgum and patella alta are manifestations of joint laxity. In this disorder, abnormal joint laxity at some
joints typically occurs in conjunction with flexion
contractures at other joints (Brenton et al. 1972). Multiple growth recovery lines, elongation of the limbs,
and osteoporosis are additional features. Two distinct
processes can lead to knee malalignment in osteogenesis imperfecta (OMIM 166200): fracture deformities,
resulting in distortion of the articular surfaces and
joint incongruity; and ligamentous and capsular laxity. Bowing of the long bones, especially of the tibias,
can be associated with genu valgum in neurofibromatosis type 1 (OMIM 162220). Skeletal changes in
this condition include pathologic fractures with
defective healing and pseudarthrosis. In turn, failure
of fracture healing may cause growth inhibition at
Abnormalities of the Long Bones in the Lower Extremities
317
Fig. 5.30 a, b. Spondylometaphyseal dysplasia, Algerian
type, in an 8-year-old boy.
There is strikingly short stature (boy’s height is 85 cm.,
the 3rd normal percentile
being 115 cm), limb shortening (most prominent in
the humeri), genu valgum,
severe metaphyseal alterations (irregularities, fragmentation, sclerosis), grossly unremarkable epiphyses, and coxa
vara. (From Kozlowski et al.
1988)
a
the tibial physis, thereby resulting in genu valgum.
Angular deformities of joints other than the knee are
also possible (Gregg et al. 1982). A high incidence of
genu valgum has been reported in patients with fluorosis, a condition caused by chronic intoxication
with fluorine. As already mentioned, the main radiographic abnormalities in this disorder include diffuse osteosclerosis, periostitis, ligamentous calcifications, vertebral osteophytosis, and hypoplasia and
irregularity of the teeth (Resnick 1995). Whether
genu valgum is secondary to muscular weakening, a
neurological complication of fluorosis, or to changes
in the mechanical properties of the bones, is not
known. Genu valgum is also described among the
side-effects of deferoxamine, an iron-chelating agent
used in patients with systemic hemochromatosis.
The toxic effects of this drug to the skeleton are most
prominent in the metaphyses of the tubular bones,
particularly at the knee and wrist, and consist of
metaphyseal widening, cupping, fraying, and cystic
changes of the subchondral bone. In these cases genu
valgum represents a mechanical adjustment to the
primary metaphyseal lesions (de Virgiliis et al. 1988).
Intrinsic disturbances of epiphyseal growth rate such
as are encountered in multiple epiphyseal dysplasia
(OMIM 132400) can result in either genu varum or
genu valgum deformity, depending on whether the
growth deficiency, and the resultant epiphyseal abnormalities, are predominant at the medial or at the
lateral side of the knee, respectively. In addition to
b
being flattened, the epiphyses are variably delayed in
appearance, irregular, and fragmented. Short hands
and feet, joint stiffness and pain, and limping are
additional manifestations (Hunt et al. 1967). A distinct disorder of limb malalignment, termed St. Helena familial genu valgum (OMIM 137370) because of
the geographical localization and anatomical distribution of the abnormalities, has been described by
Beighton et al. (1986). In this disorder of autosomal
dominant inheritance, malalignment is most prominent at the knees, but is also evident at the elbows
and wrists. Severe genu valgum is due primarily to
hypoplasia of the lateral femoral condyles and is further exacerbated by progressive degenerative osteoarthropathy. Another condition in which genu valgum deformity is a cardinal feature is spondylometaphyseal dysplasia, Algerian type (OMIM 184253). The
clinical and radiographic manifestations of the disease include severe dwarfism, genu valgum, myopia,
progressive kyphoscoliosis, wrist deformities, and
severe metaphyseal dysplasia of the long tubular
bones (Fig. 5.30a,b). The hands and feet are little affected. The metaphyseal changes in this disorder are
intermediate in severity between the mild alterations
of the common type of spondylometaphyseal dysplasia, Kozlowski type (OMIM 184252) and the severe
changes seen in metaphyseal dysplasia, Jansen type
(OMIM 156400). The delayed bone age in Kozlowski
spondylometaphyseal dysplasia and the severe involvement of the hands in Jansen metaphyseal dys-
318
Chapter 5 · Long Bones
plasia are additional features distinguishing these
from the Algerian type of spondylometaphyseal dysplasia (Kozlowski et al. 1988).
Genu valgum and degenerative osteoarthritis of
the knee are closely intertwined. Osteoarthritic narrowing of the articular space on the lateral side of the
knee leads to genu valgum deformity. On the other
hand, in the presence of genu valgum, the weightbearing forces pass through the lateral compartment
of the knee, thus predisposing to osteoarthritis. In
rheumatoid arthritis, osseous changes about the knee
characteristically involve both the medial and the lateral femorotibial compartments. However, there are
cases in which the lateral femorotibial compartment
is affected more severely than the medial, thus resulting in valgus deformity of the knee.
Radiographic Synopsis
AP projections in the upright weight-bearing position.
The tibiofemoral angle and tibial metaphyseal-diaphyseal angle are narrower than the normal range.
The intercondylar distance is decreased and the intermalleolar distance is increased. For the above
measurements see the previous section.
1. Genu valgum; patella alta; multiple growth recovery lines; limb elongation; osteoporosis (homocystinuria)
2. Genu valgum; fracture deformities; pseudarthrosis (neurofibromatosis type 1)
3. Genu valgum; periostitis (fluorosis)
4. Genu valgum; metaphyseal abnormalities; subchondral cysts (deferoxamine)
5. Genu valgum or genu varum; epiphyseal abnormalities (multiple epiphyseal dysplasia)
6. Severe genu valgum; hypoplasia of the lateral
femoral condyles (St. Helena familial genu valgum)
Associations
• Achondroplasia
• Acro-cephalo-polysyndactyly, Carpenter type
• Bardet-Biedl syndrome
• Chondrodysplasia punctata
• Chondroectodermal dysplasia
• Cohen syndrome
• Diaphyseal dysplasia (Engelmann)
• Dyggve-Melchior-Clausen disease
• Dyschondrosteosis
• Dysplasia epiphysealis hemimelica
• Fluorosis
• Hajdu-Cheney syndrome
• Homocystinuria
• Hypophosphatasia
• Metaphyseal chondrodysplasia
•
•
•
•
•
•
•
•
•
•
•
•
Mucopolysaccharidoses
Multiple epiphyseal dysplasia
Nail-patella syndrome
Neurofibromatosis
Osteogenesis imperfecta
Parastremmatic dwarfism
Physiological knock knee
Pyle disease
Rickets
Spondyloepimetaphyseal dysplasia, Strudwick type
Spondyloepiphyseal dysplasia, Maroteaux type
Spondylometaphyseal dysplasia, Algerian type
References
Beighton P, Myers HS, Aldridge SJ, Sedgewick J, Eickhoff S. St.
Helena familial genu valgum. Clin Genet 1986; 30: 309–14
Brenton DP, Dow CJ, James JI, Hay RL, Wynne-Davies R.
Homocystinuria and Marfan’s syndrome. A comparison.
J Bone Joint Surg Br 1972; 54: 277–98
De Virgiliis S, Congia M, Frau F, Argiolu F, Diana G, Cucca F,
Varsi A, Sanna G, Podda G, Fodde M et al. Deferoxamine-induced growth retardation in patients with thalassemia major. J Pediatr 1988; 113: 661–9
Gregg PJ, Price BA, Ellis HA, Stevens J. Pseudarthrosis of the
radius associated with neurofibromatosis. A case report.
Clin Orthop 1982; 171: 175–9
Hunt DD, Ponseti IV, Pedrini-Mille A, Pedrini V. Multiple epiphyseal dysplasia in two siblings. Histological and biochemical analyses of epiphyseal plate cartilage in one.
J Bone Joint Surg Am 1967; 49: 1611–27
Kozlowski K, Bacha L, Massen R, Ayati M, Sator S, Brahimi L. A
new type of spondylo-metaphyseal dysplasia-Algerian
type. Report of five cases. Pediatr Radiol 1988; 18: 221–6
Resnick D. Disorders due to medications and other chemical
agents. In Resnick D: Diagnosis of bone and joint disorders.
W.B. Saunders Company, Philadelphia, 1995 (3rd ed.),
pp. 3309–42
Shim JS, Kim HT, Mubarak SJ, Wenger DR. Genu valgum in
children with coxa vara resulting from hip disease. J Pediatr
Orthop 1997; 17: 225–9
Swischuk LE, John SD. Differential diagnosis in pediatric radiology. Williams & Wilkins, Baltimore, 1995, p. 207
Proximal Femoral Focal Dysplasia
䉴 [Deficiency of the proximal femoral segment]
The term proximal focal femoral deficiency is applied to a spectrum of malformations in which aplasia of the proximal femur, deficiency of the iliofemoral articulation, and limb length discrepancy
occur in varying degrees (Bryant and Epps 1991)
(Fig. 5.31a–c). The defect can occur with or without
fibular hemimelia and can be unilateral or bilateral in
Abnormalities of the Long Bones in the Lower Extremities
a
319
b
Fig. 5.31 a, b. Proximal femoral focal dysplasia in a child. a Immediately after birth, the right femoral head is not ossified, and proximal
femoral shaft is bulbous. Classification was uncertain at this time.
b A later radiograph taken when the child was 4 years old shows an
ossified femoral head within the acetabulum. There is a large gap
between the femoral head and proximal femoral shaft because the
femoral neck is still unossified. c Postmortem radiograph of a newborn male with splenogonadal fusion and complex limb defects.
The right femur is short, proximally deficient, with aplastic femoral
head. The acetabulum is dysplastic/absent, and the femur articulates
proximally with the ilium. There is significant femoral length discrepancy. The left tibia and fibula, and the left fibula are absent. The
right tibia is hypoplastic. Most of the bones in the left foot are lacking. Note also left clubfoot. The upper limbs (not shown) were unaffected. [Reprinted from Hillmann et al. 1987 (a, b, with permission)
and Gouw et al. 1985 (c)]
presentation (Stormer 1997). Most commonly, the
defect is isolated and unilateral. When bilateral, the
defect is often asymmetrical in distribution, with
femoral aplasia on one side and femoral hypoplasia
on the other. The right side and the male sex are preferentially affected. Four classes of increasing severity
have been identified (Levinson et al. 1977; Lange et al.
1978; Goldman et al. 1978). Class A includes cases in
which the femur is short, the femoral head is present,
and the acetabulum is adequate. In class B, the femur
is short and dysplastic and there is a large unossified
gap between the femoral head and the distal segment. The acetabulum is adequate or mildly dysplastic. Class C proximal focal femoral deficiency con-
c
sists of femoral head aplasia, severe dysplasia of the
acetabulum, and shortness of the femur with proximal tapering. In class D, only a short, deformed distal
femoral segment is found, while both the femoral
head and the acetabulum are absent. Function at maturity is primarily dependent upon the extent of the
leg-length discrepancy (Koman et al. 1982; Panting
and Williams 1978; Kalamchi et al. 1985; Gillespie
and Torode 1983). When femoral focal dysplasia
occurs in association with skeletal abnormalities involving the upper extremities, a highly specific pattern of rare arm defects is found, such as amelia, peromelia at the lower end of the humerus, humeroradial synostosis, and defects of the ulna and ulnar
320
Chapter 5 · Long Bones
rays (Kuhne et al. 1967). For such cases, in which
femoral, fibular, and/or ulnar defects tend to be associated, the term femur-fibula-ulna syndrome (FFU
complex, OMIM 228200) has been proposed (Lenz et
al. 1993). The limb malformations present in the FFU
complex are different from those seen in most other
types of limb defects. Neither familial occurrence nor
associated exogenous factors have been identified.
Some evidence favors early somatic mutation (Lenz
et al. 1993). The FFU complex has similarities with
another pattern of malformations, which includes
aplasia/hypoplasia of the ulnas, hypoplasia of the
pelvis, aplasia/hypoplasia of the femurs, fibular aplasia, and variable digital abnormalities, as well as absent/dysplastic nails (OMIM 601849) (Kumar et al.
1997). Overlap is also recognized with Fuhrmann
syndrome (228930) and with Al-Awadi/Raas-Rothschild syndrome (276820). The FFU complex is a separate entity from femorofacial syndrome (OMIM
134780), a rare disorder with bilateral femoral hypoplasia/aplasia and a characteristic facies (short
nose with elongated philtrum, thin upper lip, micrognathia, upslanting palpebral fissure, cleft palate and
ear deformities) that also has similarities with the
caudal regression syndrome (Daentl et al. 1975;
Gleiser et al. 1978). Hypoplasia of both acetabula and
short or hypoplastic fibulas are additional consistently found features of this disorder.
Radiographic Synopsis
AP, LL, and axial projections. The full extent of hip
instability may not be ascertained on radiographs
obtained during the 1st year of life (Schatz and Kopits 1978). Objective radiographic criteria include assessment of femoral length, acetabular depth, and
shape of the proximal femur (Hillmann et al. 1987).
1. Relatively normal acetabulum and capital femoral
epiphysis; dysplastic proximal femoral shaft; short
femur; subtrochanteric varus deformity or pseudarthrosis; relatively normal distal end of the femur
[proximal femoral focal dysplasia, mild cases
(classes A and B)]
2. Stunted, severely shortened femur with a clubshaped or pointed proximal end; unossified gap
between epiphysis and femoral shaft; varying degrees of acetabular and pelvic dysplasia [proximal
femoral focal dysplasia, severe cases (classes C
and D)]
Associations
• Isolated focal femoral dysplasia
• Femur-fibula-ulna syndrome (FFU complex)
• Splenogonadal fusion-limb defect syndrome
References
Bryant DD 3rd, Epps CH Jr. Proximal femoral focal deficiency:
evaluation and management. Orthopedics 1991; 14: 775–84
Daentl DL, Smith DW, Scott CI, Hall BD, Gooding CA. Femoral
hypoplasia-unusual facies syndrome. J Pediatr 1975; 86:
107–11
Gillespie R, Torode IP. Classification and management of congenital abnormalities of the femur. J Bone Joint Surg Br
1983; 65: 557–68
Gleiser S, Weaver DD, Escobar V, Nichols G, Escobedo M.
Femoral hypoplasia-unusual facies syndrome, from another viewpoint. Eur J Pediatr 1978; 128: 1–5
Goldman AB, Schneider R, Wilson PD Jr. Proximal focal
femoral deficiency. J Can Assoc Radiol 1978; 29: 101–7
Gouw ASH, Elema JD, Bink-Boelkens MT, de Jongh HJ, ten Kate
LP. The spectrum of splenogonadal fusion. Case report and
review of 84 reported cases. Eur J Pediatr 1985; 144: 316–23
Hillmann JS, Mesgarzadeh M, Revesz G, Bonakdarpour A,
Clancy M, Betz RR. Proximal femoral focal deficiency: radiologic analysis of 49 cases. Radiology 1987; 165: 769–73
Kalamchi A, Cowell HR, Kim KI. Congenital deficiency of the
femur. J Pediatr Orthop 1985; 5: 129–34
Koman LA, Meyer LC, Warren FH. Proximal femoral focal deficiency: a 50-year experience. Dev Med Child Neurol 1982;
24: 344–55
Kuhne D, Lenz W, Petersen D, Schonenberg H. Defekt von Femur
und Fibula mit Amelie, Peromelie oder ulnaren Strahldefekten der Arme. Ein Syndrom. Humangenetik 1967; 3: 244–63
Kumar D, Duggan MB, Mueller RF, Karbani G. Familial aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal digits in an inbred Pakistani Muslim family: a possible
new autosomal recessive disorder with overlapping manifestations of the syndromes of Fuhrmann, Al-Awadi, and
Raas-Rothschild. Am J Med Genet 1997; 70: 107–13
Lange DR, Schoenecker PL, Baker CL. Proximal femoral focal
deficiency: treatment and classification in forty-two cases.
Clin Orthop 1978; 135: 15–25
Lenz W, Zygulska M, Horst J. FFU complex: an analysis of 491
cases. Hum Genet 1993; 91: 347–56
Levinson ED, Ozonoff MB, Royen PM. Proximal femoral focal
deficiency (PFFD) Radiology 1977; 125: 197–203
Panting AL, Williams PF. Proximal femoral focal deficiency.
J Bone Joint Surg Br 1978; 60: 46–52
Schatz SL, Kopits SE. Proximal femoral focal deficiency. AJR
Am J Roentgenol 1978; 131: 289–95
Stormer SV. Proximal femoral focal deficiency. Orthop Nurs
1997; 16: 25–31
Tibial Bowing
䉴 [Angulation of the tibia]
This section has significant overlap with the section
“Bowed Tubular Bones” in this chapter. Most of the
general comments provided in that section apply to
tibial bowing, including the fact that bowing can be
congenital or acquired; confined to the tibia or extended to other long bones; related to a focal defect,
Abnormalities of the Long Bones in the Lower Extremities
Fig. 5.32. Neurofibromatosis type 1 in a 2-year-old child. Observe anterolateral bending of the distal end of the left tibia
and, to a lesser extent, of the fibula. Bowing deformities can either precede or follow pseudarthrosis, or can exist as a manifestation of the disease in the absence of bone discontinuity.
(Courtesy of Dr. P. Balestrazzi, University of Parma, Italy)
or part of a systemic disorder. In this section, the
conditions with selective or preferential involvement
of the tibia are briefly reviewed.
Unilateral tibial bowing in children may be seen
after plastic bending fractures of the tibial shaft, or after injuries to the epiphysis, whether traumatic or infectious in origin. In the first case bowing is typically
transitory, while in the second case it tends to be permanent. Unilateral, congenital tibial bowing may be
secondary to a faulty intrauterine position or be the
result of congenital pseudarthrosis. Bowing deformities related to faulty intrauterine positions tend to resolve spontaneously over time (Reed 1992), while
those secondary to congenital pseudarthrosis do not.
The term ‘pseudarthrosis’ refers to discontinuity of
the bone, which is characterized by nonunion and abnormal bending at the site. Mechanisms underlying
congenital pseudarthrosis include abnormalities of
the primary cartilaginous anlage, trauma, amniotic
bands, genetic causes, vascular anomalies, and metabolic and nutritional disturbances (Newell and
Durbin 1976). However, the ultimate reason for bony
321
nonunion often remains obscure. Congenital
pseudarthrosis has been related to the presence of
neurofibromatosis type 1 (OMIM 162220) in about
50% of cases (Brown et al. 1977) (Fig. 5.32). Hence,
whenever pseudarthrosis of the tibia is found, neurofibromatosis type 1 must be excluded. Since an
intraosseous neurofibroma or schwannoma at the site
of nonunion is found only rarely, the bony defect
probably reflects abnormal or deficient bone formation of the basic mesodermal dysplasia (Andersen
1976). In under 20% of cases pseudarthrosis has been
related to the presence of fibrous dysplasia and fibrous
tissue has been found at the site of the fracture
(Brown et al. 1977). The lesion usually develops during the first 2 years of life, although cases of later onset have been observed. Fibular bowing and limb
length discrepancy can be associated features (Swischuk and John 1995). In another 30% of cases neither
neurofibromatosis nor fibrous dysplasia can be documented (Brown et al. 1977). Pseudarthrosis can also
occur with osteofibrous dysplasia, a benign fibro-osseous lesion of bone similar to fibrous dysplasia, with
selective involvement of the tibia and fibula (Campanacci and Laus 1981). Involvement of other bones,
notably the ulna, is rare (Goto et al. 2001). Cortical irregularities with alternating lytic and sclerotic lesions
are seen radiographically. Spontaneous resolution is
common in the long term, and surgical removal is indicated only in patients with a high risk of impending
fracture and progressive deformity (Ozaki et al.
1998). The lesions tend to recur after surgery. The differential diagnosis against fibrous dysplasia is based
on lesion location (maxilla, frontal bone, and femur in
fibrous dysplasia; tibia and fibula in osteofibrous dysplasia), patient age (on average 24.0 years for fibrous
dysplasia; 13 years for osteofibrous dysplasia), and
histological appearance (resting osteoblasts and cartilage differentiation in fibrous dysplasia; fibroblastlike spindle cells, and osseous tissue in osteofibrous
dysplasia) (Maki et al. 2001). A possible involvement
of neurofibromin, the product of the tumor suppressor NF1 (neurofibromatosis type 1) gene in the development of osteofibrous dysplasia, has been suggested
(Sakamoto et al. 2001).
Bilateral tibial bowing may occur in isolation or,
more commonly, in association with other defects,
including fibular hemimelia, shortening of the ipsilateral femur, equinovalgus deformity of the foot, deficiency of the lateral rays in the foot, and tarsal coalition (Hootnick et al. 1977). With isolated tibial bowing, the tibial convexity is usually posteromedial,
dorsiflexion deformity of the foot may be present,
and bowing of the fibula commonly coexists. In the
322
Chapter 5 · Long Bones
case of fibular hemimelia, the tibia is usually bowed
in a ventral and medial direction. Tibial bowing occurs in the context of disorders characterized by inherent bone weakening, including rickets and osteomalacia. In osteogenesis imperfecta (OMIM 166200,
166210, 166220, 259420) both osteomalacia and multiple fractures can be responsible for tibial bowing.
Bilateral bowing of the tibias and fibulas, often associated with bowing of other tubular bones, is typically encountered in the autosomal dominant Weismann-Netter-Stuhl syndrome (OMIM 112350) (Francis et al. 1991). As in neurofibromatosis type 1, tibial
curvature is anterior and medial and is associated
with thickening of the posterior tibial cortex. However, ‘tibialization’ of the fibula in Weismann-NetterStuhl syndrome is clearly different from the gracile
and hypoplastic fibular appearance in neurofibromatosis type 1. In Melnick-Needles syndrome (OMIM
309350), lateral bowing of both tibias, with a characteristic S-shaped configuration, is striking (Melnick
and Needles 1966).
Radiographic Synopsis
AP and LL projections.
1. Posteromedial convexity; dorsiflexion deformity
of the foot (isolated tibial bowing)
2. Anteromedial angulation; shortening of the ipsilateral femur; equinovalgus deformity of the foot;
deficiency of the lateral rays in the foot; tarsal
coalition (fibular hemimelia)
3. Anterior and medial or lateral angulation of the
tibia (sometimes associated with fibular angulation), most commonly at the junction between the
middle and distal portion; tibial shortening; radiolucent segment or pseudocystic lesion at the apex
of bowing; fracture and deformity; cupping of
proximal end and sclerosis of distal end (congenital pseudarthrosis)
4. Uni- or bilateral tibial bowing; lytic and sclerotic
lesions within the cortex (osteofibrous dysplasia)
5. Anteromedial bowing of both tibias; thickening of
the posterior tibial cortex; wide and large fibulas;
bowing of other long bones (Weismann-NetterStuhl syndrome)
6. Lateral, S-shaped bowing deformity of tibias; bowing of other long bones (Melnick-Needles syndrome)
Associations
• Bending fractures
• Campomelic dysplasia
• Fibrous dysplasia
• Fibular aplasia/hypoplasia
• Hyperphosphatemia
•
•
•
•
•
•
•
•
•
•
•
Hypophosphatasia
Infection
Irradiation
Melnick-Needles syndrome
Neurofibromatosis type 1
Osteofibrous dysplasia
Osteogenesis imperfecta
Osteomalacia
Rickets
Trauma
Weismann-Netter-Stuhl syndrome
References
Andersen KS. Congenital pseudarthrosis of the leg: late results.
J Bone Joint Surg Am 1976; 58: 657–62
Brown GA, Osebold WR, Ponseti IV. Congenital pseudarthrosis
of long bones. A clinical, radiographic, histologic, and
ultrastructural study. Clin Orthop 1977; 128: 228–42
Campanacci M, Laus M. Osteofibrous dysplasia of the tibia and
fibula. J Bone Joint Surg Am 1981; 63: 367–75
Francis GL, Jelinek JJ, McHale K et al. The Weismann-Netter
syndrome: a cause of bowed legs in childhood. Pediatrics
1991; 88: 334–7
Goto T, Kojima T, Iijima T, Yokokura S, Kawano H, Yamamoto
A, Matsuda K. Osteofibrous dysplasia of the ulna. J Orthop
Sci 2001; 6: 608–11
Hootnick D, Boyd NA, Fixsen JA, Lloyd-Roberts GC. The natural history and management of congenital short tibia with
dysplasia or absence of the fibula. J Bone Joint Surg Br 1977;
59: 267–71
Maki M, Saitoh K, Horiuchi H, Morohoshi T, Fukayama M,
Machinami R. Comparative study of fibrous dysplasia and
osteofibrous dysplasia: histopathological, immunohistochemical, argyrophilic nucleolar organizer region and
DNA ploidy analysis. Pathol Int 2001; 51: 603–11
Melnick JC, Needles CF. An undiagnosed bone dysplasia. A 2
family study of 4 generations and 3 generations. Am J
Roentgenol Radium Ther Nucl Med 1966; 97: 39–48
Newell RLM, Durbin FC. The aetiology of congenital angulation of tubular bones with constriction of the medullary
canal and its relationship to congenital pseudarthrosis.
J Bone Joint Surg Br 1976; 58: 444–7
Ozaki T, Hamada M, Sugihara S, Kunisada T, Mitani S, Inoue H.
Treatment outcome of osteofibrous dysplasia. J Pediatr
Orthop B 1998; 7: 199–202
Reed MH. Pediatric skeletal radiology. Williams & Wilkins,
Baltimore, 1992, p. 389
Sakamoto A, Oda Y, Oshiro Y, Tamiya S, Iwamoto Y, Tsuneyoshi
M. Immunoexpression of neurofibromin, S-100 protein,
and leu-7 and mutation analysis of the NF1 gene at codon
1423 in osteofibrous dysplasia. Hum Pathol 2001; 32:
1245–51
Swischuk LE, John SD. Differential diagnosis in pediatric radiology. Williams & Wilkins, Baltimore, 1995, p. 203
Abnormalities of the Long Bones in the Lower Extremities
323
Fig. 5.33 a, b. Congenital deficiency of the tibia and fibula
in a 5-month-old girl. Note bilateral absence of the tibia and
fibula, with well-developed femurs and feet. This phenotype
is extremely rare. (From Yasui
et al. 2000)
a
Tibial Hemimelia
䉴 [Longitudinal deficiency of the tibia]
Longitudinal defects of the tibia range from mild
hypoplasia to complete absence. Based on the radiographic appearance, four types of tibial hemimelia
have been recognized (Schoenecker et al. 1989): type
1, characterized by absent tibia and distally hypoplastic femur; type 2, in which the tibia is distally
deficient and well developed proximally; type 3, in
which the tibia is proximally deficient and well ossified distally; and type 4, characterized by shortening
of the distal tibia, with diastasis of the ankle and normally developed proximal tibia.
Bilateral aplasia of the tibia can be an isolated anomaly in otherwise normal individuals (tibial hemimelia, OMIM 275220) (Emami-Ahari and Mahloudji
1974; McKay et al. 1984). However, it occurs most commonly in association with other congenital defects, including proximal femoral focal deficiency, fibular
hemimelia (Fig. 5.33a,b), congenital dislocation of the
hip, and coxa valga, or as part of broader syndromes.
Distinct malformation spectra are now emerging
in which tibial hemimelia occurs in association with
split hand/split foot (Richieri-Costa et al. 1987), cleft
lip/palate (Richieri-Costa 1987), and Langer-Giedion
syndrome (Stevens and Moore 1999; Turleau et al.
1982). In tibial hemimelia with split hand/split foot
(cleft hand/tibial hemimelia, OMIM 119100) malformations may include distal hypoplasia or bifurcation
of the femurs, hypo- or aplasia of the ulnas, and
minor anomalies such as aplasia of the patellae, hypoplastic big toes, and cup-shaped ears. Its inheri-
b
tance is most probably autosomal dominant, with
reduced penetrance (Sener et al. 1989). Particular
interest attaches to the association with LangerGiedion syndrome (OMIM 150230), which has suggested that a gene involved in limb development is
located in the 8q24.1 region. Its deletion might cause
tibial hemimelia (Stevens and Moore 1999). Bilateral
tibial hypoplasia with polydactyly (OMIM 188770) of
hands and feet has also been reported (Eaton and
McKusick 1969; Canki 1980). This may be the same
trait as the condition referred to as ‘tibial absence
with polydactyly’ (OMIM 188740). Triphalangeal
thumb and syndactyly are consistent features in this
syndrome. Significant variability of the clinical manifestations has been noted (Kantaputra and Chalidapong 2000). In acromelic frontonasal dysplasia
(OMIM 603671), a rare variant of frontonasal dysplasia, the characteristic craniofacial anomalies are
associated with central nervous system malformations and limb defects, including tibial hypoplasia/
aplasia, talipes equinovarus, and preaxial polydactyly of the feet (Kantaputra and Chalidapong 2000;
Toriello et al. 1986; Verloes et al. 1992). The inheritance pattern is possibly autosomal recessive. The
frontonasal malformations have some overlap with
acrocallosal (OMIM 200990) and Greig (OMIM
175700) syndromes, but are distinguished from them
by the significant hypertelorism and bifid nasal tip.
Radiographic Synopsis
AP and LL projections. The femur, fibula and ankle
must be investigated.
1. Tibial hemimelia (familial isolated tibial hemimelia)
324
Chapter 5 · Long Bones
2. Tibial hemimelia; cleft hand and foot; hypoplasia
or bifurcation of the distal femur; patellar aplasia
(tibial hemimelia with split hand/split foot)
3. Tibial hypoplasia; hand and foot polysyndactyly;
triphalangeal thumb (tibial hemimelia/polysyndactyly/triphalangeal thumb syndrome)
4. Tibial hypoplasia/aplasia; craniofacial anomalies;
CNS malformations (acromelic frontonasal dysplasia)
Associations
• Cleft hand/tibial hemimelia
• Duplication of fibula and ulna, with absent tibia
and radius
• Faciocardiomelic dysplasia, lethal
• Familial isolated tibial hemimelia
• Mesomelic dysplasias
• Tibial hemimelia/polysyndactyly/
triphalangeal thumb
• Tibial hemimelia/micromelia/trigobrachycephaly
syndrome
References
Canki N. Syndactylie, polydactylie et absence de pouces associées a une hypoplasie du tibia et une anomalie du nez dans
deux générations: un nouveau syndrome. Rev Med Liege
1980; 35: 464–7
Eaton GO, McKusick VA. A seemingly unique polydactyly-syndactyly syndrome in four persons in three generations.
Birth Defects Orig Art Ser 1969; 3: 221–5
Emami-Ahari Z, Mahloudji M. Bilateral absence of the tibias in
three sibs. Birth Defects Orig Art Ser 1974; 5: 197–200
Kantaputra PN, Chalidapong P. Are triphalangeal thumb-polysyndactyly syndrome (TPTPS) and tibial hemimeliapolysyndactyly-triphalangeal thumb syndrome (THPTTS)
identical? A father with TPTPS and his daughter with
THPTTS in a Thai family. Am J Med Genet 2000; 93: 126–31
McKay M, Clarren SK, Zorn R. Isolated tibial hemimelia in
sibs: an autosomal-recessive disorder? Am J Med Genet
1984; 17: 603–7
Richieri-Costa A, Ferrareto I, Masiero D, da Silva CRM. Tibial
hemimelia: report on 37 new cases, clinical and genetic
considerations. Am J Med Genet 1987; 27: 867–84
Richieri-Costa A. Tibial hemimelia-cleft lip/palate in a Brazilian child born to consanguineous parents. Am J Med Genet
1987; 28: 325–9
Schoenecker PL, Capelli AM, Millar EA, Sheen MR, Haher T,
Aiona MD, Meyer LC. Congenital longitudinal deficiency of
the tibia. J Bone Joint Surg Am 1989; 71: 278–87
Sener RN, Isikan E, Diren HB, Sayli BS, Sener F. Bilateral splithand with bilateral tibial aplasia. Pediatr Radiol 1989; 19:
258–60
Stevens CA, Moore CA. Tibial hemimelia in Langer-Giedion
syndrome-possible gene location for tibial hemimelia at
8q. Am J Med Genet 1999; 85: 409–12
Toriello HV, Radecki LL, Sharda J, Looyenga D, Mann R. Frontonasal ‘dysplasia,’ cerebral anomalies, and polydactyly: report of a new syndrome and discussion from a developmental field perspective. Am J Med Genet 1986; 2: 89–96
Turleau C, Chavin-Colin F, de Grouchy J, Maroteaux P, Rivera
H. Langer-Giedion syndrome with and without del 8q: assignment of critical segment to 8q23. Hum Genet 1982; 62:
183–7
Verloes A, Gillerot Y, Walczak E, Van Maldergem L, Koulischer
L. Acromelic frontonasal ‘dysplasia’: further delineation
of a subtype with brain malformation and polydactyly
(Toriello syndrome). Am J Med Genet 1992; 42: 180–3
Fibular Hemimelia
䉴 [Longitudinal deficiency of the fibula]
Fibular deficiency is a common congenital defect that
can occur as a single defect or as part of any of a
number of syndromic and nonsyndromic conditions. Therefore, fibular hypoplasia/aplasia alone is
not of much help in the recognition of specific disorders. Fibular deficiencies may be uni- or bilaterally
distributed and can vary in severity from mild hypoplasia to aplasia (Reed 1992; Grogan et al. 1987;
Achterman and Kalamchi 1979; Jansen and Andersen
1974). Varying degrees of shortening and bowing of
the companion tibia with limb length discrepancy
often coexist, depending on the severity of the fibular
defect (Fordham et al. 1999). When the fibula is absent, shortening and ventromedial bowing of the tibia are common. Distal and proximal deficiencies are
encountered. Distal fibular hypoplasia is more commonly associated with valgus deformity of the ankle,
whereas proximal deficiency more often occurs in
association with valgus deformity of the knee and
instability at the proximal tibiofibular articulation
(Ogden 1984). Several other abnormalities can occur
in association with fibular hypoplasia/aplasia,
including proximal femoral focal deficiency, femoral hypoplasia, coxa vara, ball-and-socket ankle
joint, equinovalgus deformity of the foot, tarsal coalition, and deficiency of the lateral tarsal bones and lateral rays in the foot (Maffulli and Fixsen 1991)
(Fig. 5.34a,b).
The association of fibular aplasia/hypoplasia,
femoral bowing, and poly-, syn-, and oligodactyly,
has been termed Fuhrmann syndrome (OMIM 228930)
(Fuhrmann et al. 1980). Pelvic hypoplasia, congenital
hip dislocation, and absence or coalescence of the
tarsal bones are additional findings. A peculiar constellation of abnormalities, sharing similarities with
the syndromes of Fuhrmann and Al-Awadi/Raas-
Abnormalities of the Long Bones in the Lower Extremities
325
Fig. 5.34 a,b. Fibular hemimelia. a In a 7-year-old boy: complete absence of the right fibula, with tibial shortening, and
severe equinovalgus deformity of the foot. b In a 4-year-old
boy: fibular aplasia, tibial hypoplasia, valgus deformity of
the ankle joint, and deficiency
of the lateral tarsal bones and
lateral rays in the foot
a
Rothschild (OMIM 276820), includes aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal
digits and nails (OMIM 601849) (Kumar et al. 1997).
The femur-fibula-ulna syndrome (FFU complex,
OMIM 228200) is a malformation complex in which
fibular, femoral, and ulnar deficiencies tend to be associated (Kuhne et al. 1967). Overlap is recognized with
the Fuhrmann syndrome, the Al-Awadi/Raas-Rothschild syndrome, and the malformation spectrum of
“aplasia/hypoplasia of pelvis, femur, fibula, and ulna
with abnormal digits and nails” mentioned above.
Fibular agenesis, together with radial shortening and
coalescence of the tarsal bones, has been reported in a
girl with oro-facio-digital syndrome, type I (OMIM
311200) (Figuera et al. 1993), in which typical features
are telecanthus, flat nasal bridge, retrognathia, cleft
palate, oligodactyly, and preaxial polydactyly.
Fibular aplasia with craniosynostosis (OMIM
218550) is a well-recognized association (Lowry 1972).
A wider spectrum of anomalies also includes radial
defects and cleft lip/palate (Ladda et al. 1978). Fibular
aplasia and brachydactyly is another well-established
association. Brachydactyly can either be complex (Du
Pan syndrome, OMIM 228900), consisting of metacarpal shortening, trapezoid middle phalanx of the
index finger with radial deviation, small carpals,
short and laterally deviated toes, and tibiotarsal dislocation (Ahmad et al. 1990), or a combination of
brachydactyly in the hands and ectrodactyly (split
deformity) in the feet (OMIM 113310) (Genuardi et
al. 1990). A unique combination of brachydactyly,
severely delayed bone maturation, spinal and pelvic
b
abnormalities, short stature, and bilateral fibular hypoplasia has been reported (Castriota-Scanderbeg et
al. 1999). Another combination of anomalies involves
extremely short digits with hypoplasia/aplasia of
proximal and middle phalanges in the fingers and
toes, short stature, bilateral deficiency of fibulas, and
normal intelligence (Kohn et al. 1989).
Radiographic Synopsis
AP and LL projections. The radiographic survey aims
at assessing the presence of the fibular defect, its location (proximal or distal), degree of severity (minimal
hypoplasia, type I; complete absence, type II), and the
presence of any associated abnormalities. Osteochondral and extraosseous abnormalities, which may be
relevant in the planning of surgical or rehabilitation
treatments, escape direct visualization on conventional radiography but are well depicted on MR imaging (Laor et al. 1996). The normal proximal fibular physis is usually situated 5–10 mm distal to the tibial physis (Ogden 1984). Proximal fibular hypoplasia is
established when the fibular head lies well below the
tibial growth plate. The distal fibular physis is normally at the level of the tibial articular surface or just
distal to it (Ogden and McCarthy 1983). Distal fibular
hypoplasia is established when the distal fibular
growth plate lies cephalad to the talar dome.
1. Fibular aplasia/hypoplasia; femoral bowing; pelvic
hypoplasia; finger/toe anomalies (Fuhrmann syndrome)
2. Aplasia/hypoplasia of fibula, femur, and ulna (femur-fibula-ulna syndrome)
326
Chapter 5 · Long Bones
Associations
• Acro-fronto-facio-nasal dysostosis syndrome
• Atelosteogenesis II (de la Chapelle syndrome)
• Boomerang dysplasia
• Brachydactyly-ectrodactyly/fibular aplasia or hypoplasia
• Campomelic dysplasia
• Chondroectodermal dysplasia (Ellis van Creveld)
• Chromosomal abnormalities
• Craniosynostosis/fibular aplasia
• Craniosynostosis/radial defects
• Du Pan syndrome
(fibular aplasia/complex brachydactyly)
• Facio-auriculo-radial dysplasia
• Faciocardiomelic dysplasia, lethal
• Femur-fibula-ulna syndrome
• Fibular aplasia or hypoplasia/femoral bowing/
poly-, syn-, and oligodactyly
(Fuhrmann syndrome)
• Grebe chondrodysplasia
• Limb deficiency/heart malformation syndrome
• Mietens-Weber syndrome
• Ophthalmo-mandibulo-melic dysplasia
• Oro-facio-digital syndrome with fibular aplasia
• Oto-onycho-peroneal syndrome
• Roberts syndrome
• Schneckenbecken dysplasia
• Seckel syndrome
• Ulnar-mammary syndrome
• Weyers ulnar ray/oligodactyly syndrome
Grogan DP, Love SM, Ogden JA. Congenital malformations of
the lower extremities. Orthop Clin North Am 1987; 18:
537–54
Jansen K, Andersen KS. Congenital absence of the fibula. Acta
Orthop Scand 1974; 45: 446–53
Kohn G, Veder M, Schoenfeld A, El Shawwa R. New type of
autosomal recessive short-limb dwarfism with absent fibulae, exceptionally short digits, and normal intelligence. Am
J Med Genet 1989; 34: 535–40
Kuhne D, Lenz W, Petersen D, Schonenberg H. Defekt von
Femur und Fibula mit Amelie, Peromelie oder ulnaren
Strahldefekten der Arme. Ein Syndrom. Humangenetik
1967; 3: 244–63
Kumar D, Duggan MB, Mueller RF, Karbani G. Familial aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal digits in an inbred Pakistani Muslim family: a possible
new autosomal recessive disorder with overlapping manifestations of the syndromes of Fuhrmann, Al-Awadi, and
Raas-Rothschild. Am J Med Genet 1997; 70: 107–13
Ladda RL, Stoltzfus E, Gordon SL, Graham WP. Craniosynostosis associated with limb reduction malformations and cleft
lip/palate: a distinct syndrome. Pediatrics 1978; 61: 12–5
Laor T, Jaramillo D, Hoffer FA, Kasser JR. MR imaging in congenital lower limb deformities. Pediatr Radiol 1996; 26:
381–7
Lowry RB. Congenital absence of the fibula and craniosynostosis in sibs. J Med Genet 1972; 9: 227–9
Maffulli N, Fixsen JA. Fibular hypoplasia with absent lateral
rays of the foot. J Bone Joint Surg Br 1991; 73: 1002–4
Ogden JA. Radiology of postnatal skeletal development. IX.
Proximal tibia and fibula. Skeletal Radiol 1984; 11: 169–77
Ogden JA, McCarthy SM. Radiology of postnatal skeletal development. VIII. Distal tibia and fibula. Skeletal Radiol 1983;
10: 209–20
Reed MH. Pediatric Skeletal Radiology. Baltimore: Williams &
Wilkins, 1992: 384
References
Patellar Hypoplasia, Aplasia, Dysplasia,
and Dislocation
Achterman C, Kalamchi A. Congenital deficiency of the fibula.
J Bone Joint Surg Br 1979; 61: 133–7
Ahmad M,Abbas H,Wahab A, Haque S. Fibular hypoplasia and
complex brachydactyly (Du Pan syndrome) in an inbred
Pakistani kindred. Am J Med Genet 1990; 36: 292–6
Castriota-Scanderbeg A, Zelante L, Masala S, Gasparini P,
Lachman RS. Acrodysplasia, severe ossification abnormalities with short stature, and fibular hypoplasia. Am J Med
Genet 1999; 84: 68–73
Figuera LE, Rivas F, Cantu JM. Oral-facial-digital syndrome with
fibular aplasia: a new variant. Clin Genet 1993; 44: 190–2
Fordham LA, Applegate KE, Wilkes DC, Chung CJ. Fibular
hemimelia: more than just an absent bone. Semin Musculoskelet Radiol 1999; 3: 227–38
Fuhrmann W, Fuhrmann-Rieger A, de Sousa F. Poly-, syn- and
oligodactyly, aplasia or hypoplasia of fibula, hypoplasia of
pelvis and bowing of femora in three sibs-a new autosomal
recessive syndrome. Eur J Pediatr 1980; 133: 123–9
Genuardi M, Zollino M, Bellussi A, Fuhrmann W, Neri G.
Brachy-/ectrodactyly and absence or hypoplasia of the
fibula: an autosomal dominant condition with low penetrance and variable expressivity. Clin Genet 1990; 38: 321–6
䉴 [Small, absent, abnormally shaped
and displaced patella]
Patellar hypoplasia/aplasia is found as an isolated
anomaly in familial aplasia/hypoplasia of the patella
(OMIM 168860), a rare autosomal dominant disorder
with the gene responsible mapping to the 17q21-q22
region (Mangino et al. 1999). It is also found as one
of the features of a selected number of syndromes and skeletal dysplasias, including nail-patella
syndrome, Meier-Gorlin syndrome, ischiopatellar
dysplasia, and certain mesomelic dysplasias. In
nail-patella syndrome (onycho-osteodysplasia,
OMIM 161200), an autosomal dominant disorder,
the skeletal abnormalities, notably patellar hypoplasia/aplasia and posterior iliac horns, are highly
characteristic, allowing radiographic diagnosis
even in cases in which the disease has not been sus-
Abnormalities of the Long Bones in the Lower Extremities
pected clinically (Williams and Hoyer 1973). The
malformation spectrum of the ear/patella/
short stature syndrome (Meier-Gorlin syndrome,
OMIM 224690) includes microtia, absent patellae,
short stature, a characteristic facies, micrognathia, elbow dislocation, slender ribs and long bones, hooked
clavicles, clinodactyly, camptodactyly, bone age retardation, Blount disease, and bilateral aseptic necrosis of the lateral femoral condyles. Affected patients
are severely deaf and mentally retarded (Gorlin et al.
1975; Cohen et al. 1991; Loeys et al. 1999). Ischiopatellar dysplasia (small patella syndrome, OMIM
147891) is an autosomal dominant condition in
which small patellas are associated with defective ossification at the ischiopubic junction and foot malformations (ball-and-socket ankle joints, pes planus,
tarsal coalition, calcaneal exostoses, and metatarsal
shortening). Recurrent dislocation of the hypoplastic
patella is a frequent complication. No iliac horn or
fingernail changes have been described in this condition. Thus, this entity is clearly distinct from the nailpatella syndrome (Scott and Taor 1979). Hypoplastic
or absent patella is also a feature in mesomelic dysplasia, Werner type (OMIM 188770) and hypoplastic
tibia-radius type (OMIM 156230). These autosomal
dominant disorders display similar radiographic features, with bilateral tibial aplasia or hypoplasia, absent thumbs, and polydactyly or syndactyly in the
hands and feet (Pashayan et al. 1971; Leroy 1975). The
most striking features of the hypoplastic tibia-radius
type are hypoplasia of the tibia and radius, with
pseudarthrosis of the tibia and relative elongation of
the fibula (Leroy 1975). The pterygium syndromes
encompass a heterogeneous group of conditions,
with either autosomal dominant or recessive inheritance, characterized by the presence of one or several
webs (pterygia) in the body. In the autosomal dominant popliteal pterygium syndrome (OMIM 119500)
the web crosses the popliteal fossa, extending from
the hip to the heel in some cases. Skeletal anomalies
include hypoplasia or aplasia of digits, syndactyly,
tibial hypoplasia, talipes equinovarus, vertebral and
rib anomalies, and aplastic patellas. Cleft lip/palate,
genitourinary anomalies, and mental retardation are
further features (Escobar and Weaver 1978).
Changes in the shape of the patella can either be
specific to a given disorder or devoid of any clinical
significance. Since the patella ossifies from multiple
foci, irregularity of its contour is a normal finding in
the developing skeleton. Another common anatomical variant, occurring in about 2% of the normal
adult population, is the bipartite patella, resulting
from failure of one ossification focus to fuse with the
327
Fig. 5.35. Patella bipartita in an adult patient. Note the ossicle
at the superolateral edge, which is not fused with the main corpus of the patella
remainder of the bone. The unfused ossicle, most
commonly located at the superolateral edge, is identified as a small bony fragment lined with cartilage
both on the articular surface and on the surface facing the main corpus of the patella (Fig. 5.35). A patella bipartita can be unilateral or bilateral and is mostly asymptomatic. Occasionally, local pain has been
reported (Green 1975). Multipartite patella originates from multiple unfused bony foci. A finding
similar, and probably related, to patella bipartita is
dorsal defect of the patella. Just like bipartite patella,
this small defect is most frequently found on the
superolateral aspect of the patella and can have a unilateral or a bilateral distribution. It appears as a wellcircumscribed defect in which fibrous tissue with or
without signs of bone necrosis can be seen. A traumatic mechanism related to traction at the insertion
of the muscle vastus lateralis has been suggested (van
Holsbeeck et al. 1987). The defect heals spontaneously in most cases, being filled in with sclerotic bone
and reconstituted as a normal patella thereafter. A
nonunion fracture of the patella can produce a radiographic appearance indistinguishable from that of
bipartite patella. A special form of bipartite patella is
the double-layered patella, consisting of a partition
on the frontal plane with resultant anterior and posterior components. This anomaly is consistently
associated with multiple epiphyseal dysplasia (OMIM
132400) and has not been described in other dysplasias (Dahners et al. 1982; Sheffield 1998; Gardner
et al. 1999). In addition to being ‘double layered,’ the
patella is hypoplastic and predisposed to subluxation
328
Chapter 5 · Long Bones
or dislocation. Multiple epiphyseal dysplasia is a
group of genetically heterogeneous disorders. In
most cases a pattern of autosomal dominant inheritance is observed, but examples of spontaneous
mutation and pedigrees with autosomal recessive
inheritance have also been reported. In one of these
reports, the index patient, who had a homozygous R279 W mutation in the DTDST gene product,
was born to healthy parents who were heterozygous
for that mutation and had normal stature, clubfoot,
and double-layered patellas (Superti-Furga et al.
1999).
Dislocation of the patella can occur acutely in normal individuals, often after a twisting trauma with
the knee in flexion. Injuries to the medial patella
facet, lateral femoral condyle, and medial retinaculum are commonly associated (Frandsen and Kristensen 1979). In other individuals, a minor trauma is
enough to cause acute patellar dislocation, followed
by a tendency to recurrent dislocations in subsequent
months or years. Except for a generic ‘increased vulnerability’ to patellar dislocation, these individuals
are normal in all respects. Several factors have been
implicated in the development of patellar instability,
including variations in patellar shape, smallness
of the lateral femoral condyle, shallowness of the
patellofemoral groove, genu valgum, defective insertion of the infrapatellar ligament, and laxity of the
supporting structures (Bensahel et al. 2000; Eilert
2001). Another factor predisposing to patellar dislocation is an abnormally high or low position of
the patella relative to the joint line (Insall et al. 1972).
A high patella (patella alta) has been associated
with patellar chondromalacia (OMIM 168900) and
Sinding-Larsen-Johansson disease (Brattstrom 1970;
David-Chausse and Vignes 1982). The association of
patellar chondromalacia with recurrent dislocation
of the patella (169000) is well known, but there is
some uncertainty as to whether the recurrent dislocation causes patellar chondromalacia, or the other
way round (Rubacky 1963). An abnormally low patella (patella baja) is found in achondroplasia (OMIM
100800), in neuromuscular disorders, including poliomyelitis, and after surgical interventions with displacement of the tibial tuberosity (Sakai et al. 1993).
Lateral dislocation is more common, but vertical
and medial displacements do also occur. Recurrent
dislocation of the patella has been observed in several members of the same family over multiple generations (familial recurrent patella dislocation,
OMIM 169000) (Miller 1978). This probably autosomal dominant trait is independent of familial joint
laxity (Carter and Sweetnam 1960). Instances of
male-to-male transmission have been reported
(Borochowitz et al. 1988). Recurrent dislocation of
the patellas has been described in association with
triphalangeal thumbs, hand polydactyly, brachydactyly, and camptodactyly, and short stature in a
mother and three daughters (triphalangeal thumbs/
recurrent dislocation of patella, OMIM 190650) (Say
et al. 1976).
Patellar dislocation occurring in the context of
conditions with joint laxity is discussed in Chapter 8.
Radiographic Synopsis
AP, LL, and axial projections. The axial projection,
obtained at 20°, 30°, or 45° of knee flexion, allows visualization of the patellar shape and its relationship
with the femoral trochlea. To assess lateral patellar
displacement an angle is drawn between the anterior
aspect of the femoral condyles and trochlear depth:
the line connecting the median ridge of the patella
and the trochlear depth falls medial to the described
angle in normal conditions (Merchant et al. 1974). To
assess patellar tilt, the angle between the line connecting the anterior aspect of the femoral condyles
and the line traced along the lateral facet of the patella is evaluated. In normal conditions, this angle is
open laterally, while in patients with patellar tilting
either the angle is open medially or the traced lines
run parallel (Laurin et al. 1978). To assess the position of the patella relative to the femoropatellar joint
line, the Insall-Salvati index, which is obtained by
dividing the length of the patellar tendon to the
length of the patella, is measured on the lateral projection (Insall and Salvati 1971). The Insall ratio is
approximately 1 in normal individuals; equal to or
greater than 1.3 in patella alta (high-riding patella);
and equal to or less than 0.7 in patella baja (low-riding patella).
1. Small/absent patellas; iliac horns (nail patella syndrome)
2. Absent patellas; slender long bones; Blount disease; bilateral aseptic necrosis of the lateral femoral
condyles (ear/patella/short stature syndrome)
3. Small patellas; hypoplastic ischia (ischiopatellar
dysplasia)
4. Small/absent patellas; tibial aplasia/hypoplasia;
radial hypoplasia; tibia pseudarthrosis (mesomelic
dysplasia, Werner type and hypoplastic tibia-radius type)
5. Aplastic patellas; tibia hypoplasia (popliteal pterygium syndrome)
6. Small, double-layered patella; patellar instability
(multiple epiphyseal dysplasia)
Abnormalities of the Long Bones in the Lower Extremities
Associations
• Acrocephalosyndactyly (Carpenter syndrome)
• Anonychia-onychodystrophy
• Arthrogryposis multiplex congenita
• Chromosome 8 trisomy
• Chondromalacia of patella
• Contractural arachnodactyly, congenital
(Beals syndrome)
• Diastrophic dysplasia
• Ear, patella, short stature syndrome
(Meier-Gorlin)
• Ehlers-Danlos syndrome, type II
• Familial aplasia-hypoplasia of the patella
• Familial recurrent patellar dislocation
• Ischiopatellar dysplasia
• Joint laxity, familial
• Kuskokwim syndrome
• Larsen syndrome
• Mesomelic dysplasia
(hypoplastic tibia and radius type)
• Mesomelic dysplasia (Werner type)
• Multiple epiphyseal dysplasia
• Nail-patella syndrome
• Neurofibromatosis
• Patellar aplasia-coxa vara-tarsal synostosis
• Patellar hypoplasia
• Pterygium syndrome (popliteal)
• Rubinstein-Taybi syndrome
• Seckel syndrome
• Spondyloepimetaphyseal dysplasia
• Spondyloepiphyseal dysplasia
• Stickler syndrome
• Thrombocytopenia-absent radius syndrome
• Trauma
• Triphalangeal thumbs and dislocation of patella
References
Bensahel H, Souchet P, Pennecot GF, Mazda K. The unstable
patella in children. J Pediatr Orthop B 2000; 9: 265–70
Borochowitz Z, Soudry M, Mendes DG. Familial recurrent
dislocation of patella with autosomal dominant mode of
inheritance. Clin Genet 1988; 33: 1–4
Brattstrom H. Patella alta in non-dislocating knee joints. Acta
Orthop Scand 1970; 41: 578–88
Carter C, Sweetnam R. Recurrent dislocation of the patella and
of the shoulder: their association with familial joint laxity.
J Bone Joint Surg Br 1960; 42: 721–7
Cohen B, Temple IK, Symons JC, Hall CM, Shaw DG, Bhamra
M, Jackson AM, Pembrey ME. Microtia and short stature: a
new syndrome. J Med Genet 1991; 28: 786–90
Dahners LE, Francisco WD, Halleran WJ. Findings at arthrotomy in a case of double layered patellae associated with multiple epiphyseal dysplasia. J Pediatr Orthop 1982; 2: 67–70
329
David-Chausse J, Vignes L. Critical study of patella alta. II.
Patella alta and femoropatellar pathology. Rev Rhum Mal
Osteoartic 1982; 49: 507–13
Eilert RE. Congenital dislocation of the patella. Clin Orthop
2001; 389: 22–9
Escobar V, Weaver D. Popliteal pterygium syndrome: a phenotypic and genetic analysis. J Med Genet 1978; 15: 35–42
Frandsen PA, Kristensen H. Osteochondral fracture associated
with dislocation of the patella: another mechanism of injury. J Trauma 1979; 19: 195–7
Gardner J, Woods D, Williamson D. Management of doublelayered patellae by compression screw fixation. J Pediatr
Orthop B 1999; 8: 39–41
Gorlin RJ, Cervenka J, Moller K, Horrobin M, Witkop CJ Jr. A
selected miscellany. Birth Defects Orig Art Ser 1975; 2:
39–50
Green WT Jr. Painful bipartite patellae. A report of three cases.
Clin Orthop 1975; 110: 197–200
Insall J, Goldberg V, Salvati E. Recurrent dislocation and the
high-riding patella. Clin Orthop 1972; 88: 67–9
Insall JN, Salvati E. Patella position in the normal knee joint.
Radiology 1971; 101: 101–4
Laurin CA, Levesque HP, Dussault R, Labelle H, Peides JP.
The abnormal lateral patellofemoral angle: a diagnostic
roentgenographic sign of recurrent patellar subluxation.
J Bone Joint Surg Am 1978; 60: 55–60
Leroy J. Dominant mesomelic dwarfism of the hypoplastic tibia, radius type. Clin Genet 1975; 7: 280–6
Loeys BL, Lemmerling MM, Van Mol CE, Leroy JG. The MeierGorlin syndrome, or ear-patella-short stature syndrome, in
sibs. Am J Med Genet 1999; 84: 61–7
Mangino M, Sanchez O, Torrente I, De Luca A, Capon F, Novelli G, Dallapiccola B. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21–22.
Am J Hum Genet 1999; 65: 441–7
Merchant AC, Mercer RL, Jacobsen RH, Cool CR. Roentgenographic analysis of patellofemoral congruence. J Bone Joint
Surg Am 1974; 56: 1391–6
Miller GF. Familial recurrent dislocation of the patella. J Bone
Joint Surg Br 1978; 60: 203–4
Pashayan H, Fraser FC, McIntyre JM, Dunbar JS. Bilateral aplasia of the tibia, polydactyly and absent thumbs in father
and daughter. J Bone Joint Surg Br 1971; 53: 495–9
Rubacky GE. Inheritable chondromalacia of the patella. J Bone
Joint Surg Am 1963; 45: 1685–8
Sakai N, Koshino T, Okamoto R. Patella baja after displacement
of tibial tuberosity for patellofemoral disorders. Bull Hosp
Joint Dis 1993; 53: 25–8
Say B, Field E, Coldwell JG, Warnberg L, Atasu M. Polydactyly
with triphalangeal thumbs, brachydactyly, camptodactyly,
congenital dislocation of the patellas, short stature and
borderline intelligence. Birth Defects Orig Art Ser 1976; 5:
279–86
Scott JE, Taor WS. The ‘small patella’ syndrome. J Bone Joint
Surg Br 1979; 61: 172–5
Sheffield EG. Double-layered patella in multiple epiphyseal
dysplasia: a valuable clue in the diagnosis. J Pediatr Orthop
1998; 18: 123–8
Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B,
Spranger J, Kunze J. Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double
layered patella caused by a DTDST mutation. J Med Genet
1999; 36: 621–4
330
Chapter 5 · Long Bones
Van Holsbeeck M,Vandamme B, Marchal G, Martens M,Victor
J, Baert AL. Dorsal defect of the patella: concept of its origin
and relationship with bipartite and multipartite patella.
Skeletal Radiol 1987; 16: 304–11
Williams HJ, Hoyer JR. Radiographic diagnosis of osteo-onychodysostosis in infancy. Radiology 1973; 109: 151–4
Epiphyseal Abnormalities
As already discussed in this chapter, epiphyses undergo ossification by virtue of endochondral bone
formation, which implies an intermediate cartilage
model. The process is initiated by invasion of the cartilage model with vascular channels and proceeds
with deposition of bone matrix, which subsequently
undergoes mineralization. Once the secondary ossification centers are formed, they continue to enlarge
until the entire cartilaginous matrix is ossified, except for a thin marginal layer that persists at the
intervening joint as articular cartilage.
Structural defects of the cartilaginous anlage, or
derangements in the process of cartilage calcification, as outlined above, are responsible for the development of a variety of epiphyseal abnormalities,
some of which are discussed in the following pages.
The mechanism of bone mineralization is complex
and only partly understood (Resnick et al. 1995). The
initial deposition of inorganic calcium and phosphate occurs along the longitudinal axis of the collagen fibril, probably at specific sites resulting from
overlap of contiguous polymers of collagen (Boskey
1982). Thus, appropriateness of the collagen structure is of critical importance in bone mineralization.
Conditions caused by mutations in type II collagen
locus (COL2A1), including most of the spondyloepiphyseal and spondyloepimetaphyseal dysplasias,
achondrogenesis type II (Langer-Saldino), hypochondrogenesis, Stickler syndrome, and Kniest dysplasia, are associated with abnormally structured
cartilage anlage and epiphyseal manifestations (Murray et al. 1989; Byers 1989). Once the process of nucleation, i.e., formation of the smallest stable combination of ions that can persist in solution, is initiated,
further precipitation of calcium and phosphate ions
ensures additional growth of the crystalline unit
(Boskey 1982; Posner 1985). However, there is no uniform consensus on the site of nucleation, and the
ground substance, the proteoglycans, and cellular extrusions of the osteoblasts have all been implicated,
in addition to the collagen fibrils (Bernard 1969).
Moreover, there is evidence that the process of calcification is regulated not only by the specific conditions of the organic matrix (alkaline phosphatase
activity, pH, etc.), but also by cellular products that
either facilitate the process of crystallization or remove inhibitors that compete with calcium and
phosphate for sites of initial nucleation or subsequent growth (Boskey 1982). As a consequence,
unavailability of substrates, changes in the conditions of the milieu, or cellular dysfunction, may all
lead to disruption of the orderly coherent process of
mineralization with formation of altered bone.
References
Bernard GW. The ultrastructural interface of bone crystals and
organic matrix in woven and lamellar endochondral bone.
J Dent Res 1969; 48: 781–8
Boskey AL. Current concepts of the physiology and biochemistry of calcification. Clin Orthop 1981; 157: 225–57
Posner AS. The mineral of bone. Clin Orthop 1985; 200: 87–99
Murray LW, Bautista J, James PL, Rimoin DL. Type II collagen
defects in the chondrodysplasias. I. Spondyloepiphyseal
dysplasias. Am J Hum Genet 1989; 45: 5–15
Byers PH. Molecular heterogeneity in chondrodysplasias. Am J
Hum Genet 1989; 45: 1–4
Resnick D, Manolagas SC, Niwayama G, Fallon MD. Histogenesis, anatomy, and physiology of bone. In: Resnick D (ed.)
Diagnosis of bone and joint disorders.W. B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 609–51
Stippled Epiphyses
䉴 [Dense, punctate pattern
of epiphyseal calcification]
This aberrant pattern of epiphyseal calcification,
which is clearly different from the epiphyseal irregularities that represent normal developmental variations (Swischuk and John 1995), occurs most typically in chondrodysplasia punctata. Patterns vary
among different types to some extent (Theander and
Pettersson 1978). In chondrodysplasia punctata, rhizomelic type (OMIM 215100), punctate calcifications
occur primarily in the hips and shoulders, while they
are absent in the axial skeleton (Mason and Kozlowski 1973) (Fig. 5.36). The distribution is strikingly
symmetrical. Children surviving beyond infancy
show gradual disappearance of the stippling, most
commonly within the first 2 years (Wardinsky et al.
1990). Once stippling has dissolved, it is replaced
most commonly by permanent epiphyseal abnormalities. The severity of this late sequel seems to correlate with the degree of early stippling (Lawrence
et al. 1989). In chondrodysplasia punctata; ConradiHünermann (OMIM 118650, 302960), punctate
Epiphyseal Abnormalities
331
Fig. 5.36. Chondrodysplasia
punctata, rhizomelic type in a
newborn. Note punctate stippling around the shoulder and
elbow, and severe humeral
shortening
Fig. 5.37 a, b. Chondrodysplasia punctata, Conradi-Hunermann. a Observe punctate calcifications in the knee and hip
epiphyses, and around the
pelvis. b Multiple punctate foci of calcification are also evident in the carpal bones.
There is also postaxial polydactyly. (From Poznanski
1994)
a
calcifications primarily affect the ends of the
long and short tubular bones, end-plates and
processes of the vertebrae, carpal and tarsal bones,
ischiopubic bones, and cartilaginous structures
of the trachea and pharynx (Silengo et al. 1980)
(Fig. 5.37a,b). The calcifications are most often asymmetrical, as is limb shortening. Epiphyseal ossification is less severely delayed and distorted in ConradiHünermann disease than in the rhizomelic type. The
pathologic substrate of punctate calcifications is mucoid degeneration with cyst formation of the cartilaginous matrix in the epiphyseal centers. Calcification of the cysts and surrounding cartilage leads to
the stippled appearance. The primary fault in the
development of the cartilaginous matrix remains
unknown, however (Rasmussen and Reimann 1973).
Stippling has also been described in association
with chromosomal anomalies, GM1 gangliosidosis, and drug-induced embryopathies, including
warfarin embryopathy and phenytoin syndrome
(Leicher-Duber et al. 1990). Maternal ingestion of
vitamin K antagonist anticoagulants in early pregnancy may give rise to warfarin embryopathy. In
addition to the hemorrhagic complications, clinical
and radiographic characteristics of the disease include craniofacial dymorphism, with collapsed nasal
bridge, short neck, short limbs, brachydactyly, respiratory discomfort, and widespread stippled calcifica-
b
tions in both the appendicular and the axial skeleton
(Hall et al. 1980). After reviewing the published cases
of pregnancies in which coumarin derivatives (418
cases) or heparin (135 cases) were administered, Hall
et al. concluded that use of either class of anticoagulant carried substantial risks (approximately one
third of pregnancies culminating in abortion, stillbirth, or live births of abnormal infants and two
thirds in live births of apparently normal infants with
the use of either drug) (Hall et al. 1980). A phenotype
identical to that of warfarin embryopathy has been
reported in a boy with an inborn deficiency of vitamin K epoxide reductase, suggesting that coumarin
derivatives may interfere with carboxylation of various vitamin K-dependent bone proteins (Pauli et al.
1987). Zellweger syndrome (cerebro-hepato-renal
syndrome, OMIM 214100) is a lethal autosomal recessive disease characterized by craniofacial dysmorphism, brain dysgenesis, seizures, profound muscular hypotonia, renal cortical cysts, cirrhosis, and soft
tissue calcifications, especially around the patellas
and the hips, resembling the stippled calcifications of
chondrodysplasia punctata (Poznanski et al. 1970)
(Fig. 5.38a,b). Punctate calcifications primarily involving the patella should lead to consideration of Zellweger syndrome in the diagnostic workup. The biochemical defects underlying this disorder, some of
which are the same as those occurring in the rhi-
332
Chapter 5 · Long Bones
a
b
Fig. 5.38 a, b. Zellweger syndrome in a newborn. a There are
multiple punctate calcification foci in the patella, but not in the
knee epiphyses. b Punctate calcifications are also visible in the
hips and the pelvic region. (From Poznanski 1994)
zomelic form of chondrodysplasia punctata, include
absence of peroxisomes in liver and kidney cells; deficiency of the enzyme DHAPAT (dihydroxyacetone
phosphate acetyltransferase); deficiency of plasmalogen in the liver, kidney, brain, muscle, and heart;
and accumulation of very-long-chain fatty acids
(Zellweger 1987). Following the fortuitous discovery
of a peroxisomal dysfunction in a girl with congenital rubella and epiphyseal stippling, a recommendation was given that any child with epiphyseal stippling should be assessed for peroxisomal disease
(Pike et al. 1990). An apparently ‘new’ association of
lissencephaly type III (agyric brain with hypoplastic
brain stem and cerebellum, severe neuronal loss of
the cortical plate, matrix zone, basal ganglia, brain
stem nuclei, and spinal cord with axonal swelling and
microcalcification), short metacarpals and phalanges, and epiphyseal stippling of cervical vertebrae,
feet, and sacrum has been described in sibs born to
consanguineous parents (Plauchu et al. 2001).
3. Stippled calcifications in the appendicular and
axial skeleton (warfarin embryopathy)
4. Stippled calcifications of the hips and patellas
(Zellweger syndrome)
Radiographic Synopsis
1. Punctate calcifications in the proximal humerus
and femur, with symmetrical distribution; absent
stippling in the axial skeleton; severe epiphyseal
changes after stippling resolution (chondrodysplasia punctata, rhizomelic type)
2. Punctate calcifications at the ends of the long
bones, processes of vertebrae, carpal and tarsal
bones, and ischiopubic bones; asymmetrical distribution; less severe epiphyseal changes after
stippling resolution (chondrodysplasia punctata,
Conradi-Hünermann)
Associations
• Acrodysostosis
• Astley-Kendall syndrome
• Cerebro-costo-mandibular syndrome
• CHILD syndrome
• Chondrodysplasia punctata
• Chromosomal abnormalities (trisomy 18, 21)
• Fetal alcohol syndrome
• GMI gangliosidosis
• Hypothyroidism
• Infection (prenatal rubella, listeria)
• Niemann-Pick disease
• Phenytoin syndrome
• Smith-Lemli-Opitz syndrome
• Spondylometa-epiphyseal dysplasia/short limb/
abnormal calcification type
• Warfarin embryopathy
• Zellweger syndrome
References
Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of
anticoagulation during pregnancy. Am J Med 1980; 68:
122–40
Lawrence JJ, Schlesinger AE, Kozlowski K, Poznanski AK,
Bacha L, Dreyer GL, Barylak A, Sillence DO, Rager K. Unusual radiographic manifestations of chondrodysplasia
punctata. Skeletal Radiol 1989; 18: 15–9
Epiphyseal Abnormalities
Leicher-Duber A, Schumacher R, Spranger J. Symptomatic calcification in the newborn. Phenocopies of chondrodysplasia punctata. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb
Verfahr 1990; 152: 463–8
Mason RC, Kozlowski K. Chondrodysplasia punctata. A report
of 10 cases. Radiology 1973; 109: 145–50
Pauli RM, Lian JB, Mosher DF, Suttie JW. Association of congenital deficiency of multiple vitamin K-dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of
coumarin derivatives. Am J Hum Genet 1987; 41: 566–83
Pike MG, Applegarth DA, Dunn HG, Bamforth SJ, Tingle AJ,
Wood BJ, Dimmick JE, Harris H, Chantler JK, Hall JG. Congenital rubella syndrome associated with calcific epiphyseal stippling and peroxisomal dysfunction. J Pediatr 1990;
116: 88–94
Plauchu H, Encha-Razavi F, Hermier M, Attia-Sobol J,Vitrey D,
Verloes A. Lissencephaly type III, stippled epiphyses and
loose, thick skin: a new recessively inherited syndrome. Am
J Med Genet 2001; 99: 14–20
Poznanski A. Punctate epiphyses: a radiological sign not a disease. Pediatr Radiol 1994; 24: 418–24
Poznanski AK, Nosanchuk JS, Baublis J, Holt JF. The cerebrohepato-renal syndrome (CHRS) (Zellweger’s syndrome).
Am J Roentgenol Radium Ther Nucl Med 1970; 109: 313–22
Rasmussen PG, Reimann I. Multiple epiphyseal dysplasia with
special reference to histologic findings. Acta Pathol Microbiol Scand 1973; 81: 381–9
Silengo MC, Luzzatti L, Silverman FN. Clinical and genetic
aspects of Conradi-Hunermann disease. A report of three
familial cases and review of the literature. J Pediatr 1980;
97: 911–7
Swischuk LE, John SD. Differential diagnosis in pediatric radiology. Williams & Wilkins, Baltimore, 1995, p. 200
Theander G, Pettersson H. Calcification in chondrodysplasia
punctata. Relation to ossification and skeletal growth. Acta
Radiol Diagn 1978; 19: 205–22
Wardinsky TD, Pagon RA, Powell BR, McGillivray B, Stephan
M, Zonana J, Moser A. Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature
and five case reports. Clin Genet 1990; 38: 84–93
Zellweger H. The cerebro-hepato-renal (Zellweger) syndrome
and other peroxisomal disorders. Dev Med Child Neurol
1987; 29: 821–9
Hypoplastic, Dysplastic, Dysgenetic Epiphyses
䉴 [Small, irregular/fragmented,
late-appearing epiphyses]
Since epiphyseal ossification parallels the growth and
maturation of the remainder of the skeleton, epiphyseal hypoplasia can merely reflect a delay in skeletal
maturation. The topic of delayed skeletal age and
methods of estimation is discussed in Chapter 9.
Asymmetry in the epiphyseal size can be a normal
finding, especially in rapidly growing children. However, a single underdeveloped epiphysis may also
suggest defective growth caused by trauma or infec-
333
tion. Generalized epiphyseal hypoplasia usually reflects a systemic disorder involving the epiphyses. In
these cases, in addition to being small, the epiphyses
are often irregular and fragmented. On the other
hand, irregularity deriving from multicenter ossification can be a developmental variant in otherwise
normal children. These variants are frequent at the
distal femoral epiphysis, while location at the capitellum and femoral head is less common. Both hypoplasia of the capitellum and radial head and hypoplasia
of the lateral portions of the distal femoral epiphyses
occur in nail-patella syndrome (OMIM 256020). The
term ‘fragmentation’ refers to a previously normally
formed epiphysis and its subsequent alteration by
intervening factors. However, differentiation between
a fragmented epiphysis and an epiphysis that is irregular because of an inherent growth defect is not always reliable, either radiographically or pathologically. The occurrence of epiphyseal changes on the
borderline between normality and pathology, together with the notion that minor epiphyseal changes occur in almost every skeletal dysplasia, malformation
syndrome or metabolic disorder, makes subtle
epiphyseal abnormalities meaningless in the diagnostic process (Kozlowski and Beighton, 1995).
Late appearance of the ossification centers with
consequent smallness of epiphyses for age is a
striking feature in children with untreated hypothyroidism, a condition characterized by severely
delayed bone maturation. Moreover, ossification
from multiple centers is common, leading to irregular or fragmented epiphyses. These ‘dysgenetic’ epiphyses are located especially at the femoral and
humeral heads (Parker 1981). Other skeletal manifestations of infantile hypothyroidism include generalized osteoporosis, wormian bones, soft tissue calcification, and vertebral and rib anomalies (Bamforth et
al. 1986). The primary defect in the disorders grouped
under the general designation of ‘epiphyseal dysplasias’ consists in the formation of an abnormal cartilaginous anlage, which results in turn in abnormal
development of the secondary ossification centers.
Epiphyseal ossification is delayed, and formed epiphyses are irregular, fragmented, and flattened
(Shapiro 1987). Cartilage abnormalities include a decreased number of chondrocytes, loss of columnar
arrangement of chondrocytes, excess of matrix, and
areas of matrix degeneration. As anticipated, these
abnormalities are related to mutations in the type II
collagen locus (COL2A1). Interestingly, conditions
associated with mutations in the gene encoding for
the type II collagen, such as spondyloepiphyseal dysplasia congenita (OMIM 183900), show a clinical pic-
334
Chapter 5 · Long Bones
a
c
b
d
e
Fig. 5.39 a–e. Multiple epiphyseal dysplasia. a In a 12-year-old
girl with COMP mutation (same case as in Fig. 4.35a) the epiphyses are only mildly flattened, but their contour is grossly
regular. b In a 16-year-old male youth with COMP mutation
the epiphyses show more severe changes than are seen in a,
with flattening, irregular contours, and dysplastic appearance.
c The radiograph of a 6-year-old patient with pseudoachondroplasia, also due to mutation in the COMP gene, is shown for
comparison. Note marked smallness of the epiphyses at the
knee, and severe metaphyseal abnormalities, with flaring, irregularities, and marginal ossification defects. d In a 13-yearold boy with COL9A3 mutation the distal femoral and proximal tibial epiphyses are small and dysplastic in appearance,
with strikingly irregular contour. e In a 14 1/2-year-old boy
with COL9A2 mutation, again, severe epiphyseal abnormalities
are evident about the knee. (From Unger et al. 2001)
ture (epiphyseal changes, platyspondyly, kyphoscoliosis, and ocular abnormalities) that grossly corresponds to the anatomical location of type II collagen,
a component of the hyaline cartilage, nucleus pulposus, and vitreous of the eye (Anderson et al. 1990).
The conditions characterized by irregular epiphyses
are predisposed to the development of joint incongruity and early degenerative joint changes. Multiple
epiphyseal dysplasia (OMIM 132400) is the prototype
of such conditions (Treble et al. 1990). As discussed
elsewhere in the book, multiple epiphyseal dysplasia
is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three
genes: the COL9A2 (OMIM 600204) and COL9A3
(OMIM 600969) genes of type IX procollagen and
the cartilage oligomeric matrix protein COMP gene
(OMIM 600310) allelic to pseudoachondroplasia.
The pattern of joint involvement may vary according
to the genotype. Patients with COL9A2 and COL9A3
mutations display severe joint involvement at the
knees and relative hip sparing. By contrast, patients with COMP mutation show significant involvement of the femoral capital epiphyses and acetabuli and varying degrees of knee involvement
(Unger et al. 2001) (Fig. 5.39a–e). In the autosomal dominant Kniest dysplasia (OMIM 156550),
Epiphyseal Abnormalities
335
a
Fig. 5.40. Dyggve-Melchior-Clausen dysplasia in a 14-monthold child (same case as in Fig. 3.5). The epiphyses are small and
irregularly ossified. Metaphyseal ossification is also defective.
(Courtesy of Dr. S. Fasanelli, Ospedale Bambino Gesù, Rome,
Italy)
epiphyseal development is irregular and delayed, especially in the proximal femurs. The epiphyses, including those in the hands and feet, are fragmented,
flattened, and poorly formed. Those in the knees may
become larger than normal, and the growth plate of
the proximal tibia may have an inverted V-shaped
configuration. Additional manifestations include a
flattened face with depressed nasal bridge, cleft
palate, deafness, short trunk, prominent stiff joints,
short tubular bones, metaphyseal widening, clubfeet,
and spinal kyphoscoliosis (Lachman et al. 1975). In
Dyggve-Melchior-Clausen dysplasia (OMIM 223800)
epiphyseal ossification is delayed and irregular. The
metaphyses are also irregularly ossified. The proximal femurs have horizontal, undulating growth
plates and hypoplastic epiphyses (Fig. 5.40). A peculiar type of epiphyseal hypoplasia in the distal tibia,
with relative hypoplasia of the outer portion resulting in downward slanting of the talar dome, may be
found in patients with Stickler syndrome (arthroophthalmopathy, OMIM 108300). However, (mild)
epiphyseal dysplasia is widespread. As in multiple
b
Fig. 5.41 a, b. Parastremmatic dwarfism in a 13-year-old girl.
Note grossly irregular bone structure at the ends of the long
bones, with ‘flocky’ or ‘woolly’ ossification extending to both
sides of the physeal line. The epiphyses are flattened. The
coarse bone trabeculation with areas of dense stippling also
involves the glenoid cavity of the scapula
epiphyseal dysplasia, joint degenerative arthropathy
occurs prematurely in this disorder, with formation
of cysts and dense inclusions in the subarticular
bone. The clinical picture of Stickler syndrome includes a marfanoid habitus, eye problems, cleft
palate, micrognathia, and swollen joints (Opitz et al.
1972). Another special type of epiphyseal hypoplasia
is seen in chondroectodermal dysplasia (Ellis-van
Creveld syndrome, OMIM 225500). In this condition,
hypoplasia predominantly involves the proximal epiphyses of both tibias, the lateral portions being most
336
Chapter 5 · Long Bones
markedly affected (Caffey 1952). Strikingly irregular
ossification of the epiphyses and metaphyses occurs
in parastremmatic dwarfism (OMIM 168400), a severely dwarfing condition with kyphoscoliosis, contractures of major joints, and progressive skeletal deformities (twisted dwarfism) (Fig. 5.41a,b). Whether
Meyer dysplasia is a localized form of epiphyseal dysplasia or just a normal variant of ossification is not
known (Meyer 1964). The pathological hallmark of
the disease is the irregular and flattened appearance
of both femoral heads. Ossification of the femoral
capital epiphyses is delayed, beginning at around
2 years of age instead of 5–6 months, and proceeds
from multiple, granular foci that coalesce over time
(by approximately 5 years). The final result is formation of completely normal femoral heads (Harrison
1971). Hence, Meyer dysplasia is a self-limiting condition, whose benign clinical course has precluded understanding of the underlying pathogenetic
mechanism. Unlike the picture in Legg-Calvè-Perthes
disease (OMIM 150600), an osteonecrotic process of
the femoral head, epiphyseal changes in Meyer dysplasia have a bilateral distribution, are not associated
with variations of the vascular supply as detected by
radionuclide studies, and do not result in permanent
epiphyseal abnormalities, such as bone sclerosis and
flattening.
Radiographic Synopsis
AP, LL and oblique projections (depending on the
anatomical site being investigated)
1. Hypoplasia of capitellum and radial head; hypoplasia of the lateral aspect of distal humerus; increased carrying angle of elbow; hypoplastic/
absent patellas; hypoplasia of the lateral portions
of the distal femoral epiphyses (nail-patella syndrome)
2. In infancy, delayed bone age; cortical thickening
of the tubular bones, with moderate bone sclerosis; in childhood, retarded and irregular epiphyseal ossification (epiphyseal dysgenesis); irregular mineralization of metaphyses (hypothyroidism)
3. In infancy, delayed bone age with absent ossification of the knee epiphyses and pubic bones;
in childhood, severely retarded ossification of
femoral heads and necks; varying degrees of epiphyseal and metaphyseal abnormalities (spondyloepiphyseal dysplasia congenita)
4. Irregular epiphyses (flat in Ribbing type, small in
Fairbank type); mild shortening of tubular bones;
normal metaphyses; early, progressive osteoarthritis (multiple epiphyseal dysplasia)
5. Irregular, late-appearing proximal femoral epiphyses; in childhood, large and deformed epiphyses; short and broad femoral necks; broad metaphyses; short tubular bones (Kniest dysplasia)
6. In childhood, mild epiphyseal dysplasia most
prominent at proximal femurs and distal tibias;
asymmetrical hypoplasia of distal tibial epiphysis
with external slanting of the talar dome; in adulthood, secondary degenerative arthropathy (Stickler syndrome)
7. Deficient ossification of the lateral portions of
proximal tibial epiphysis and metaphysis; downward slanting of the lateral end of proximal tibias;
knock-knee deformity (chondroectodermal dysplasia)
8. Coarse trabecular pattern (‘flocky’ ossification) of
the bone structure of metaphyses and epiphyses;
severe epiphyseal deformation (parastremmatic
dwarfism)
9. Late-appearing, small, irregular femoral heads;
mild irregularities of proximal femoral metaphyses; spontaneous resolution of the abnormalities,
with formation of normal femoral heads (Meyer
dysplasia)
Associations
• Avascular necrosis
• Chondroectodermal dysplasia (Ellis-van Creveld)
• Deaf mutism–goiter–euthyroidism syndrome
• DeBarsy syndrome
(cutis laxa–corneal clouding–mental retardation)
• Diastrophic dysplasia
• Dyggve-Melchior-Clausen syndrome
• Dysplasia epiphysealis hemimelica
• Homocystinuria
• Hypopituitarism
• Hypothyroidism
• Infection
• Inflammation
• Kniest dysplasia
• Legg-Calvè-Perthes disease
• Metatropic dysplasia
• Meyer dysplasia
• Mucopolysaccharidosis
• Multiple epiphyseal dysplasia
• Multiple epiphyseal dysplasia
with early-onset diabetes mellitus
• Nail-patella syndrome
• Neurological or neuromuscular diseases
• Opsismodysplasia
• Osteochondroses
• Osteopathia striata
• Osteopetrosis
Epiphyseal Abnormalities
•
•
•
•
•
•
•
•
•
•
•
•
•
•
337
Osteopoikilosis
Parastremmatic dwarfism
Pseudoachondroplasia
Pseudodiastrophic dysplasia
Rheumatoid arthritis
Smith-McCort syndrome
Spondyloepimetaphyseal dysplasia
Spondyloepiphyseal dysplasia congenita
Spondyloepiphyseal dysplasia tarda
Stickler syndrome
Tricho-rhino-phalangeal syndromes I and II
Weaver syndrome
Winchester syndrome
Wolcott-Rallison syndrome
References
Anderson IJ, Goldberg RB, Marion RW, Upholt WB, Tsipouras
P. Spondyloepiphyseal dysplasia congenita: genetic linkage
to type II collagen (COL2AI). Am J Hum Genet 1990; 46:
896–901
Bamforth JS, Hughes I, Lazarus J, John R. Congenital anomalies associated with hypothyroidism. Arch Dis Child 1986;
61: 608–9
Caffey J. Chondroectodermal dysplasia (Ellis-van Creveld syndrome): report of three cases. AJR Am J Roentgenol 1952;
68: 875–81
Harrison CS. Dysplasia epiphysealis capitis femoris. Clin
Orthop 1971; 80: 118–25
Kozlowski K, Beighton P. Gamut index of skeletal dysplasias:
an aid to radiodiagnosis. Springer, New York Berlin Heidelberg 1995 (2nd ed.), p. 67
Lachman RS, Rimoin DL, Hollister DW, Dorset JP, Siggers DC,
McAlister W, Kaufman RL, Langer LO. The Kniest syndrome. Radiology 1975; 123: 805–9
Meyer J. Dysplasia epiphysealis capitis femoris. A clinico-radiological syndrome and its relationship to Legg-CalvèPerthes disease. Acta Orthop Scand 1964; 34: 183–97
Opitz JM, Franc T, Herrmann J. The Stickler syndrome. N Engl
J Med 1972; 286: 546–7
Parker BR. Hypothyroidism with epiphyseal dysgenesis. Pediatric case of the day. AJR Am J Roentgenol 1981; 136: 1030
Shapiro F. Epiphyseal disorders. N Engl J Med 1987; 317:
1702–10
Treble NJ, Jensen FO, Bankier A, Rogers JG, Cole WG. Development of the hip in multiple epiphyseal dysplasia. Natural
history and susceptibility to premature osteoarthritis.
J Bone Joint Surg Br 1990; 72: 1061–4
Unger SL, Briggs MD, Holden P, Zabel B, Ala-Kokko L, Paassilta P, Lohiniva J, Rimoin DL, Lachman RS, Cohn DH. Multiple epiphyseal dysplasia: radiographic abnormalities correlated with genotype. Pediatr Radiol 2001; 31: 10–8
Fig. 5.42. Dysplasia epiphysealis hemimelica (Trevor disease) in
a 14-year-old boy. Observe overgrowth of the medial femoral
condyle, resulting in valgus deformity of the knee. There are
prominent calcifications of the lateral femoral condyle, lateral
tibial epiphysis, and fibular epiphysis. (From Merzoug et al. 2002)
Large Epiphyses
䉴 [Epiphyses of increased size]
Large epiphyses can be confined to a specific
anatomic site or occur on a generalized basis.
Localized cartilaginous overgrowth of one or more
epiphyses is seen in dysplasia epiphysealis hemimelica
(Trevor disease, OMIM 127800), a disorder of unknown inheritance, affecting boys about three times
as frequently as girls in the age range of 2–14 years
(Trevor 1950). Histologically, the lesion is undistinguishable from an ordinary osteochondroma (Lang
and Azouz 1997). The epiphyseal involvement is typically hemimelic, meaning that either the medial
(more typically) or the lateral side of the epiphysis
shows focal cartilaginous overgrowth (Fig. 5.42). Frequent anatomical locations include the lower limbs,
notably the epiphyses of the knee and the carpal and
tarsal bones (Silverman 1989). Patients with involvement of both legs and/or arms have been reported
(Wiedemann et al. 1981; Merzoug et al. 2002). Clinical
manifestations include swelling and tenderness, often
painless, usually localized to the knee and/or ankle on
one side of the body only (Wolfgang and Heath 1976).
Premature epiphyseal fusion, resulting in limb-length
discrepancy, limb misalignment, notably genu valgum, and precocious osteoarthritis are frequent se-
338
Chapter 5 · Long Bones
Fig. 5.43. Oto-spondylomegaepiphyseal dysplasia (recessive
OSMED) in a 4-year-old child. The capital femoral epiphyses
are large; the femoral necks are wide and in valgus position.
(From Spranger 1998)
quelae. Marked enlargement of the epiphyses with an
irregular pattern of ossification occurs on a generalized basis in infantile multisystem inflammatory disease. Clinical symptoms are present at birth or become apparent in early infancy, and consist in febrile
arthritis associated with an evanescent rush, lymphadenopathy, leukocytosis, anemia, elevated sedimentation rate, chronic meningitis, cerebrospinal fluid pleocytosis, papilledema, unusual uveitis, and increased serum IgG levels. Radiologic manifestations
include diffuse osteoporosis, swollen joints, periosteal
reaction around the shafts of the long bones, metaphyseal widening, and large, irregular, and fragmented epiphyses. The epiphyses at the distal end of the femurs may become cone shaped in later stages, with
notching of the corresponding metaphysis. The findings are distinctive and allow a specific diagnosis
(Yarom et al. 1985; Kaufman and Lovell 1986). Together with metaphyseal irregularities and defective vertebral body ossification, megaepiphyses are also the
hallmark of the rare autosomal recessive spondylomegaepiphyseal-metaphyseal dysplasia (SilvermanReiley, OMIM 249230) (Silverman and Reiley 1985).
Additional features include delayed carpal bone
ossification, pseudoepiphyses in the hands and feet,
hypoplastic iliac wings, coxa valga, unossified pubic
bones, and hypoplasia of the facial bones. Another
condition with megaepiphyses, most prominent at
the level of the knee and hip, is oto-spondylo-megaepi-
physeal dysplasia (OSMED, OMIM 215150), an allencompassing designation for the non-ocular forms
of Stickler syndrome (Stickler type III, OMIM
184840) (Fig. 5.43). The term refers to the association
of sensorineural deafness, a characteristic facies
(midfacial hypoplasia, short upturned nose, depressed nasal bridge, prominent eyes, and supraorbital ridges), cleft palate, short stature, platyspondyly, progressive carpal synostosis, prominent
interphalangeal joints, and subcutaneous calcifications (Insley and Astley 1974). Linkage studies have
mapped the disease gene to 6p21.3. Both the heterozygous form of OSMED (Weissenbacher-Zweymuller
syndrome, OMIM 277610) and the homozygous form
of OSMED (Insley-Astley syndrome, OMIM 215150)
are caused by mutation in the COL11A2 gene (Kelly
et al. 1982; Pihlajamaa et al. 1998). Some other very
rare conditions are associated with megaepiphyses.
Macroepiphyses with osteoporosis, prominent and
lax joints, short stature, aged appearance, and
markedly wrinkled palms, have been described in
the autosomal recessive condition of osteoporosismacroepiphyseal dysplasia (OMIM 248010) (McAlister et al. 1986).A case of autosomal recessive megaepiphyseal dwarfism (OMIM 249230) has been described
in a 9-year-old boy born of an incestuous fatherdaughter relationship. Clinical and radiographic findings includes a characteristic facies, cleft palate,
prominent joints with enlarged epiphyses, and subluxation of both lenses (Gorlin et al. 1973).
Radiographic Synopsis
AP and LL projections. Standard norms are available
for the thickness of the distal femoral epiphysis
(Schlesinger et al. 1986). Enlargement of the epiphysis can be assessed by comparison with the companion metaphysis. Simple inspection is adequate in
most cases.
1. Multiple small foci of ossification adjacent to the
medial or lateral aspect of the affected epiphysis;
coalescence with the epiphysis to form an irregular, lobulated bone mass; limb misalignment; precocious osteoarthritis (dysplasia epiphysealis
hemimelica)
2. Epiphyseal enlargement, irregularities, and fragmentation; metaphyseal widening; periostitis; osteoporosis (infantile multisystem inflammatory
disease)
Epiphyseal Abnormalities
3. Large epiphyses; metaphyseal irregularities; defective vertebral body ossification (spondylo-megaepiphyseal-metaphyseal dysplasia)
Associations
• Adrenal hyperplasia
• ASPED (angel-shaped phalango-epiphyseal
dysplasia)
• Beckwith-Wiedemann syndrome
• Chondrodysplasia punctata, Sheffield type
(hands and feet)
• Chronic arthritis
• Cleidocranial dysplasia
• Dysplasia epiphysealis hemimelica
(Trevor disease)
• Fracture (healing) or increased size from overuse
• Goldblatt syndrome
• Hemophilia (hemarthrosis)
• Hyperthyroidism
• Infantile multisystem inflammatory disease
• Kniest dysplasia (hands)
and Kniest-like conditions
• Megaepiphyseal dwarfism
• Megaepiphyseal dysplasia/osteoporosis/wrinkled
skin/aged appearance (McAlister)
• Megaepiphyseal dysplasia/somatic and mental retardation/deafness/enlarged joints/short tubular
bones/extremely large epiphyses (Gorlin)
• Mesomelic dysplasia (Langer)
• Metaphyseal chondrodysplasia (Schmid, Jansen)
• Microcephalic osteodysplastic dysplasia
• Microspherophakia/metaphyseal dysplasia
(Verloes)
• Osteoporosis-macroepiphyseal dysplasia
• Oto-spondylo-megaepiphyseal dysplasia
(OSMED)
• Spondyloepiphyseal dysplasia
with macroepiphyses
• Spondylomegaepiphyseal-metaphyseal dysplasia
(Silverman-Reiley)
References
Gorlin RJ, Alper R, Langer LO Jr. Megaepiphyseal dwarfism.
J Pediatr 1973; 83: 633–5
Insley J, Astley R. A bone dysplasia with deafness. Br J Radiol
1974; 47: 244–51
Kaufman RA, Lovell DJ. Infantile-onset multisystem inflammatory disease: radiologic findings. Radiology 1986; 160:
741–6
Kelly TE, Wells HH, Tuck KB. The Weissenbacher-Zweymuller
syndrome: possible neonatal expression of the Stickler syndrome. Am J Med Genet 1982; 11: 113–9
339
Lang IM, Azouz EM. MRI appearances of dysplasia epiphysealis hemimelica of the knee. Skeletal Radiol 1997; 26:
226–9
McAlister WH, Coe JD, Whyte MP. Macroepiphyseal dysplasia
with symptomatic osteoporosis, wrinkled skin, and aged
appearance: a presumed autosomal recessive condition.
Skeletal Radiol 1986; 15: 47–51
Merzoug V, Wicard P, Dubousset J, Kalifa G. Bilateral dysplasia
epiphysealis hemimelica: report of two cases. Pediatr Radiol 2002; 32: 431–4
Pihlajamaa T, Prockop DJ, Faber J, Winterpacht A, Zabel B,
Giedion A, Wiesbauer P, Spranger J, Ala-Kokko L. Heterozygous glycine substitution in the COL11A2 gene in the original patient with the Weissenbacher-Zweymuller syndrome
demonstrates its identity with heterozygous OSMED
(nonocular Stickler syndrome). Am J Med Genet 1998; 80:
115–20
Schlesinger AE, Poznanski AK, Pudlowski RM, Millar EA. Distal femoral epiphysis: normal standards for thickness
and application to bone dysplasias. Radiology 1986; 159:
515–9.
Silverman FN. Dysplasia epiphysealis hemimelica. Semin
Roentgenol 1989; 24: 246–58
Silverman FN, Reiley MA. Spondylo-megaepiphyseal-metaphyseal dysplasia. Radiology 1985; 156: 365–71
Spranger J. The type XI collagenopathies. Pediatr Radiol 1998;
28: 745–50
Trevor D. Tarso-epiphysial aclasis: a congenital error of epiphysial development. J Bone Joint Surg Br 1950; 32: 204–13
Wiedemann HR, Mann M, von Kreudenstein PS. Dysplasia epiphysealis hemimelica – Trevor disease: severe manifestations in a child. Eur J Pediatr 1981; 136: 311–6
Wolfgang GL, Heath RD. Dysplasia epiphysealis hemimelica. A
case report. Clin Orthop 1976; 116: 32–4
Yarom A, Rennebohm RM, Levinson JE. Infantile multisystem
inflammatory disease: a specific syndrome? J Pediatr 1985;
106: 390–6
Aseptic Necrosis
䉴 [Ischemic necrosis involving the epiphysis
or the subarticular area]
By convention, the term ‘ischemic necrosis’ is used to
describe bone infarction involving the epiphysis or
areas of subarticular location, whereas the term
‘bone infarct’ is applied to areas of metaphyseal and
diaphyseal involvement. Many other designations are
currently used for aseptic necrosis, including avascular necrosis, osteonecrosis, and several eponyms,
each of which is applied to a specific anatomical site.
It is now generally accepted that the term ‘osteochondrosis,’ loosely applied to a heterogeneous group of
unrelated disorders that share certain features
(predilection for the immature skeleton; involvement
of an epiphysis or apophysis; radiographic evidence of bony fragmentation, collapse, and sclerosis)
is misleading and its use should be discouraged
340
Chapter 5 · Long Bones
(Resnick 1995). In fact, this designation includes
primary osteonecrotic processes (e.g., Legg-CalvèPerthes disease and Köhler disease), disorders in
which ischemic necrosis occurs as a secondary event
after a trauma (e.g., Kienböck disease of the lunate
bone), and disorders in which ischemic necrosis is
entirely lacking (e.g., Blount tibia vara, OsgoodSchlatter disease, and Scheuermann disease). In osteonecrosis, ischemia results from interruption of the
blood flow supplying a specific epiphyseal territory.
Vascular supply can be interrupted by vascular obstruction, whether intrinsic or extrinsic, or by physical disruption of the vessel. Since epiphyseal vascularization is limited, most of the epiphyseal surface
being covered by the articular cartilage, which receives the bulk of its nourishment from the synovial
fluid, compromise of a dominant artery supplying
the epiphysis or an ossification center is likely to result in ischemic necrosis.Vulnerability of the epiphyses to vascular insults is further exacerbated in the
growing skeleton by the fact that little or no collateral circulation exists between the epiphysis and adjacent metaphysis, so that most, if not all, of the epiphyseal territory is dependent on the blood supply from
a single vessel (Trueta 1957).. Symptoms are related
to the anatomical location at which osteonecrosis
takes place. Common complaints of osteonecrosis involving the bones around a joint include pain and
limited range of movement in the joint. A limp can be
the presenting symptom in patients with aseptic
necrosis of the femoral head. Late complications of
ischemic necrosis include articular buckling or collapse, loss of articular congruity, and superimposed
degenerative osteoarthritis.
Aseptic necrosis can be idiopathic or occur on a
secondary basis (Pavelka 2000). The label ‘idiopathic’
(or primary, or spontaneous) refers to an osteonecrotic process for which no recognizable causes
are identified. For a sizable group of young patients
with idiopathic osteonecrosis a hereditary basis is
recognized, as discussed later in this section. Some
instances of adult idiopathic osteonecrosis, albeit a
lower proportion, have also been established in
which familial occurrence over several generations
suggests a hereditary predisposition (Arlet 1992).
Common sites of spontaneous osteonecrosis in
adults are the femoral head and femoral condyles.
Primary necrosis of the femoral head affects men
more often than women in the age range of 40–
70 years. Unilateral or bilateral involvement is possible. Spontaneous osteonecrosis about the knee usually affects individuals over 60 years, women more
commonly than men, and has an abrupt onset with
Fig. 5.44. Osteochondritis dissecans in a 15-year-old girl.
A focal area of radiolucency is evident in the subchondral region of the medial femoral condyle. (From De Smet et al. 1997)
pain (worse at night), tenderness, swelling, and restricted range of movement in the joint (Motohashi
et al. 1991). The medial femoral condyle is affected
most commonly, a typical location being the weightbearing surface. The relation between spontaneous
osteonecrosis of the knee and a subchondral insufficiency fracture has been emphasized recently (Yamamoto et al. 2000). Unilateral involvement predominates over bilateral involvement. If untreated, the lesion can progress toward further depression of the
bony margin, joint space narrowing, intra-articular
osseous bodies, and severe osteoarthritis. Primary
osteonecrosis of the femoral condyle is distinct from
osteochondritis dissecans (OMIM 165800), a disease
affecting adolescents and young adults, and most
typically involving the non-weight-bearing (lateral)
surface of the medial femoral condyle (Aichroth
1971) (Fig. 5.44). Clinical symptoms in osteochondritis dissecans include pain, restricted range of movement in the joint, clicking, and swelling; however,
symptomatology may be entirely lacking. The central
role of trauma in the initiation of this disease is undeniable, as demonstrated by the presence in excised
fragments of osteochondritis dissecans lesions of
viable hyaline articular cartilage only, in the absence
of bone necrosis (Chiroff and Cooke 1975). Thus,
necrosis of the subchondral bone is not primary, but
most probably secondary to trauma. However, a familial history has been documented in several cases
(Robinson et al. 1978). In familial cases osteochon-
Epiphyseal Abnormalities
dritis dissecans often involves multiple sites, and it
may or may not be associated with other skeletal and
nonskeletal defects.Among others, short stature (Andrew et al. 1981; Phillips and Grubb 1985), tibia vara
(OMIM 188700) (Tobin 1957), and an association of
hypertelorism, finger contractures, carpal fusion,
peculiarly shaped ears, sternal deformity, and cryptorchidism resembling Aarskog syndrome (OMIM
305400) (Hanley et al. 1967; Berry et al. 1980) have
been described.
A remarkable form of acquired ischemic necrosis
is that involving the femoral head after traumatic dislocation, which implies rupture of the ligamentum
teres and disruption of the epiphyseal arterial supply.
Patients with intracapsular femoral head fractures
may also develop ischemic necrosis, owing to severe
damage to the sinusoidal vascular bed (Mussbichler
1970). Whether patients with collagen vascular disorders, including systemic lupus erythematosus and
rheumatoid arthritis, and those with lymphoproliferative disorders are at risk of osteonecrosis because of
the primary disease (Wallace 2001) or because of the
treatment, either with immunosuppressant medication (Harper et al. 1984) or with corticosteroids
(Fisher and Bickel 1971), is difficult to establish in
most cases. Osteonecrosis caused by occlusion of the
sinusoidal vascular bed, without evidence of arterial
or venous blood flow interruption, can occur in such
disorders as sickle cell anemia. Occlusion of the sinusoids by the sickled erythrocytes may initiate a cascading process in which anoxia leads to further sickling and sickling leads, in turn, to more extensive vascular occlusion. Epiphyseal and metaphyseal areas of
active hematopoiesis are most commonly involved,
especially those at the distal ends of the humerus,
tibia, and femur (Keeley and Buchanan 1982). The
mechanism of osteonecrosis in patients receiving
steroid therapy remains to be clarified. Arterial occlusion by microscopic fat emboli, perhaps as a consequence of hyperlipidemia, is a tentative explanation (Jones and Sakovich 1966). Increase in the size of
the marrow fat cells, a phenomenon associated with
high-dose steroid therapy, is another possible mechanism that might impair the sinusoidal vascular
bed capacity, via external mechanical compression
(Wang et al. 1977). Similar mechanisms have been
suggested for ischemic necrosis associated with the
chronic use of alcohol (Hungerford and Zizic 1978).
Accumulation of lipid-containing cells in Gaucher
disease (OMIM 230800) is likely to lead to encasement of the vascular bed and, thus, to interruption of
the vascular supply (Wenstrup et al. 2002). Two possible mechanisms are responsible for osteonecrosis
341
related to dysbaric disorders (McCallum 1984). The
first is a direct gas embolization of an arterial vessel
supplying the epiphysis. The second mechanism depends on an acute increase in intraosseous marrow
pressure and venous stasis during unbalanced decompression. Increased intraosseous marrow pressure is due, in turn, to an expanded volume of fat
cells, which are able to absorb the bulk of dissolved
gas (nitrogen) during decompression.
In contrast with the foregoing types of osteonecrosis, in which a recognizable external cause is
implicated, cases of juvenile ischemic necrosis occurring within the same family in several generations
are also encountered. Possible localizations of the ischemic focus in such cases include head of femur
(Legg-Calvè-Perthes, OMIM 150600), tarsal scaphoid
(Köhler, OMIM 165800), semilunar bone of the wrist
(Kienböck, OMIM 165800), head of the 2nd metatarsal (Freiberg, OMIM 165800), capitellum of the
humerus (Panner, OMIM 165800), and phalanges of
the hand (Thiemann, OMIM 165700). For many of
these disorders, a pattern of autosomal dominant inheritance has been suggested. However, the importance of trauma as the precipitating event in most of
these disorders cannot be denied (Douglas and Rang
1981). The unilateral distribution predominates, but
involvement of multiple and bilateral sites is not uncommon. Legg-Calvè-Perthes disease is discussed in
Chapter 4, while Kienböck and Thiemann disease are
briefly reviewed in Chapter 6. Panner disease is a rare
osteonecrotic process involving the capitulum of the
humerus. It occurs almost exclusively in boys, often
athletes, and has a peak incidence between the ages
of 5 and 10 years (Stoane et al. 1995; Singer and Roy
1984). The link between the osteonecrotic process
and repetitive traumas is striking. Clinical manifestations include pain, restricted range of motion of the
elbow, swelling, and local tenderness. Radiographic
features include fissuring and fragmentation of the
capitulum, sclerosis, and increased radiohumeral
space. The process is self-limiting, with reconstitution of the capitulum. Differentiation from osteochondritis dissecans of the elbow is based on patient
age. (Panner disease is a disease of childhood, while
osteochondritis dissecans is a disease of adolescence
or adulthood.)
Fragmentation and flattening of the femoral capital epiphyses closely resembling those of Legg-CalvèPerthes disease are frequently seen in children with
tricho-rhino-phalangeal dysplasia, type I (Giedion
syndrome, OMIM 190350) and type II (LangerGiedion syndrome, OMIM 150230). Possible sequelae
of adulthood include coxa plana, coxa magna, and
342
Chapter 5 · Long Bones
hip osteoarthritis. As anticipated, Blount disease and
bilateral aseptic necrosis of the lateral femoral
condyles occur as part of the autosomal recessive
ear/patella/short stature syndrome (Meier-Gorlin
syndrome, OMIM 224690). Absent patellas, short
stature, microtia and micrognathia are also part of
the constellation of anomalies (Gorlin et al. 1975).
Radiographic Synopsis
AP, LL, and oblique projections (depending on the
anatomic region being investigated). This synopsis
includes a summary of the histological–radiographic
correlation for each of five anatomical phases, from
cell death to articular collapse, that the process of
ischemic necrosis can be divided into (Sweet and
Madewell 1995). The following description refers to
ischemic necrosis of the femoral head, but it applies
to other forms of osteonecrosis, owing to the remarkable similarities of the morphologic findings among
different disorders regardless of their pathogenesis
and anatomic location.
1. Phase I (cellular death): no radiographic evidence
of osteonecrosis.
2. Phase II (cell modulation and hyperemia): area
of radiolucency with coarsened trabeculae surrounding the osteonecrotic focus, and representing bone loss (osteoporosis) attributable to hyperemia and osteoclastic resorption.
3. Phase III (appearance of a reactive interface about
the osteonecrotic focus): focal area of increased
density, representing the zone of osteonecrosis.
4. Phase IV (remodeling of the reactive interface):
the radiodense osteonecrotic focus is outlined by
a radiolucent zone, representing osteoclastic resorption of the advancing fibrous reactive interface); this radiolucent zone is surrounded, in turn,
by a dense area, representing osteoblastic bone
formation.
5. Phase V (crescent sign and articular collapse):
subchondral lucent area (crescent sign) representing subchondral bone plate fracture, best seen using the frog-leg view. Later on, fragmentation and
irregularity of the epiphyseal contour and flattening (collapse) of the articular surface are observed.
Associations
• Alcoholism
• Collagen vascular disorders (SLE, RA)
• Cushing disease
• Diabetes mellitus
• Dysbaric disorders
• Fabry disease
• Freiberg disease
• Gaucher syndrome
• Gout
• Hemophilia
• Histiocytosis X
• Hyperlipoproteinemia
• Hypothyroidism
• Idiopathic
• Irradiation
• Kienböck disease
• Köhler disease
• Legg-Calvè-Perthes disease
• Lymphoproliferative disorders
• Osteochondritis dissecans
• Pancreatitis
• Panner disease
• Polycythemia vera
• Sickle cell anemia
• Steroid therapy
• Thiemann disease
• Trauma
• Tricho-rhino-phalangeal dysplasia, type 1
• Winchester syndrome
References
Aichroth P. Osteochondritis dissecans of the knee. A clinical
survey. J Bone Joint Surg Br 1971; 53: 440–7
Andrew TA, Spivey J, Lindenbaum RH. Familial osteochondritis dissecans and dwarfism. Acta Orthop Scand 1981; 52:
519–23
Arlet J. Nontraumatic avascular necrosis of the femoral head.
Past, present, and future. Clin Orthop 1992; 277: 12–21
Berry C, Cree J, Mann T. Aarskog’s syndrome. Arch Dis Child
1980; 55: 706–10
Chiroff RT, Cooke CP 3rd. Osteochondritis dissecans: a histologic and microradiographic analysis of surgically excised
lesions. J Trauma 1975; 15: 689–96
De Smet AA, Ilahi OA, Graf BK. Untreated osteochondritis dissecans of the femoral condyles: prediction of patient outcome using radiographic and MR findings. Skeletal Radiol
1997; 26: 463–7
Douglas G, Rang M. The role of trauma in the pathogenesis of
the osteochondroses. Clin Orthop 1981; 158: 28–32
Fisher DE, Bickel WH. Corticosteroid-induced avascular
necrosis. A clinical study of seventy-seven patients. J Bone
Joint Surg Am 1971; 53: 859–73
Metaphyseal Abnormalities
Gorlin RJ, Cervenka J, Moller K, Horrobin M, Witkop CJ Jr. A
selected miscellany. Birth Defects Orig Art Ser 1975; 2:
39–50
Hanley WB, McKusick VA, Barranco FT. Osteochondritis dissecans and associated malformations in brothers: a review of
familial aspects. J Bone Joint Surg Am 1967; 49: 925–37
Harper PG, Trask C, Souhami RL. Avascular necrosis of bone
caused by combination chemotherapy without corticosteroids. Br Med J 1984; 288: 267–8
Hungerford DS, Zizic TM. Alcoholism associated ischemic
necrosis of the femoral head. Early diagnosis and treatment. Clin Orthop 1978; 130: 144–53
Jones JP Jr, Sakovich L. Fat embolism of bone. A roentgenographic and histological investigation, with use of intra-arterial lipiodol, in rabbits. J Bone Joint Surg Am 1966; 48:
149–64
Keeley K, Buchanan GR. Acute infarction of long bones in children with sickle cell anemia. J Pediatr 1982; 101: 170–5
McCallum RI. Bone necrosis due to decompression. Philos
Trans R Soc Lond B Biol Sci 1984; 304: 185–91
Motohashi M, Morii T, Koshino T. Clinical course and
roentgenographic changes of osteonecrosis in the femoral
condyle under conservative treatment. Clin Orthop 1991;
266: 156–61
Mussbichler H. Arteriographic findings in necrosis of the head
of the femur after medial neck fracture. Acta Orthop Scand
1970; 41: 77–90
Pavelka K. Osteonecrosis. Baillieres Best Pract Res Clin
Rheumatol 2000; 14: 399–414
Phillips HO, Grubb SA. Familial multiple osteochondritis dissecans: report of a kindred. J Bone Joint Surg Am 1985; 67:
155–6
Resnick D. Osteochondroses. In Resnick D: Diagnosis of bone
and joint disorders. W.B. Saunders Company, Philadelphia,
1995 (3rd ed.), pp. 3559–610
Robinson RP, Franck WA, Carey EJ, Goldberg EB. Familial
polyarticular osteochondritis dissecans masquerading as
juvenile rheumatoid arthritis. J Rheumatol 1978; 5: 190–4
Singer KM, Roy SP. Osteochondrosis of the humeral capitellum. Am J Sports Med 1984; 12: 351–60
Stoane JM, Poplausky MR, Haller JO, Berdon WE. Panner’s disease: X-ray, MR imaging findings and review of the literature. Comput Med Imaging Graph 1995; 19: 473–6
Sweet DE, Madewell JE. Osteonecrosis: pathogenesis. In:
Resnick D: Diagnosis of bone and joint disorders. W.B.
Saunders Company, Philadelphia, 1995 (3rd ed.), pp.
3458–66
Tobin WJ. Familial osteochondritis dissecans with associated
tibia vara. J Bone Joint Surg Am 1957; 39: 1091–105
Trueta J. The normal vascular anatomy of the human femoral
head during growth. J Bone Joint Surg Br 1957; 39: 358–64
Wallace DJ. Clinical correlates of avascular necrosis in systemic lupus erythematosus. J Rheumatol 2001; 28: 2365–6
Wang GJ, Sweet DE, Reger SI, Thompson RC. Fat-cell changes
as a mechanism of avascular necrosis of the femoral head
in cortisone-treated rabbits. J Bone Joint Surg Am 1977; 59:
729–35
Wenstrup RJ, Roca-Espiau M,Weinreb NJ, Bembi B. Skeletal aspects of Gaucher disease: a review. Br J Radiol 2002; 75
[Suppl]: A2–A12
Yamamoto T, Bullough PG. Spontaneous osteonecrosis of
the knee: the result of subchondral insufficiency fracture.
J Bone Joint Surg Am 2000; 82: 858–66
343
Metaphyseal Abnormalities
This section summarizes the characteristics of some
important metaphyseal abnormalities, emphasizing
the key elements for the radiographic diagnosis of
various constitutional bone diseases. Minor metaphyseal abnormalities are common to a number of
disorders and are therefore not very helpful in the
diagnostic process. At the opposite end of the spectrum, some other metaphyseal appearances provide
crucial diagnostic information.
The growth plate, a structure located at both ends
of the long bones between the metaphysis and the
epiphysis, allows for an increase in the length of the
bone and encompasses the following histological
zones (from metaphysis to epiphysis). (1) Zone of primary and secondary spongiosa; bars of cartilage, covered by osteoblasts, are partially or completely calcified. (2) Hypertrophic zone; cells in this zone are large
and vacuolated, and become smaller and metabolically active in the upper portion of the hypertrophic
zone, where calcification of the cartilage matrix is occurring. (3) Proliferating zone: an orderly, longitudinally columnar arrangement of chondrocytes is seen,
and cells in this zone undergo active proliferation
and lay down cartilage matrix. (4) Reserve zone, also
called resting zone or germinal zone. This zone is
located beneath the epiphysis and consists of randomly arranged cartilage cells, possibly with a nutritional function (Brighton 1978). Knowledge of the
anatomy of the growth plate, as outlined above, is important for comprehension of the metaphyseal
changes occurring in association with specific disorders.
Reference
Brighton CT. Structure and function of the growth plate. Clin
Orthop 1978; 136: 22–32
Broad Metaphyses
䉴 [Widening of the metaphyses]
As discussed earlier in this chapter in the section
“Broad Tubular Bones,” broadening of the tubular
bones, including the metaphyses, can be due to defective modeling, bone marrow hyperplasia/infiltration,
or cortical hyperostosis. Failure of normal modeling
at the diaphyseal–metaphyseal junction during
skeletal growth results in broadening and widening
344
Chapter 5 · Long Bones
Fig. 5.45. Metaphyseal dysplasia (Pyle disease). a There
is marked widening of the
metaphyses and adjacent portions of the diaphyses, with a
relatively abrupt transition
zone between the expanded
area and the remainder of the
diaphysis. The cortices are
thin. There is mild bowing of
the tibias and fibulas. (From
Turra et al. 2000) b Same condition in a 17-year-old man.
Similar findings in the long
bones of the forearm
a
b
Fig. 5.46. Osteopetrosis in a 2-year-old boy. Note homogenous
increase in bone density, with indistinctness between medulla
and cortex, and failure of bone modeling with metaphyseal expansion
of the metaphysis. Indeed, the metaphysis is the
anatomical area where the effects of abnormal bone
modeling are most prominent. A specific type of
metaphyseal broadening, referred to as Erlenmeyer
flask deformity, occurs at the distal end of the femur
and consists of marked, club-shaped metaphyseal expansion with osseous margins showing a straightened or convex contour instead of the normal concave contour. Conditions characterized by severe
modeling defects and metaphyseal expansion of the
Erlenmeyer type include metaphyseal dysplasia (Pyle
disease, OMIM 265900) (Fig. 5.45a,b) and craniometaphyseal dysplasia (OMIM 123000, 218400). The tubulation defect about the metaphyses is more severe in
Pyle disease than in craniometaphyseal dysplasia. By
contrast, skull sclerosis is less prominent in the former than in the latter, and is not associated with
cranial nerve compromise. Club-shaped metaphyses
are also observed in osteopetrosis, precocious type
(OMIM 259700) and, to a varying extent, in osteopetrosis, delayed type (OMIM 166600) (Fig. 5.46). In
frontometaphyseal dysplasia (OMIM 305620) metaphyseal widening is not as severe as in the disorders
mentioned earlier. Kniest dysplasia (OMIM 156550)
is characterized by short tubular bones with wide
metaphyses, and unusually large and deformed epiphyses in the child and adult (especially at the knee).
The femoral necks are very broad and short, with
Metaphyseal Abnormalities
unossified femoral capital epiphyses. Platyspondyly
with anterior wedging of the vertebral bodies, occasional coronal clefts in the lumbar spine in infancy,
kyphoscoliosis, and clubfeet are additional findings
(Lachman et al. 1975). Metatropic dysplasia (OMIM
250600) features shortening of the tubular bones,
marked metaphyseal flaring, and epiphyseal dysplasia. The distal femoral ends may show an inverted
V-shape configuration, and the lesser trochanters are
often directed downward, giving the proximal femurs a battle-axe configuration. The degree of metaphyseal widening and of epiphyseal involvement is
usually more severe in metatropic dysplasia than in
Kniest dysplasia. The configuration of the vertebral
bodies, pelvis, and thorax are also different in the two
disorders. In dyssegmental dysplasia (OMIM 224410,
224400), marked expansion of the distal femoral
metaphyses and short, wide long tubular bones are
typical features. Changes are significantly more severe in the early-onset lethal Silverman-Handmaker
disease than in Rolland-Desbuquois disease. In the
latter, changes in the long bones, including metaphyseal widening, resemble those of Kniest dysplasia
(Gorlin and Langer 1978; Aleck et al. 1987). An additional variant of this dysplasia, termed dyssegmental
dysplasia with glaucoma (OMIM 601561) because of
the presence of severe glaucoma and exophthalmos,
has been described recently by Maroteaux et al. in
two unrelated children with severe micromelia,
flared metaphyses, delayed epiphyseal ossification,
platyspondyly, dolichocephaly, and cleft palate
(Maroteaux et al. 1996). Dumbbell-shaped femurs
and humeri (a dumbbell is a short bar with a weight
at each end, used for exercising the muscles) are
typically encountered in Weissenbacher-Zweymuller
syndrome (OMIM 277610), a rhizomelic chondrodysplasia with neonatal micrognathia, midface
hypoplasia, and cleft palate (Chemke et al. 1992),
which has been shown to be the same entity as heterozygous OSMED (nonocular Stickler) syndrome.
The dumbbell femoral configuration is also found in
Schneckenbecken dysplasia (OMIM 269250). Broad
metaphyses are also encountered in fibrochondrogenesis (OMIM 228520), a rare lethal chondrodysplasia
characterized radiographically by very short long
bones, platyspondyly, and short ribs; and microscopically, by fibrous septa around chondrocytes (Lazzaroni-Fossati et al. 1978).
Expanded metaphyses, most commonly associated with cortical thinning, also occur in conditions
characterized by bone marrow infiltration, such as
lipid storage diseases (e.g. Gaucher’s, Niemann-Pick)
(Matsubara et al. 1982), or reactive bone marrow
hyperplasia, such as severe chronic anemias. In addi-
345
tion to bone marrow infiltration, defective modeling
accounts for metaphyseal widening in lipid storage
diseases, especially in the lower ends of the femoral
shafts (Lachman et al. 1973). In mucopolysaccharidoses, diaphyseal and metaphyseal expansion in the
long bones, associated with cortical thinning, are features of the more complex skeletal spectrum referred
to as dysostosis multiplex and consisting of dolichocephalic skull, underdeveloped sinuses, hook-shaped
vertebrae with thoracolumbar gibbus, platyspondyly,
underdeveloped acetabula, hip dysplasia, coxa valga,
wide ribs, thick, short clavicles, brachydactyly, deformed carpal bones, and osteoporosis. Changes in
the skeleton are related to the widespread intracellular accumulation of abnormal glycosaminoglycans,
with bone marrow expansion, and interference with
the normal function of chondrocytes (Yoshida et al.
1993).
Radiologic manifestations of lead poisoning
(plumbism) include transverse radiodense metaphyseal bands in the growing tubular bones, widening of
the cranial sutures due to increased intracranial
pressure, and metaphyseal widening of the tubular
bones (Pease and Newton 1962).
Radiographic Synopsis
AP projection
1. Erlenmeyer flask configuration of distal femur;
thin cortices (metaphyseal dysplasia, cranio-metaphyseal dysplasia)
2. Dense bones; bone-in-bone appearance; clubshaped metaphyses; transverse metaphyseal bands
(osteopetrosis)
3. Dumbbell appearance of femurs; short tubular
bones (Kniest dysplasia, dyssegmental dysplasia,
metatropic dysplasia)
4. Undermodeled shafts and metaphyses; thin cortices; bone rarefaction (mucopolysaccharidoses)
Associations
• Anemia, severe
• Chronic lead poisoning
• Cockayne syndrome
• Craniometadiaphyseal dysplasia,
wormian bone type
• Craniometaphyseal dysplasia
• Diastrophic dysplasia
• Dysosteosclerosis
• Dyssegmental dwarfism
• Dyssegmental dysplasia with glaucoma
• Fibrochondrogenesis
• Frontometaphyseal dysplasia
• Gaucher disease
• Histiocytosis X
346
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Chapter 5 · Long Bones
Hypertrichosis-osteochondrodysplasia
Infantile multisystem inflammatory disease
Kniest dysplasia
Kniest-like dysplasia-pursed lips–ectopia lentis
Mastocytosis
Membranous lipodystrophy
Metaphyseal dysplasia (Pyle disease)
Metatropic dysplasia
Mucopolysaccharidoses
Niemann-Pick disease
Oculo-dento-osseous dysplasia
Osteodysplasty (Melnick-Needles)
Osteopetrosis
Oto-spondylo-megaepiphyseal dysplasia
Pseudoachondroplasia
Schneckenbecken dysplasia
Spondylo-megaepiphyseal-metaphyseal dysplasia
Ulnar metaphyseal dysplasia syndrome
Weissenbacher-Zweymuller syndrome
References
Aleck KA, Grix A, Clericuzio C, Kaplan P, Adomian GE, Lachman R, Rimoin DL. Dyssegmental dysplasias: clinical, radiographic, and morphologic evidence of heterogeneity. Am
J Med Genet 1987; 27: 295–312
Chemke J, Carmi R, Galil A, Bar-Ziv Y, Ben-Ytzhak I, Zurkowski L.Weissenbacher-Zweymuller syndrome: a distinct autosomal recessive skeletal dysplasia. Am J Med Genet 1992;
43: 989–95
Gorlin RJ, Langer LO Jr. Dyssegmental dwarfism(?s): lethal
anisospondylic camptomicromelic dwarfism. Birth Defects
Orig Art Ser 1978; 6B: 193–7
Lachman R, Crocker A, Schulman J, Strand R. Radiological
findings in Niemann-Pick disease. Radiology 1973; 108:
659–64
Lachman RS, Rimoin DL, Hollister DW, Dorset JP, Siggers DC,
McAlister W, Kaufman RL, Langer LO. The Kniest syndrome. Radiology 1975; 123: 805–9
Lazzaroni-Fossati F, Stanescu V, Stanescu R, Serra G, Magliano
P, Maroteaux P. La fibrochondrogenese. Arch Fr Pediatr
1978; 35: 1096–104
Maroteaux P, Manouvrier S, Bonaventure J, Le Merrer M.
Dyssegmental dysplasia with glaucoma. Am J Med Genet
1996; 63: 46–9
Matsubara T, Yoshiya S, Maeda M, Shiba R, Hirohata K. Histologic and histochemical investigation of Gaucher cells. Clin
Orthop 1982; 166: 233–42
Pease CN, Newton GB. Metaphyseal dysplasia due to lead poisoning. Radiology 1962; 79: 233–40
Turra S, Gigante C, Pavanini G, Bardi C. Spinal involvement in
Pyle’s disease. Pediatr Radiol 2000; 30: 25–7
Yoshida M, Ikadai H, Maekawa A, Takahashi M, Nagase S.
Pathological characteristics of mucopolysaccharidosis VI
in the rat. J Comp Pathol 1993; 109: 141–53
Metaphyseal Cupping
䉴 [Inward bulging of the metaphyseal profile]
Metaphyseal cupping occurs most commonly as a
widespread defect in systemic diseases, such as
metabolic disorders or skeletal dysplasias. However,
involvement of a single metaphysis can also be observed, for example in children after focal injuries to
the growth plate. Fractures extending across the epiphysis, the growth plate, and the metaphysis (type II
and type IV growth plate injury) (Salter and Harris
1963) may give rise, during the healing process, to the
formation of a bony bridge between the epiphysis
and corresponding metaphysis in the area where
germinal proliferating cells have been violated. The
bony bridge causes premature partial arrest of
growth at that point without affecting growth in the
remainder of the physis, thereby producing an angular deformity (Peterson 1984). With injuries located
centrally in the growth plate, metaphyseal cupping
may be the result. Less common causes of bony bars
at the growth plate include thermal injury, infection
(Fig. 5.47a–c), radiation therapy, neoplasms, and surgical procedures (Sanpera et al. 1994).
Rickets is a striking example of a metabolic disorder featuring metaphyseal cupping. Lesions in rickets are typically located at the growth plate, the most
frequently involved areas being the provisional zone
of calcification and the hypertrophic zone. The provisional zone shows defective mineralization and
lack of proper bone formation, while the hypertrophic zone displays loss of its orderly columnar
arrangement and transformation into a thick, grossly disorganized mass of cartilaginous cells. As a result of this abnormal cell mass placed longitudinally
and transversely within the growth plate, widening
and cupping of the metaphyses occur (Fig. 5.48).
Cupping has been explained as the effect of inward
protrusion of the cartilaginous cell mass at the center of the growth plate (Mankin 1974). The provisional calcification zone is undermineralized, metaphyses are irregular and frayed, and epiphyseal centers are poorly ossified and indistinct. Osteomalacic
and rachitic changes are associated with various
conditions: (a) disorders of vitamin D metabolism;
(b) hypophosphatemic vitamin D-refractory syndromes related to primary renal tubular loss of
phosphate; and (c) ‘idiopathic’ syndromes, in which
there are no detectable abnormalities of vitamin D,
calcium, or phosphorus metabolism. Rickets-like
changes in the metaphysis are also seen in patients
with hypophosphatasia tarda (OMIM 146300) in as-
Metaphyseal Abnormalities
b
a
Fig. 5.47 a–c. Chronic recurrent multifocal
osteomyelitis. a In a 9-year-old boy an irregular lytic lesion surrounded by a sclerotic reaction is apparent within the distal
metaphysis of the radius. b In the same boy
at 13 years of age note the abnormal bony
bridging across the growth plate. c In the
images taken when the boy was 16 years old
there is cupping of the radial end with marginal spurs and premature osteoarthritis.
(From Piddo et al. 2000)
sociation with fragile and bowed long bones, where
the changes resemble those seen in osteogenesis imperfecta. Irregular, frayed metaphyses are typically
associated with large unossified metaphyseal defects
that extend a long way into the diaphysis (Fig. 5.49a–c).
Cupping and splaying of the distal femoral metaphyses, sometimes with invagination of the corresponding epiphyses, are typically seen in patients affected by chronic vitamin A intoxication. Other radiographic signs include cortical hyperostosis, which
347
c
is most prominent in the ulna and the metatarsals,
and widening of the cranial sutures as a result of increased intracranial pressure (Caffey 1950). Widening and cupping of the metaphyses, and especially of
those about the wrist, are seen in phenylketonuria
(OMIM 261600), a metabolic disorder with an autosomal recessive inheritance, which is due to deficiency of hepatic phenylalanine hydroxylase and
failed conversion of phenylalanine to tyrosine. Affected children usually have neurological symptoms,
348
Chapter 5 · Long Bones
Fig. 5.48. Rickets in a 14-month-old boy. The metaphyses
are cupped and frayed, with disorganized growth plate. Observe the coarse trabecular pattern reflecting poor mineralization
Fig. 5.49. a Infantile and
b, c juvenile hypophosphatasia tarda. a In this 2-day-old
male neonate observe large
ossification defects in the
ends of the long bones. No
long bone angulation is apparent in this child. Bone
mineralization is defective.
Features are reminiscent of
rickets. b In this newborn girl
no metaphyseal defects can be
detected at the proximal
humeral metaphysis. c Same
patient as in b but at age
6 months. Marked humeral
metaphyseal changes have developed, with large unossified
metaphyseal defects extending into the diaphysis. (From
Giedion 1994)
a
b
including tremor, athetosis, dystonia, mental retardation, seizures, eczema, and increased serum levels
of phenylalanine and urinary levels of phenylpyruvic
acid (Taybi 1990). Characteristic radiographic
changes are calcified lines of cartilage projecting
from the metaphysis into the growth plate
(Woodring and Rosenbaum 1981).
Metaphyseal cupping is also a feature of several
bone dysplasias. In achondroplasia (OMIM 100800),
a peculiar radiographic evolution pattern is recognized at the distal end of the femur. The metaphysis
is flared and medially slanted in the young child. In
later years, the metaphysis becomes centrally
cupped, with an inverted ‘V’ configuration that encloses the corresponding epiphysis giving rise to the
ball-in-socket appearance. Metaphyseal abnormalities are seen at the proximal end of the tibia. Mild
metaphyseal flaring also occurs in hypochondroplasia (OMIM 146000), an autosomal dominant disorder caused by a mutation in the gene for fibroblast
growth factor receptor-3 (FGFR3, OMIM 134934),
which is located at 4p and is also mutated in achondroplasia. Overall, findings in hypochondroplasia
are similar to, but less severe than, those of achondroplasia (Fig. 5.50). Because the clinical and radi-
c
Metaphyseal Abnormalities
349
Radiographic Synopsis
AP projections
1. Cupping of a single metaphysis; absence of significant metaphyseal irregularities (type II and type
IV growth plate injury)
2. Widened, cupped, and frayed metaphyses; undermineralized metaphyses; small, underossified epiphyses (rickets)
3. Rickets-like metaphyseal changes; large unossified metaphyseal defects; fragile, bowed long
bones (hypophosphatasia tarda)
4. Cupped, splayed distal femoral metaphyses; cortical hyperostosis (vitamin A intoxication)
5. In infancy, flaring and medial slanting of distal
femoral metaphysis; in childhood, inverted V
metaphyseal appearance; mild metaphyseal abnormalities of proximal tibia (achondroplasia)
6. Markedly irregular, widened, cupped metaphyses;
small and dysplastic epiphyses (pseudoachondroplasia)
7. Severely cupped metaphyses at the knee; coneshaped epiphyses; deformed femoral condyles
(metaphyseal acroscyphodysplasia)
Fig. 5.50. Hypochondroplasia. Note short stubby tibia, with
mild metaphyseal flaring and cupping. The fibula is longer
than the tibia. (From Prinster et al. 2001)
ographic manifestations are often evanescent, this
disorder is underdiagnosed. Some authors maintain
that the diagnosis can be confidently made in the
presence of short stature, normal craniofacies, and
lack of the normal craniocaudal increase in the interpediculate distance in the lumbar spine (Appan et
al. 1990). In pseudoachondroplasia (OMIM 177170),
widened, strikingly irregular metaphyses are major
radiographic features; the epiphyses are small and
deformed. Markedly cup-shaped metaphyses about
the knees, with cone-shaped epiphyses, have been
described as peculiar to metaphyseal acroscyphodysplasia (OMIM 250215) (Verloes et al. 1991), this designation referring to cupping (scyphus) of the metaphyses in the limbs (acro). Other findings originally
described in two affected sibs included severe
growth retardation, short, broad tubular bones especially in the lower limbs, deformation of the femoral
condyles, coxa valga, knee flexion, severe brachydactyly with short middle phalanges, and coneshaped phalangeal and metacarpal epiphyses (Bellini et al. 1984).
Associations
• Achondrogenesis type I (Parenti-Fraccaro)
• Achondroplasia
• Bone infarction
• Cephaloskeletal dysplasia (Taybi-Linder)
• Chondroectodermal dysplasia (Ellis-Van Creveld)
• Congenital indifference to pain
• Copper deficiency
• Dyssegmental dysplasia
• Hypervitaminosis A
• Hypochondroplasia
• Hypophosphatasia
• Infection
• Menkes’ kinky hair syndrome
• Metaphyseal acroscyphodysplasia (Bellini)
• Metaphyseal chondrodysplasias (all types)
• Mucolipidoses
• Neoplasms
• Peripheral dysostosis
• Phenylketonuria
• Pseudoachondroplasia
• Radiation therapy
• Rickets
• Surgical procedures
• Thanatophoric dysplasia
• Thermal injury
• Trauma
• Tricho-rhino-phalangeal syndromes
350
Chapter 5 · Long Bones
References
Appan S, Laurent S, Chapman M, Hindmarsh PC, Brook CGD.
Growth and growth hormone therapy in hypochondroplasia. Acta Paediatr Scand 1990; 79: 796–803
Bellini F, Chiumello G, Rimoldi R,Weber G.Wedge-shaped epiphyses of the knees in two siblings: a new recessive rare
dysplasia? Helv Paediatr Acta 1984; 39: 365–72
Caffey J. Chronic poisoning due to excess of vitamin A. Description of the clinical and roentgen manifestations in
seven infants and young children. Pediatrics 1950; 5: 672–8
Giedion A. The weight of the fourth dimension for the diagnosis of genetic bone disease. Pediatr Radiol 1994; 24: 387–91
Mankin HJ. Rickets, osteomalacia, and renal osteodystrophy.
Part II. J Bone Joint Surg Am 1974; 56: 352–86
Peterson HA. Partial growth plate arrest and its treatment.
J Pediatr Orthop 1984; 4: 246–58
Piddo C, Reed MH, Black GB. Premature epiphyseal fusion and
degenerative arthritis in chronic recurrent multifocal
osteomyelitis. Skeletal Radiol 2000; 29: 94–6
Prinster C, Del Maschio M, Beluffi G, Maghnie M, Weber G, Del
Maschio A, Chiumello G. Diagnosis of hypochondroplasia:
the role of radiological interpretation. Italian Study Group
for Hypochondroplasia. Pediatr Radiol 2001; 31: 203–8
Salter RB, Harris WR. Injuries involving the epiphyseal plate.
J Bone Joint Surg Am 1963; 45: 587–92
Sanpera I Jr, Fixsen JA, Hill RA. Injuries to the physis by extravasation. A rare cause of growth plate arrest. J Bone Joint
Surg Br 1994; 76: 278–80
Taybi H. Metabolic disorders. In: Taybi H, Lachman RS (eds.)
Radiology of syndromes, metabolic disorders, and skeletal
dysplasias. Year Book Medical Publishers Inc., Chicago,
1990 (3rd ed.), pp. 633–4
Verloes A, Le Merrer M, Farriaux JP, Maroteaux P. Metaphyseal
acroscyphodysplasia. Clin Genet 1991; 39: 362–9
Woodring JH, Rosenbaum HD. Bone changes in phenylketonuria reassessed. AJR Am J Roentgenol 1981; 137: 241–3
Metaphyseal Spurs
䉴 [Osseous beaking at the edges of the metaphysis]
Bony outgrowths extending longitudinally from the
metaphyseal margins are found in a known group of
metabolic disorders and skeletal dysplasias and are
therefore of diagnostic importance in the recognition of specific diseases.
The small metaphyseal excrescences observed in
scurvy are lateral extensions of the abnormal provisional zone of calcification (Nerubay and Pilderwasser 1984). Nutritional copper deficiency (hypocupremia) can be seen in malnourished children, in
children receiving long-term parenteral nutrition,
and in premature infants who are fed a diet low in
copper. Skeletal changes resemble those of scurvy,
and include metaphyseal transverse radiodense lines
and spurs, osteopenia, fractures, periostitis, and
Fig. 5.51. In a 14-month-old boy with Menkes’ kinky hair syndrome the distal femoral and proximal tibial metaphyses are
flared and irregular, with marginal spurs. Bone mineralization
is defective
epiphyseal displacement (Allen et al. 1982). These
changes are reversed by supplementing the diet
with copper. Menkes’ kinky hair syndrome (OMIM
309400) is a rare but severe X-linked recessive condition with mutations in the ATP7A gene (Vulpe et al.
1993). The disorder is due to a defect in copper absorption from the gut. As a consequence, low levels of
copper and ceruloplasmin are found in the blood.
Skeletal changes are similar to those of nutritional
copper deficiency, including osteoporosis and metaphyseal widening with spurs (Fig. 5.51), metaphyseal
fractures, multiple wormian bones, flaring of the
ends of the ribs, small mandible, and scalloping of
the posterior surface of the vertebral bodies (Danks
et al. 1972), and are reversed with early copper supplementation. Clinical manifestations include profound failure to thrive, progressive nervous system
degeneration with early-onset neurological symptoms (hypertonia, seizures, intracranial hemorrhage,
hypothermia), skin hypopigmentation, and steely,
kinky, sparse hair (Danks et al. 1972). In short
rib-polydactyly syndrome, type I (Saldino-Noonan,
OMIM 263530) the long bones are markedly short,
Metaphyseal Abnormalities
with a pointed or ragged appearance of their ends.
This appearance may make them indistinguishable
from true metaphyseal spurs. The short tubular
bones in the hands, the fibulas, and the vertebrae are
only partly ossified. In short rib-polydactyly syndrome, type III (Verma-Naumoff, OMIM 263510) the
long bones are short, with widened metaphyses and
metaphyseal spurs. Signs that both these types have
in common are narrow thorax with extremely short
ribs, short, squared scapulae, and squared iliac
bones. In summary, the Verma-Naumoff type of
short rib-polydactyly syndrome is characterized by
more prominent metaphyseal spurs and better
formed tubular bones than are seen in SaldinoNoonan syndrome (Verma et al. 1975; Naumoff et al.
1977; Sillence 1980). In achondrogenesis type IA and IB
(OMIM 200600, 600972) the tubular bones are
extremely short and wide, with cupped ends and
marginal metaphyseal spurs (van der Harten et al.
1988). The autosomal recessive ‘severe combined immunodeficiency (SCID) with adenosine deaminase
(ADA) deficiency’ (OMIM 102700) is characterized
by recurrent infections that often prove fatal in early
infancy and are related to the absence of cellular and
humoral immunity. Very low levels of ADA activity
are detected in the blood cells, including erythrocytes, lymphocytes, and mononuclear cells, and also
in tissue fibroblasts. Radiologic manifestations include irregular metaphyses of long bones, with metaphyseal spurs, rib shortening with flared ends, mild
platyspondyly, ‘bone-within-bone’ appearance of the
vertebral bodies, squared iliac wings, and absence of
the thymus revealed by chest radiograms (Chakravartie et al. 1991).
Unilateral osseous beaking at the metaphyseal
edge can be seen in children during the healing phase
of a corner fracture (type II growth plate injury), in
which the fracture line, after splitting the growth
plate, enters the metaphysis and creates a triangular
fragment. The bony fragment usually rejoins easily to
the metaphysis, owing to the intact periosteum on its
side, and a beak-like bony outgrowth becomes manifest at the edge. In the abused child syndrome, several
corner fractures can be seen in various stages of
healing (Galleno and Oppenheim 1982).
A peculiar type of metaphyseal beaking that is
very different from the spurs occurring in systemic
disorders is encountered at the proximal tibia and
distal femur in physiological bowleg (Hansson and
Zayer 1975), Blount disease (OMIM 259200), and
conditions associated with genu varum.
351
Radiographic Synopsis
AP projections. Spurs arising at the medial and lateral metaphyseal margin may not be distinguishable
from simple metaphyseal cupping.
1. Small beak-like metaphyseal outgrowths; transverse radiodense lines; osteoporosis; periostitis;
fractures; dysplastic epiphyses (scurvy, copper deficiency, Menkes’ kinky hair syndrome)
2. Very short tubular bones, with pointed/ragged
ends; unossified large portions of bones (short ribpolydactyly syndrome, type I); short tubular bones
with metaphyseal spurs (short rib-polydactyly syndrome, type III)
3. Extremely short long bones; wide shafts; cupped
metaphyses with peripheral, irregular spurs
(achondrogenesis type I)
4. Metaphyses irregularities; metaphyseal spurs (SCID
with ADA deficiency)
5. Unilateral metaphyseal spur; single or multiple
metaphyses involved (corner fracture, battered
child syndrome)
Associations
• Achondrogenesis type I (Parenti-Fraccaro)
• Copper deficiency
• Immune deficiency, severe combined, and adenosine deaminase deficiency (SCID with ADA deficiency)
• Menkes’ kinky hair syndrome
• Scurvy
• Short rib-polydactyly syndrome, type I and III
• Trauma
References
Allen TM, Manoli A 2nd, LaMont RL. Skeletal changes associated with copper deficiency. Clin Orthop 1982; 168: 206–10
Chakravarti VS, Borns P, Lobell J, Douglas SD. Chondroosseous
dysplasia in severe combined immunodeficiency due to
adenosine deaminase deficiency (chondroosseous dysplasia in ADA deficiency SCID). Pediatr Radiol 1991; 21: 447–8
Danks DM, Campbell PE, Stevens BJ, Mayne V, Cartwright E.
Menkes’s kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics 1972; 50:
188–201
Danks DM, Stevens BJ, Campbell PE. Menkes kinky hair syndrome. Lancet 1972; I: 1100–6
Galleno H, Oppenheim WL. The battered child syndrome revisited. Clin Orthop 1982; 162: 11–9
Hansson LI, Zayer M. Physiological genu varum. Acta Orthop
Scand 1975; 46: 221–9
Naumoff P, Young LW, Mazer J, Amortegui AJ. Short-rib-polydactyly syndrome type 3. Radiology 1977; 122: 443–7
352
Chapter 5 · Long Bones
Nerubay J, Pilderwasser D. Spontaneous bilateral distal
femoral physiolysis due to scurvy. Acta Orthop Scand 1984;
55: 18–20
Sillence DO. Non-Majewski short rib-polydactyly syndrome.
Am J Med Genet 1980; 7: 223–9
Van der Harten HJ, Brons JT, Dijkstra PF, Niermeyer MF, Meijer CJ, van Giejn HP, Arts NF. Achondrogenesis-hypochondrogenesis: the spectrum of chondrogenesis imperfecta. A
radiological, ultrasonographic, and histopathologic study
of 23 cases. Pediatr Pathol 1988; 8: 571–97
Verma IC, Bhargava S, Agarwal S. An autosomal recessive form
of lethal chondrodystrophy with severe thoracic narrowing, rhizoacromelic type of micromelia, polydactyly and
genital anomalies. Birth Defects Orig Art Ser 1975; 6:
167–74
Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence
that it encodes a copper-transporting ATPase. Nat Genet
1993; 3: 7–13
Metaphyseal Bands
䉴 [Radiodense and/or radiolucent striations
about the metaphyses, oriented transversely
or longitudinally]
Transverse radiodense bands, also referred to as Park
or Harris lines (Park and Richter 1953; Harris 1926),
stress lines, or growth arrest lines (Garn et al. 1968),
are common in both children and adults. They may
be present at birth or appear during infancy, do not
form after skeletal growth has ceased, and tend to
persist into adulthood. Radiodense lines are more
frequent at sites of rapid bone growth, such as the
distal femurs and proximal tibias, and are not associated with any clinical symptomatology. In the tubular
bones, they run parallel to the provisional zone of
calcification.Although their pathogenesis is not completely understood, there is some evidence supporting the idea that they represent periods of renewed or
increased growth of the bone following a period of
inhibited growth. Therefore, the term ‘recovery’ lines
seems more appropriate than ‘arrest’ lines (Garn et al.
1968). Transverse radiodense bands can be found in
healthy (anatomical variation) individuals and in
those with symptoms, especially patients who have
been poisoned with any of a variety of heavy metals.
In particular, lead poisoning is associated with the
presence of thick radiodense bands in the metaphyses of the tubular bones. Single bands are more typical, but multiple bands can result from several
episodes of lead poisoning. These lines have been related to a disturbance in arterial blood supply to the
cartilage plate, with secondary deposition of calcium
within the cartilaginous matrix. Additional manifes-
tations of chronic lead poisoning include metaphyseal widening of the tubular bones and increased intracranial pressure (Resnick 1995). Virtually every
insult to the growing skeleton, whether from a systemic or a local (trauma, infection) disorder, can produce metaphyseal recovery bands, owing to a transient failure of bone growth. In cases in which no
such episodes are recognized, radiodense lines are
likely to represent exuberant calcification of the provisional zone. Anatomically, radiodense lines consist
of transversely oriented trabeculae crossing the
medullary cavity partially or completely (Pease and
Newton 1962). In the initial stage of bone growth
arrest they appear as thin bony bands lying beneath
the proliferating zone of the growth plate. During the
recovery phase, cartilaginous proliferation and increased osteoblastic activity lead to thickening of the
transverse lines and their migration towards the
metaphysis. Thick, transverse metaphyseal lines of
increased density are typically found in children
with scurvy. These lines correspond histologically to
areas of calcified cartilage matrix lying beneath an
area of irregular arrangement of cartilage cells in the
proliferating zone of the growth plate. The calcified
matrix might eventually extend laterally to form
small beak-like outgrowths. Under this line a radiolucent transverse band (the ‘scurvy’ line) is recognized, which corresponds to decreased trabecular
structure in the junctional area. Other radiographic
changes in scurvy include periostitis, caused by subperiosteal hemorrhage with elevation and stimulation of the periosteum, and a peculiar appearance of
the epiphyses, with a central radiolucency (atrophy of
central spongiosa) surrounded by a sclerotic shell
(prominent provisional zone of calcification) (Garn
et al. 1968). Radiodense lines extending part-way or
right across the marrow cavity in the metaphysis or
in the diaphysis of the tubular bones are found in
association with chronic osteoporosis, usually secondary to limb disuse of neurological or traumatic
origin or to prolonged bed rest. The origin of these
lines, also commonly termed ‘bone bars’ or ‘reinforcement lines,’ is unknown. They may well be preexisting normal structures disclosed by the intervening osteopenia; or they may represent an abnormal
bony response to biomechanical stress (Ogden 1984).
While radiodense bands reflect rapid bone deposition of the recovery phase, radiolucent transverse
bands usually reflect deficient endochondral bone
formation. Symmetrical metaphyseal radiolucent
bands are found in childhood leukemia. Since histologically these bands are not associated with
leukemic cell infiltration, they probably reflect a nu-
Metaphyseal Abnormalities
Fig. 5.52. Leukemia in a 3-year-old child. Note typical transverse metaphyseal lucent bands in the distal femoral and proximal tibial metaphyses. Also observe the radiodense bands adjacent to the areas of increased radiolucency, probably reflecting periods of cessation and acceleration of bone growth.
(From Wihlorg et al. 2001)
Fig. 5.53. Osteopetrosis: a 4-year-old girl affected by the asynchronous asymmetrical form of heterogeneous osteopetrosis
(same case as in Fig. 4.30). Observe the single sclerotic band in
the distal left radius, in contrast with the multiple alternating
sclerotic bands in the distal right radius. Also observe metaphyseal clubbing of the right radius. (From Young and Lachman 2001)
353
Fig. 5.54. Osteopathia striata with cranial sclerosis in an 8year-old girl. There are vertical linear densities in metaphyses
of proximal tibias and distal femurs bilaterally. (From Gay et
al. 1994)
tritional deficit interfering with normal osteogenesis.
The radiolucent bands are areas of bone weakening,
and as such can undergo pathologic fracture or epiphyseal separation and displacement. Associated
areas of radiodensity, probably reflecting alternating
periods of arrest and acceleration of bone growth,
may be seen adjacent to the areas of increased radiolucency in children with leukemia (Nixon and
Gwinn 1973) (Fig. 5.52). Epiphyseal destruction,
osteolytic lesions, diffuse osteopenia, periostitis, and
osteosclerosis are other common skeletal features in
childhood leukemia. Radiolucent metaphyseal bands
are also encountered, although less frequently, in
adult acute leukemia. Again, osteopenia and discrete
osteolytic lesions are additional possible manifestations (van Slyck 1972). Bilateral and symmetrical
band-like metaphyseal radiolucencies can be seen in
children with neuroblastoma, representing secondary localization of the disease. The femur and tibia
are most commonly involved. Sclerotic bands are less
frequent in this disease, usually appearing in late
stages (McAlister and Lester 1971). Lytic lesions and
periostitis are other skeletal manifestations of the
disease.
Alternating radiolucent and sclerotic transverse
metaphyseal bands are consistent features in both
the benign (OMIM 166600) and the malignant
(OMIM 259700) forms of osteopetrosis. They repre-
354
Chapter 5 · Long Bones
Fig. 5.55 a, b. SPONASTRIME
dysplasia. a In a 24-month-old
boy the metaphyses of distal
femur and proximal tibia are
lined with a dense transverse
band, but no vertical striations can be seen. b In this
8-year-old girl note increased metaphyseal irregularities
and vertical striation of alternating dense and lucent areas
next to the metaphyseal margins. (From Langer et al. 1997)
a
b
sent areas of mature bone interspersed with disorganized, sclerotic osseous tissue. In rare instances,
the transverse bands develop in an asynchronous
and asymmetrical fashion between the sides (Young
and Lachman 2001) (Fig. 5.53). Occasionally, vertical
striations are also seen, probably representing blood
vessels surrounded by connective tissue (McAlister
and Herman 1995). Diffuse bone sclerosis, lack of
corticomedullary differentiation, defective modeling
with Erlenmeyer flask deformity, and splayed, radiolucent metaphyses are important skeletal changes in
the long bones in these conditions.
Dense vertical striations about the metaphyses are
less common than transverse bands and are found in
a selected group of disorders. However, prominent
vertical trabecular formation may also represent
normal anatomical variation in otherwise normal
subjects. Osteopathia striata is a rare disease, probably with an autosomal dominant pattern of inheritance, which is characterized by vertical, fine bands
of increased radiodensity extending from the metaphyses of the long bones for a variable distance into
the diaphyses and alternating with areas of bone
rarefaction. The iliac bones are also involved, with
dense striations, while the small bones in the hands
and feet, the skull and facial bones, and the vertebrae
are usually spared. The lesions are most commonly
bilateral and symmetrical, but unilateral distribu-
tions can be seen (Carlson 1977). Osteopathia striata
can occur in association with other sclerosing disorders, such as osteopoikilosis, melorheostosis, and
osteopetrosis (Cantatore et al. 1991). Osteopathia striata with cranial sclerosis (OMIM 166500) has been
identified as a separate entity. Vertical striations of
the long bones in both diseases are remarkably similar, but cranial sclerosis, especially involving the skull
base, cranial nerve palsies, macrocephaly, cleft palate,
and mental retardation are distinct features in the
latter condition (Winter et al. 1980) (Fig. 5.54). A disorder in which the radiographic appearance may
not be distinguishable from osteopathia striata is
SPONASTRIME dysplasia (OMIM 271510). The
acronym SPO-NA-STRI-ME summarizes the principal features of the condition, namely spondylar and
nasal alterations, and striations about the metaphyses. However, the metaphyseal striations are usually
not present in infancy, and they may be inconspicuous in childhood (Fig. 5.55a,b) (Langer et al. 1997).
In the first report by Fanconi et al. (1983), the characteristics of the condition were listed as short-limb
dwarfism, moderate deformity of the vertebral bodies, mildly striated metaphyses, saddle nose, frontal
bossing, large head with midfacial hypoplasia (oriental look), and normal intelligence. Further reports
outlined a variety of SPONASTRIME dysplasia with
mental retardation (Camera et al. 1993; Verloes et al.
Metaphyseal Abnormalities
1995). Vertical striations of the metaphyses crossing
the epiphyses are also seen in focal dermal hypoplasia (Goltz syndrome, OMIM 305600), together with
osteopenia and multiple bone lesions resembling
giant cell tumors. Vertical dense metaphyseal
spicules representing calcified lines of cartilage projecting from the metaphysis into the growth plate are
seen also in phenylketonuria (OMIM 261600). Growth
‘arrest’ lines can also be present. Metaphyses, especially about the wrist, are widened and cup-shaped.
Radiographic Synopsis
AP projections
1. One or multiple transverse radiodense lines, running parallel to the physeal plate and extending
across the medullary cavity (stress lines of Park or
Harris)
2. Single or multiple thick transverse radiodense
metaphyseal lines; metaphyseal widening and
flaring (lead poisoning)
3. Thick transverse radiodense metaphyseal lines;
small metaphyseal spurs; radiolucent transverse
band lying beneath the sclerotic lines; periostitis;
epiphyseal dysplasia (scurvy)
4. Bilateral and symmetrical transverse radiolucent
metaphyseal bands; discrete osteolytic lesions;
osteopenia; periostitis; osteosclerosis (leukemia,
neuroblastoma)
5. Sclerotic bones; transverse radiolucent metaphyseal bands; club-shaped metaphyses; bone-inbone appearance (osteopetrosis)
6. Dense vertical metaphyseal striations (osteopathia
striata, osteopathia striata with cranial sclerosis,
SPONASTRIME dysplasia)
7. Vertical metaphyseal striations extending across
epiphyses; osteopenia; multiple giant cell-like
bone tumors (focal dermal hypoplasia syndrome)
8. Vertically oriented, calcified metaphyseal lines; inconstant transverse dense lines; widened, cupped
metaphyses (phenylketonuria)
Associations
• Battered child syndrome
• Biphosphonate therapy
• Chemotherapy
• Focal dermal hypoplasia (Goltz syndrome)
• Heavy metal or chemical intoxication
• Hypercalcemia, idiopathic
• Hypermagnesemia
• Hypervitaminosis D
• Hypophosphatasia
• Hypothyroidism, treated
355
• Infections, prenatal (toxoplasma, rubella,
cytomegalovirus, herpes)
• Lead intoxication, chronic
• Neoplasms (leukemia, lymphoma, neuroblastoma,
metastases)
• Normal variants
• Osteopathia striata
• Osteopathia striata with cranial sclerosis
• Osteopetrosis
• Osteoporosis
• Phenylketonuria
• Radiation therapy
• Rickets
• Scurvy
• SPONASTRIME dysplasia
• Systemic diseases, long standing
• Trauma
• Vitamin D intoxication
References
Camera G, Camera A, Gatti R. SPONASTRIME dysplasia: report on two siblings with mental retardation. Pediatr Radiol 1993; 23: 611–4
Cantatore FP, Carrozzo M, Loperfido MC. Mixed sclerosing
bone dystrophy with features resembling osteopoikilosis
and osteopathia striata. Clin Rheumatol 1991; 10: 191–5
Carlson DH. Osteopathia striata revisited. J Can Assoc Radiol
1977; 28: 190–2
Fanconi CI, Giedion A, Prader A. The SPONASTRIME dysplasia: familial short-limb dwarfism with saddle nose, spinal
alterations and metaphyseal striation. Helv Paediatr Acta
1983; 38: 267–80
Garn SM, Hempy HO 3rd, Schwager PM. Measurement of localized bone growth employing natural markers. Am J Phys
Anthropol 1968; 28: 105–8
Garn SM, Silverman FN, Hertzog KP, Rohmann CG. Lines and
bands of increased density. Their implication to growth
and development. Med Radiogr Photogr 1968; 44: 58-89
Gay BB Jr, Elsas LJ, Wyly JB, Pasquali M. Osteopathia striata
with cranial sclerosis. Pediatr Radiol 1994; 24: 56–60
Harris HA. The growth of the long bones in childhood with
special reference to certain bony striations of the metaphysis and to the role of the vitamins. Arch Intern Med 1926;
38: 785–94
Langer LO, Beals RK, Scott CI. Sponastrime dysplasia: diagnostic criteria based on five new and six previously published
cases. Pediatr Radiol 1997; 27: 409–14
McAlister WH, Herman TE. Osteochondrodysplasias, dysostoses, chromosomal aberrations, mucopolysaccharidoses,
and mucolipidoses. In: Resnick D (ed.) Diagnosis of bone
and joint disorders. W. B. Saunders Company, Philadelphia,
1995 (3rd ed.), pp. 4163–244
McAlister WH, Lester PD. Diseases of the adrenal. Med Radiogr Photogr 1971; 47: 62–81
Nixon GW, Gwinn JL. The roentgen manifestations of
leukemia in infancy. Radiology 1973; 107: 603–9
356
Chapter 5 · Long Bones
Ogden JA. Growth slowdown and arrest lines. J Pediatr Orthop
1984; 4: 409–15
Park EA, Richter CP. Transverse lines in bone: the mechanism
of their development. Bull Johns Hopkins Hosp 1953; 93:
234–48
Pease CN, Newton GB. Metaphyseal dysplasia due to lead poisoning. Radiology 1962; 79: 233–40
Resnick D. Hypervitaminosis and hypovitaminosis. In: Resnick D (ed.) Diagnosis of bone and joint disorders. W.B.
Saunders Company, Philadelphia, 1995 (3rd ed.), pp.
3343–64
Resnick D, Niwayama G. Osteoporosis. In: Resnick D (ed.) Diagnosis of bone and joint disorders. W.B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 1783–853
Van Slyck EJ. The bony changes in malignant hematologic disease. Orthop Clin North Am 1972; 3: 733–4
Verloes A, Misson JP, Dubru JM, Jamblin P, Le Merrer M. Heterogeneity of SPONASTRIME dysplasia: delineation of a
variant form with severe mental retardation. Clin Dysmorph 1995; 4: 208–15
Wihlborg C, Babyn P, Ranson M, Laxer R. Radiologic mimics of
juvenile rheumatoid arthritis. Pediatr Radiol 2001; 31:
315–26
Winter RM, Crawfurd MD, Meire HB, Mitchell N. Osteopathia
striata with cranial sclerosis: highly variable expression
within a family including cleft palate in two neonatal cases.
Clin Genet 1980; 18: 462–74
Young LW, Lachman RS. Asynchronous asymmetric form of
heterogeneous osteopetrosis: initial case expanded and a
new case. Pediatr Radiol 2001; 31: 48–53
Fig. 5.56. X-linked hypophosphatemic rickets in a 2-year-old
boy. There is poor mineralization of the metaphyseal regions,
with a coarse (malacic) bone texture. The metaphyses show
mild fraying, cupping, and widening
Irregular Metaphyses
䉴 [Coarse, frayed, disorganized metaphyses
with edge indistinctness]
As anticipated above in the section “Metaphyseal
Cupping,” marked changes around the metaphyses,
including undermineralization of the provisional
zone, widening, cupping, and fraying, are characteristic features in rickets, X-linked hypophosphatemia
(familial vitamin D-resistant rickets, OMIM 307800)
(Fig. 5.56), and hypophosphatasia (OMIM 241500,
146300) (Fallon et al. 1984). Extensive metaphyseal
changes occur in the conditions grouped together
under the designation of metaphyseal chondrodysplasia. Histological findings are nonspecific and similar in all the metaphyseal chondrodysplasias, consisting in disorganized arrangement of the cartilage
cells in the growth plate with retarded endochondral
bone formation. In metaphyseal chondrodysplasia,
Jansen type (OMIM 156400), a rare autosomal dominant dwarfing disorder with joint swelling and bowing of legs and forearms, metaphyseal changes vary
according to the patient’s age. In infancy, mild metaphyseal irregularities in the short and long tubular
bones are seen. In childhood, severe metaphyseal
a
b
Fig. 5.57 a, b. Metaphyseal chondrodysplasia, Jansen type in a
boy. a In the neonatal period only mild metaphyseal irregularities are seen. The bones are undermineralized. b In images
taken when the boy was 7 years old severe metaphyseal
changes have developed, with metaphyseal widening, cupping,
and a typical coarse pattern of dense areas interspersed with
areas of increased radiolucency. The epiphyses are grossly normal, and are widely separated from corresponding metaphyses. (From Giedion 1994)
Metaphyseal Abnormalities
Fig. 5.58. Metaphyseal chondrodysplasia, Schmid type in a
3-year-old girl. The femurs are bowed, with relatively dense
diaphyses. The metaphyses are irregularly ossified, with fraying and splaying. The growth plates are wide, with normal epiphyses
cupping, irregular calcification, and fragmentation
occur (Fig. 5.57a,b). Scattered foci of irregular calcification are interspersed with radiolucent areas of
unossified cartilage. In adults, most of the roentgenographic changes about the metaphyses improve,
while leaving severely short and bowed limbs with
expanded metaphyses (Charrow and Pznanski 1984).
The autosomal dominant metaphyseal chondrodysplasia, Schmid type (OMIM 156500) usually manifests after infancy. The radiographic pattern, which is
remarkably similar to that in X-linked hypophosphatemic rickets, includes diffuse metaphyseal flaring, irregularity, and growth plate widening, which
are most severe in the knees (Gellis et al. 1980)
(Fig. 5.58). Unlike the pattern in vitamin-D resistant
rickets, however, the metaphyses are well mineralized. The hands are not affected, while the vertebrae
are only occasionally involved. [The observation of a
possible spinal involvement in metaphyseal chon-
357
drodysplasia has led Savarirayan et al. (2000) to conclude that Schmid metaphyseal chondrodysplasia
and spondylometaphyseal dysplasia, Japanese type,
are identical conditions.] The autosomal recessive
metaphyseal chondrodysplasia, McKusick type (cartilage hair hypoplasia, OMIM 250250) is characterized
by striking metaphyseal abnormalities in the tubular
bones, most prominent at the knees, with flaring,
cupping, scalloping, marginal serration, and fragmentation. Irregular cyst-like radiolucencies extending from the metaphyses into the diaphyses are
also present. Epiphyses are only mildly affected
(McKusick et al. 1965). Greater involvement of the
metaphyses at the knees and less prominent coxa
vara and bowed legs are useful radiologic criteria
that can be applied to differentiate McKusick type
from Schmid type metaphyseal chondrodysplasia.
Moreover, the metaphyses of the metatarsals, metacarpals, and phalanges are also affected. Metaphyseal
chondrodysplasia, Shwachman-Diamond type (OMIM
260400) is a short-limbed dwarfism of autosomal recessive inheritance, which is characterized by failure
to thrive, malabsorption related to exocrine pancreatic insufficiency, blood cell diminution (leukopenia, neutropenia, thrombocytopenia), recurrent
infections, and ectodermal dysplasia. Metaphyseal
changes are discrete, predominate at the levels of the
hips and knees, and consist of alternating sclerotic
and radiolucent areas, which may eventually appear
radiographically as metaphyseal vertical striations
(McLennan and Steinbach 1974). Metaphyseal anadysplasia (OMIM 309645) is another metaphyseal
bone dysplasia, characterized by early-onset, severe
metaphyseal changes that regress spontaneously over
time with complete restoration of the normal bony
structure (Wiedemann and Spranger 1970; Maroteaux et al. 1991). The favorable course is the distinguishing feature of this disorder. Patients’ final height
is normal. The metaphyseal alterations include irregularities, widening, and marginal blurring and are
most prominent in the proximal femurs (Fig. 5.59a,b).
The long bones of the upper limbs are far less
commonly involved. The epiphyses are spared.
Most of those affected are male. The inheritance
pattern is unknown, X-linked dominant or autosomal dominant transmission being likely (Slama et
al. 1999). Severe combined immunodeficiency (SCID)
with adenosine deaminase (ADA) deficiency (OMIM
102700) may show mild metaphyseal changes, including flaring and irregularities, sometimes in the shape
of lateral spurs. Histological findings include lack of
organized cartilage columnar formation, large lacunas with hypertrophied cells, and lack of trabecular
358
Chapter 5 · Long Bones
a
Fig. 5.60. Osteoglophonic dysplasia in an 11-year-old boy. Note
multiple, large metaphyseal nonossifying fibromata extending
into the diaphysis. The epiphyses are small and flattened. The
knee joint space is widened. (From Azouz et al. 1997)
b
Fig. 5.59 a, b. Metaphyseal anadysplasia in a 4 1/2-month-old
girl. a Note severe metaphyseal alterations with widened, irregularly sclerotic proximal femoral metaphyses, and markedly
short femoral necks. b Similar metaphyseal abnormalities are
evident at the knee and ankle. There is also mild bowing of the
long bones. These abnormalities had disappeared completely
on follow-up X-rays (not shown). (From Slama et al. 1999)
formation. These changes are distinctly different
from those observed in the metaphyseal chondrodysplasias or in other chondrodystrophies (Cederbaum
et al. 1976). The association of metaphyseal irregular-
ities and flaring, most prominent in the forearm,
thickened dorsum sellae, and wedged vertebrae delineates the condition known as metaphyseal-sella
turcica dysplasia (Rosenbaum and Lohr 1986). Varying degrees of metaphyseal and spinal involvement,
from minimal to severe, are seen in spondylometaphyseal dysplasia, Kozlowski type (OMIM 184252).
Changes include metaphyseal irregularity, widening,
and sclerosis, and platyspondyly with spinal malalignment (Kozlowski et al. 1980). Among the several
types of spondyloepimetaphyseal dysplasias the
autosomal recessive spondyloepimetaphyseal dysplasia, Irapa type (OMIM 271650), displays widespread
metaphyseal irregularities and widening, but the
proximal femur and distal humerus are most prominently affected. Epiphyses appear later than expected
and are small and irregular. Platyspondyly is generalized. Early-onset osteoarthritic changes of severe
degree are seen around the major joints (Hernandez
et al. 1980). In spondyloepimetaphyseal dysplasia,
Strudwick type (OMIM 184250), changes in infancy
are mainly those related to the epiphyseal component
of dysplasia. Metaphyseal changes, which are less obvious in infancy, become more prominent by early
childhood, with irregularities, fragmentation, and
alternating sclerotic and radiolucent areas (mottling
or dappling). The distal ulna is more severely affected than the radius, and the proximal fibula more than
the tibia. Severe platyspondyly can be observed at all
ages (Anderson et al. 1982). A peculiar type of metaphyseal involvement is encountered in osteoglophonic dysplasia (OMIM 166250), a dwarfing disorder of
Metaphyseal Abnormalities
a
b
c
359
d
Fig. 5.61 a–d. Spondyloenchondromatosis. a In a 2-year-old
girl spondyloenchondromatosis associated with D-2-hydroxyglutaric aciduria. Note gross metaphyseal abnormalities, with
splaying columns of ossification alternating with islands of
unossified cartilage resembling enchondromata. b–d. A boy
examined at b 1 1/2 years, c 2 1/2 years, and d 9 years of age:
there are enchondromas in the distal femoral and proximal
fibular metaphyses, which move further into the diaphyses and
become sclerotic at between the ages of 1 1/2 and 2 1/2 years.
By 9 years of age, the enchondromas have disappeared, leaving
marked striation of the femoral and tibial metaphyses. [From
Talkhani et al. 2000 (a) and Uhlmann et al. 1998 (b–d)]
the rhizomelic type that is characterized by cloverleaf deformity of the skull, frontal bossing, hypertelorism, craniostenosis, fibrous dysplasia of the
mandibular ramus, platyspondyly, and gross dysplastic changes in the metaphyses, with irregular areas of
radiolucency (fibrous cortical defects and nonossifying fibromata) (Beighton et al. 1980) (Fig. 5.60). Radiolucent defects in the metaphyses, extending into the
diaphyses, are also seen in enchondromatosis (Ollier
disease, OMIM 166000). These radiolucent areas can
be elongated, oval, or round, and they correspond to
masses of unossified cartilage. The distribution can
be either unilateral or bilateral, and the bones involved are sometimes markedly short. Adjacent epiphyses are usually hypoplastic and irregular (Mainzer et al. 1971). Enchondromatous changes in the
metaphyses of the long and flat bones are also found
in spondylo-enchondro-dysplasia (OMIM 271550), a
very rare autosomal recessive disorder in which
short stature and severe platyspondyly with endplate irregularities are further features (Schnorr et al.
1976). The enchondroma-like lesions sometimes disappear with time (Uhlmann et al. 1998) (Fig. 5.61a–d).
Patients undergoing iron chelation therapy with
deferoxamine may show metaphyseal changes, especially about the knees and wrists, consisting in meta-
physeal widening, cupping, fraying, and cystic
changes of the subchondral bone.
Radiographic Synopsis
AP and lateral projections
1. Widened, cupped, frayed metaphyses; poor mineralization (rickets, X-linked hypophosphatemia;
hypophosphatasia tarda)
2. Severe metaphyseal changes (in children), with
fragmentation and irregular calcification; short,
bowed limbs with expanded metaphyses (in adults)
(metaphyseal chondrodysplasia, Jansen type)
3. As in hypophosphatemic rickets, but with preserved mineralization (metaphyseal chondrodysplasia, Schmid type)
4. Cyst-like meta-diaphyseal radiolucencies (metaphyseal chondrodysplasia, McKusick type; osteoglophonic dysplasia; enchondromatosis; spondyloenchondromatosis)
5. Mild metaphyseal changes; lateral spurs (SCID
with ADA deficiency)
6. Metaphyseal changes; platyspondyly (spondylometaphyseal dysplasia, Kozlowski type)
7. Dappled metaphyses; epiphyseal abnormalities;
early-onset osteoarthritis; platyspondyly (spondyloepimetaphyseal dysplasias)
360
Chapter 5 · Long Bones
Associations
• Battered child syndrome
• Drugs (deferoxamine)
• Enchondromatosis (Ollier)
• Fracture
• Hyperparathyroidism
• Hypophosphatasia
• Hypophosphatemia
• Immunodeficiency, severe combined (SCID)
with ADA deficiency
• Infection
• Kniest dysplasia
• Metaphyseal chondrodysplasias (Schmid, Jansen,
McKusick, Shwachman-Diamond, with exocrine
pancreatic insufficiency)
• Metaphyseal-sella turcica dysplasia (Rosenberg)
• Osteoglophonic dysplasia
• Osteopetrosis
• Parastremmatic dwarfism
• Pseudoachondroplasia
• Rickets
• Short rib-polydactyly syndrome type 1
• Spondyloenchondromatosis
• Spondyloepimetaphyseal dysplasias
(Irapa, Strudwick)
• Spondylometaphyseal dysplasia (Kozlowski)
• Vitamin A intoxication
References
Anderson CE, Sillence DO, Lachman RS, Toomey K, Bull M,
Dorst J, Rimoin DL. Spondylometepiphyseal dysplasia,
Strudwick type. Am J Med Genet 1982; 13: 243–56
Azouz EM, Kozlowski K. Osteoglophonic dysplasia: appearance and progression of multiple nonossifying fibromata.
Pediatr Radiol 1997; 27: 75–8
Beighton P, Cremin BJ, Kozlowski K. Osteoglophonic
dwarfism. Pediatr Radiol 1980; 10: 46–50
Cederbaum SD, Kaitila I, Rimoin DL, Stiehm ER. The chondroosseous dysplasia of adenosine deaminase deficiency with
severe combined immunodeficiency. J Pediatr 1976; 89:
737–42
Charrow J, Poznanski AK. The Jansen type of metaphyseal
chondrodysplasia: confirmation of dominant inheritance
and review of radiographic manifestations in the newborn
and adult. Am J Med Genet 1984; 18: 321–7
Fallon MD, Teitelbaum SL, Weinstein RS, Goldfischer S, Brown
DM, Whyte MP. Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. Medicine 1984; 63: 12–24
Gellis SS, Feingold M, Pavone L, Mollica F, Sorge G. Picture of
the month. Metaphyseal chondrodysplasia, Schmid type.
Am J Dis Child 1980; 134: 699–700
Hernandez A, Ramirez ML, Nazara Z, Ocampo R, Ibarra B,
Cantu JM. Autosomal recessive spondylo-epi-metaphyseal
dysplasia (Irapa type) in a Mexican family: delineation of
the syndrome. Am J Med Genet 1980; 5: 179–88
Kozlowski K, Cremin B, Beighton P. Variability of spondylometaphyseal dysplasia, common type. Radiol Diagn 1980;
21: 682–6
Mainzer F, Minagi H, Steinbach HL. The variable manifestations of multiple enchondromatosis. Radiology 1971; 99:
377–88
Maroteaux P, Verloes A, Stanescu V, Stanescu R. Metaphyseal
anadysplasia: a metaphyseal dysplasia of early onset with
radiological regression and benign course.Am J Med Genet
1991; 39: 4–10
McKusick VA, Eldridge R, Hostetler JA, Egeland JA, Ruangwit
U. Dwarfism in the Amish. II. Cartilage-hair hypoplasia.
Bull Johns Hopkins Hosp 1965; 116: 285–326
McLennan TW, Steinbach HL. Schwachman’s syndrome: the
broad spectrum of bony abnormalities. Radiology 1974;
112: 167–73
Rosenberg E, Lohr H. A new hereditary bone dysplasia with
characteristic bowing and thickening of the distal ulna. Eur
J Pediatr 1986; 145: 40–5
Savarirayan R, Cormier-Daire V, Lachman RS, Rimoin DL.
Schmid type metaphyseal chondrodysplasia: a spondylometaphyseal dysplasia identical to the “Japanese” type.
Pediatr Radiol 2000; 30: 460–3
Schorr S, Legum C, Ochshorn M. Spondyloenchondrodysplasia. Enchondromatomosis with severe platyspondyly in two
brothers. Radiology 1976; 118: 133–9
Slama M, Mathieu M, Dehouck I, al Hosri J, Vanthournout I,
Baratte B, Grumbach Y. Metaphyseal anadysplasia in two
sisters. Pediatr Radiol 1999; 29: 372–5
Talkhani IS, Saklatvala J, Dwyer J. D-2-hydroxyglutaric
aciduria in association with spondyloenchondromatosis.
Skeletal Radiol 2000; 29: 289–92
Uhlmann D, Rupprecht E, Keller E, Hormann D. Spondyloenchondrodysplasia: several phenotypes – the same syndrome. Pediatr Radiol 1998; 28: 617–21
Wiedemann HR, Spranger J. Chondrodysplasia metaphysaria
(Dysostosis metaphysaria) – ein neuer Typ? Z Kinderheilkd
1970; 108: 171–86