Cat Eye Syndrome
Cat-eye syndrome is a clinically recognizable congenital
malformation syndrome consisting primarily of colobomas,
anal anomalies, pre-auricular anomalies, cardiac and renal
defects, and mild to moderate mental retardation. The name
“cat eye” was introduced because of iris colobomas resembling
the pupils of the cat.
GENETICS/BASIC DEFECTS
1. Historic background
a. In 1965, an extra bisatellited marker chromosome was
described in patients with cat-eye syndrome phenotype
b. Later in 1981, the marker was determined to be an
inverted dicentric duplication of a part of chromosome 22 [inv dup(22)(pter→q11::q11→pter)]
2. Molecular and cytogenetic bases
a. Associated with the presence of three copies (trisomy) or four copies (tetrasomy) of a segment of
chromosome22q11.2, usually in the form of a bisatellited, isodicentric supernumerary chromosome
b. Formation of transient or unstable dic r(22) during
early fetal development, which subsequently are lost
from most cells, resulting in cat eye syndrome features
c. The minimal common duplication required to produce features of cat eye syndrome (the cat eye syndrome critical region): defined by the dic r(22)
patient, breakpoints between proximal locus ATP6E
and distal locus D22S57, and covering approximately
2 Mb of 22q11.2
d. Maternal origin of the supernumerary chromosome in
cases studied
e. Direct correlations between the extent of duplicated
chromosome 22 material and the severity of the cat
eye syndrome remain difficult.
f. Human homolog of insect-derived growth factor,
CECR1: a candidate gene for features of cat-eye
syndrome
CLINICAL FEATURES
1. Marked phenotypic variability
2. Major features
a. Preauricular skin tags and/or pits: most consistent
features
b. Ocular coloboma
c. Congenital heart defect
i. Ventricular septal defect
ii. Total anomalous pulmonary venous connection
iii. Atrial septal defect
iv. Patent ductus arteriosus
v. Pulmonary stenosis
vi. Aortic malformation
vii. Tricuspid atresia
viii. Hypoplastic left heart syndrome
136
d. Anorectal malformations
i. Anal atresia or imperforate anus
ii. Anal stenosis
iii. Anorectal atresia
iv. Ectopic anus
v. Associated rectal fistulas
e. Urogenital malformations
i. Male external genital malformation
ii. Renal agenesis/hypoplasia
iii. Hydro(uretero) nephrosis
iv. Vesicoureteral reflux
v. Female genital malformation
vi. Renal dysplasia or polycystic kidney
vii. Bladder defects
viii. Renal cystic malformation
ix. Ectopic/horseshoe kidney
3. Minor features
a. Craniofacial abnormalities
i. Microcephaly
ii. Ocular abnormalities
a) Downslanting palpebral fissures
b) Hypertelorism
c) Ocular motility defect
d) Epicanthal folds
e) Microphthalmia
iii. Oral abnormalities
a) Micrognathia
b) Cleft palate or absent uvula
iv. Low-set or dysplastic ears
b. Skeletal abnormalities
i. Arm or hand deformity
ii. Leg or foot deformity
iii. Scoliosis or chest deformity
iv. Vertebral anomaly
v. Congenital dislocation of the hip
vi. Rib or sternal anomaly
c. Abdominal abnormalities
i. Umbilical hernia
ii. Malrotation of the gut
iii. Hirschsprung or megacolon
iv. Biliary atresia or choledochal cyst
v. Volvulus
vi. Meckel diverticulum
4. Neurodevelopmental outcome
a. Growth and development
i. Short stature
ii. Mental development: markedly variable
a) Normal-borderline normal
b) Mild-moderate retardation
c) Severe mental retardation
b. Neurological abnormalities
i. Dysregulation of muscle tone
ii. Visual defect
CAT EYE SYNDROME
iii.
iv.
v.
vi.
vii.
viii.
ix.
x.
xi.
Hearing impairment
Ventricular dilatation
Abnormal slow EEG
Seizures
Spasticity
Cerebral or cerebellar atrophy
Hyperactive behavior
Ataxia
Facial nerve palsy
DIAGNOSTIC INVESTIGATIONS
1. Chromosome analysis from blood and other tissues
a. Conventional
b. FISH
2. Radiography for limb defect
3. Echocardiography for congenital heart defects
4. Renal ultrasonography for renal anomalies
5. Developmental evaluation
GENETIC COUNSELING
1. Recurrence risk
a. Patient’s sib: a small recurrence risk because of possible presence of germline mosaicism
b. Patient’s offspring
i. Patients with an inv dup(22): 50%
ii. Patients with mosaic form of an inv dup(22):
lower than 50%, depends on the percentage of
the marker chromosomes
2. Prenatal diagnosis by amniocentesis or CVS
a. Presence of a bisatellited, dicentric supernumerary
chromosome
b. FISH with a chromosome 22-specific cosmid probe
to identify chromosome 22
3. Management
a. Supportive
b. Surgery
i. Congenital heart defect
ii. Anorectal anomalies
iii. Urogenital anomalies
iv. Gastrointestinal anomalies
v. Skeletal anomalies
c. Potential anesthetic risks
i. Potential difficult airway management
ii. Congenital heart disease
iii. Renal and hepatic dysfunction
REFERENCES
Beeser SL, Donnenfeld AE, Miller RC, et al.: Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in
situ hybridization. Prenat Diagn 14:1029–1034, 1994.
Berends MJ, Tan-Sindhunata G, Leegte B, et al.: Phenotypic variability of CatEye syndrome. Genet Couns 12:23–34, 2001.
Bofinger MK ,Soukup SW: Cat eye syndrome. Partial trisomy 22 due to
translocation in the mother. Am J Dis Child 131:893–897, 1977.
Bühler EM, Mehes K, Muller H, et al.: Cat-eye syndrome, a partial trisomy 22.
Humangenetik 15:150–162, 1972.
Cory CC ,Jamison DL: The cat eye syndrome. Arch Ophthalmol 92:259–262,
1974.
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Crolla JA, Howard P, Mitchell C, et al.: A molecular and FISH approach to
determining karyotype and phenotype correlations in six patients with
supernumerary marker (22) chromosomes. Am J Med Genet 72:440–447,
1997.
Devavaram P, Seefelder C ,Lillehei CW: Anaesthetic management of Cat Eye
Syndrome. Paediatr Anaesth 11:746–748, 2001.
Duncan AM, Rosenfeld W ,Verma RS: Re-evaluation of the supernumerary
chromosome in an individual with cat eye syndrome. Am J Med Genet
27:225–227, 1987.
El-Shanti H, Hulseberg D, Murray JC, et al.: A three generation minute supernumerary ring 22: association with cat eye syndrome. Am J Hum Genet
53(suppl):A126, 1993.
Freedom RM ,Gerald PS: Congenital cardiac disease and the “cat eye” syndrome. Am J Dis Child 126:16–18, 1973.
Guanti G: The aetiology of the cat eye syndrome reconsidered. J Med Genet
18:108–118, 1981.
Hoo JJ: DA/DAPI pattern of marker chromosome: cytogenetics of cat eye syndrome. Clin Genet 29:265–267, 1986.
Hoo JJ, Robertson A, Fowlow SB, et al.: Inverted duplication of 22pter—
q11.21 in cat-eye syndrome. Am J Med Genet 24:543–545, 1986.
Hsu LYF, Hirschhorn K: The trisomy 22 syndrome and the cat eye syndrome.
In Yunis JJ (ed): New Chromosomal Syndromes. New York, Academic
Press, 1977, 339–368.
Johnson A, Minoshima S, Asakawa S, et al.: A 1.5-Mb contig within the cat eye
syndrome critical region at human chromosome 22q11.2. Genomics
57:306–309, 1999.
Kolvraa S, Koch J, Gregersen N, et al.: Application of fluorescence in situ
hybridization techniques in clinical genetics: use of two alphoid repeat
probes detecting the centromeres of chromosomes 13 and 21 or chromosome 14 and 22, respectively. [erratum appears in Clin Genet 40:474 –475,
1991]. Clin Genet 39:278–286, 1991.
Liehr T, Pfeiffer RA ,Trautmann U: Typical and partial cat eye syndrome: identification of the marker chromosome by FISH. Clin Genet 42:91–96,
1992.
Magenis RE, Sheehy RR, Brown MG, et al.: Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in
situ hybridization analysis. Am J Med Genet 29:9–19, 1988.
McDermid HE, Duncan AM, Brasch KR, et al.: Characterization of the supernumerary chromosome in cat eye syndrome. Science 232:646–648, 1986.
McTaggart KE, Budarf ML, Driscoll DA, et al.: Cat eye syndrome chromosome breakpoint clustering: identification of two intervals also associated
with 22q11 deletion syndrome breakpoints. Cytogenet Cell Genet 81:
222–228, 1998.
Mears AJ, Duncan AM, Budarf ML, et al.: Molecular characterization of the
marker chromosome associated with cat eye syndrome. Am J Hum Genet
55:134–142, 1994.
Mears AJ, el-Shanti H, Murray JC, et al.: Minute supernumerary ring chromosome 22 associated with cat eye syndrome: further delineation of the critical region. Am J Hum Genet 57:667–673, 1995.
Reeser SL, Donnenfeld AE, Miller RC, et al.: Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in
situ hybridization. Prenat Diagn 14:1029–1034, 1994.
Riazi MA, Brinkman-Mills P, Nguyen T, et al.: The human homolog of insectderived growth factor, CECR1, is a candidate gene for features of cat eye
syndrome. Genomics 64:277–285, 2000.
Rosias PR, Sijstermans JM, Theunissen PM, et al.: Phenotypic variability of
the cat eye syndrome. Case report and review of the literature. Genet
Couns 12:273–282, 2001.
Schachenmann G, Schmid W, Fraccaro M, et al.: Chromosomes in coloboma
and anal atresia. Lancet 290, 1965.
Schinzel A, Schmid W, Fraccaro M, et al.: The “cat eye syndrome”: Dicentric
small marker chromosome probably derived from a N° 22 (tetrasomy
22pter ≥ q11) associated with a characteristic phenotype. Report of 11
patients and delineation of the clinical picture. Hum Genet 57:148–158,
1981.
Urioste M, Visedo G, Sanchis A, et al.: Dynamic mosaicism involving an unstable supernumerary der(22) chromosome in cat eye syndrome. Am J Med
Genet 49:77–82, 1994.
Wilson GN, Baker DL, Schau J, et al.: Cat eye syndrome owing to tetrasomy
22pter→q11. J Med Genet 21:60–63, 1984.
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CAT EYE SYNDROME
Fig. 1. A boy with cat eye syndrome showing ocular coloboma and
bilateral club hands with missing thumbs. The radiographs shows
bilateral radial aplasia/hypoplasia with missing thumbs. The patient
has a supernumerary marker chromosome 22, illustrated by the chromosome spread.