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DOI 10.1515/crpm-2012-0028 Case Rep. Perinat. Med. 2012; 1(1-2): 99–102
Philline Peppermint D. Tanchi*, Liza Kathleen Edmonds and Tieh Hee Hai Guan Koh
Carey-Fineman-Ziter syndrome: a spectrum of
Abstract: Carey-Fineman-Ziter syndrome is characterized
by facial diplegia with an ophthalmoplegia comprising
the Moebius sequence, Pierre Robin sequence with micrognathia, short stature, postnatal-onset microcephaly,
hypotonia and muscular hypoplasia, extensive brainstem involvement, and pontine hypoplasia. We report a
38-week-gestation infant with features consistent with
Carey-Fineman-Ziter syndrome but with phenotypical
features that have not previously been described. The
infant had severe hypoplasia of the pons and cerebellum,
seizures, hypotonia, ophthalmoplegia, downslanting palpebral fissures, tongue hypoplasia, micrognathia, and
facial diplegia. The karyotype was normal. Of note, there
was a focal contour abnormality in the anterior two-thirds
of the tongue, which necessitated tracheostomy on the
third day of life to maintain the airway, and a well-circumscribed mass on both sides of the chest. These features
have not been previously found to be associated with this
syndrome, and the clinical significance is unknown. Case
reports of rare disorders give significant information on
the diagnosis, description, and evolving phenotype of
rare syndromes.
Keywords: Carey-Fineman-Ziter syndrome;
sequence; Robin sequence; tongue anomaly.
*Corresponding author: Dr. Philline Peppermint D. Tanchi, Registrar,
Neonatal Unit, Townsville Hospital, 100 Angus Smith Drive, Douglas,
QLD 4814, Queensland, Australia, E-mail: [email protected]
Liza Kathleen Edmonds and Tieh Hee Hai Guan Koh: Neonatal Unit,
The Townsville Hospital, Douglas, Queensland, Australia
Carey-Fineman-Ziter syndrome is a rare syndrome initially
described in 1982 [1]. It is characterized by facial diplegia with an ophthalmoplegia comprising the Moebius
sequence, facial anomalies, the Pierre Robin sequence
with micrognathia, short stature, postnatal-onset microcephaly, hypotonia and muscular hypoplasia, failure
to thrive, and delayed motor milestones. Other reports
have described similar characteristics and also relative
macrocephaly and downslanting palpebral fissures [2, 5,
6]. Later reports describe extensive brainstem involvement
and pontine hypoplasia [4]. Ryan et al. [5] described a
case with scoliosis, talipes equinovarus, and non-specific
primary myopathy as part of the syndrome. Dufke et al.
[3] reported similar features associated with intermittent
episodes of hypertension of unknown origin, Poland
sequence (unilateral aplasia of the pectoralis muscle),
and laryngostenosis. We describe additional features not
previously described, which may suggest that this syndrome manifests as a spectrum of presentations.
Clinical report
The female infant was born at 38 weeks’ gestation by emergency cesarean section due to fetal distress, presence of
meconium liquor, and antepartum hemorrhage. She was
born with Apgars of 4 at 1 min and 9 at 5 min. The birth
weight was 3080 g (45th centile), length was 49 cm (40th
centile), and head circumference was 33 cm (20th centile).
The mother was gravida 5, para 3, with a history of significant alcohol ingestion in the first trimester and a previous
pregnancy complicated by an anencephalic fetus. Maternal
serology was unremarkable, except for a history of Candida
and Trichomonas. An ultrasound at 30 weeks found no
gross fetal abnormalities and normal liquor volume.
Clinically, the infant was found to have Moebius
sequence (ophthalmoplegia, facial diplegia, downwardslanting palpebral fissures) and Pierre Robin sequence
(micrognathia, small mouth opening). In addition to these
features, she also had a globular mass at the back of the
tongue, fusion of the anterior margins of the tongue, gum
comprising the floor of the mouth, and subcutaneous
rubbery lesions (2.3 × 1.8 cm) below the left nipple.
Soon after birth, she developed respiratory distress
requiring continuous positive airway pressure. She later
had significant apnoeic and cyanotic episodes necessitating intubation. However, due to the lump at the back of
her throat and recurrent upper airway obstruction, she
required a tracheostomy on day 3 of life to maintain her
She was also found to be hypotonic, with periodic
jerking and stiffening of limbs, and with subclinical
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100 Tanchi et al., Carey-Fineman-Ziter syndrome
Figure 1 MRI demonstrating cerebellar and pontine hypoplasia.
Figure 3 MRI demonstrating chest wall lesion
seizures on amplitude-integrated electroencephalography requiring treatment with phenobarbitone. She had a
gag but no swallow or cough reflex, and was on gavage
feeding. Magnetic resonance imaging revealed severe
hypoplasia of the pons and cerebellum. The cerebrum
was described to have normal sulcation with prominence
of sulcal spaces suggestive of mild cerebral shrinkage
(Figure 1). There was micrognathia with microglossia
and an abnormal contour of the anterior two-thirds of
the tongue, which may represent a dysplastic mass lesion
(Figure 2). There was a well-circumscribed lesion on both
sides of the anterior chest, which may be either mammary
tissue or soft tissue lesions of indeterminate etiology.
Chromosome analysis and fluorescence in situ hybridization showed a normal female karyotype, and no other
abnormalities were detected (Figures 3–5). A microarray
Figure 2 MRI head demonstrating cerebellar and pontine
Figure 4 MRI demonstrating tongue abnormalities.
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Tanchi et al., Carey-Fineman-Ziter syndrome 101
Figure 5 Photograph demonstrating tongue anomaly and
comparative genomic hybridization was not performed, as
this was not widely available at the time of this case.
Despite having a tracheostomy, she had severe
hypoventilation with persistent apnoeic episodes requiring
resuscitation. Owing to severe neurologic impairment and
lack of progress, it was decided to suspend intensive care, and
she died on day 25 of life. A postmortem was not performed.
Carey-Fineman-Ziter syndrome has been described in
the literature with a spectrum of presentations, which
mainly include the Moebius sequence and the Pierre
Robin sequence [1–6]. There have also been reports of
brain abnormalities [4], and consistent with this, we
report an infant with severe hypoplasia of the pons and
the cerebellum. In addition to these features, our patient
had new features not previously reported. There was a
focal contour abnormality in the anterior two-thirds of the
tongue necessitating tracheostomy early in life to maintain airway. We hypothesize that the tongue mass may
be a variation in the manifestations of the Pierre Robin
sequence. There was also a well-circumscribed lesion on
both sides of the anterior chest, not previously reported
with this syndrome. These may be mammary tissue or a
soft tissue lesion, the significance and etiology of which is
unknown. It can be postulated that this is a manifestation
of the musculoskeletal involvement previously described
in this syndrome.
There are still no known genetic testing or laboratory tests specific for Carey-Fineman-Ziter syndrome, and
muscle biopsy of previous cases revealed mild non-specific myopathic changes [1–3, 6]. Inheritance is believed
to be autosomal recessive, as sibling pairs have been
reported in the literature [1, 2, 5, 7]. On the basis of previous findings in the literature, the major criteria for CareyFineman-Ziter syndrome include the Moebius and Robin
sequences, hypotonia, facial anomalies, congenital nonprogressive myopathy, and delayed motor development
[3]. These features were present in our patient, although
myopathy and motor development was not possible to
determine, as our patient did not survive. In addition to
this, we report an abnormal contour of the tongue and
masses on both sides of the chest, a feature not previously
associated with this syndrome.
The original siblings reported by Carey et al. [1, 2]
who survived to adulthood had, in contrast to our case,
normal computed tomography head scans and did not
require mechanical ventilation. Their conditions were significantly different and quality of life was better achieved.
Verloes and colleagues [7] reviewed nine unrelated cases
of which two patients had severe hypoventilation and
severe brainstem abnormalities and both did not survive.
For rare syndromes, reports of individual clinical cases
may offer vital information in defining the spectrum of a specific clinical entity. It may be that this syndrome involves a
spectrum of abnormalities and phenotypes that will become
more apparent over time as more cases are reported.
Received May 7, 2012. Accepted October 15, 2012. Previously
published online November 19, 2012.
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original siblings and comments on pathogenesis (Editorial
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consequence of malformation, dysplasia and neuromuscular
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[3] Dufke A, Riethmuller J, Enders H. Severe congenital myopathy
with Mobius, Robin and Poland sequences: new aspects of the
Carey-Fineman-Ziter syndrome. Am J Med Genet. 2004;127A:291–3.
[4] Maheshwari A, Calhoun DA, Lacson A, Pereda L, Nelson RM,
Saste MD, et al. Pontine hypoplasia in Carey-Fineman-Ziter (CFZ)
syndrome. Am J Med Genet. 2004;127A:288–90.
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102 Tanchi et al., Carey-Fineman-Ziter syndrome
[5] Ryan A, Marshall T, FitzPatrick DR. Carey-Fineman-Ziter (CFZ)
syndrome: report on affected sibs. Am J Med Genet. 1999;82:110–3.
[6] Schimke RN, Collins DL, Hiebert JM. Congenital nonprogressive myopathy with Mobius and Robin sequence – the
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Genet. 1993;46:721–3.
[7] Verloes A, Bitoun P, Heuskin A, Amrom D, Van de
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The authors stated that there are no conflicts of interest regarding
the publication of this article.
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