Prenatal and neonatal MR imaging findings in oral-facial-digital syndrome type VI.
ABSTRACT We report prenatal and neonatal neuroimaging findings in a case of oral-facial-digital syndrome type VI (OFDS VI). Prenatal MR imaging at 29 weeks' gestation showed hypoplastic cerebellar vermis and hemispheres, the molar tooth sign, and a hypothalamic hamartoma. Neonatal MR imaging confirmed these findings. The neonate developed breathing abnormalities and exhibited frontal bossing, multiple bucco-alveolar frenula, and postaxial hexadactyly of both hands. If the molar tooth sign and a hypothalamic hamartoma are present, prenatal diagnosis of OFDS VI is possible.
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ABSTRACT: Six children in an inbred isolate (a gypsy colony) were found to have a syndrome of reduplication of the big toes, supernumerary fingers on the hands, cleft lip/palate or lingual nodule, and somatic and psychomotor retardation. Other features sometimes present were absence of olfactory bulbs and tracts, cryptorchidism, inguinal hernia, and congenital heart disease. The disorder has overlapping features with several previously delineated syndromes, but is most similar to the anomalies of trisomy 13 Mand ohr's syndrome. Our patients had a normal karyotype. The mode of inheritance of this lethal genetic syndrome is probably autosomal recessive.Journal of Medical Genetics 05/1980; 17(2):119-22. · 5.70 Impact Factor
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ABSTRACT: Cerebellar anomalies are consistent findings in patients with the oral-facial-digital syndrome type VI (Váradi syndrome) in addition to variable facial and oral changes, and polysyndactyly of hands and feet. We report 3 unrelated patients with this entity who have a hypoplastic cerebellar vermis shown by magnetic resonance imaging (MRI), as well as clinical signs of cerebellar defect. Polydactyly of the hands is characterized by a central Y-shaped metacarpal. Clinically recurrent episodes of tachypnea and hyperpnea are remarkable. Postnatal growth is delayed with short stature in all 3 patients possibly due to growth hormone deficiency in one of them. In contrast to reported patients who are all severely mentally retarded, one of our patients is of normal intelligence. Type VI oral-facial-digital syndrome is an autosomal-recessive trait and may be detected prenatally.American Journal of Medical Genetics 04/1990; 35(3):360-9.
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ABSTRACT: Joubert syndrome (JS) and related disorders are characterized by the 'molar tooth sign' (cerebellar vermis hypoplasia and brainstem anomalies) on MRI, hypotonia, developmental delay, ataxia, irregular breathing pattern and abnormal eye movements. Combinations of additional features such as polydactyly, ocular coloboma, retinal dystrophy, renal disease, hepatic fibrosis, encephalocele, and other brain malformations define clinical sub-types. Recent identification of the NPHP1, AHI1, and CEP290 genes has started to reveal the molecular basis of JS, which may implicate the primary cilium in these disorders. Additional genes remain to be identified.European Journal of HumanGenetics 06/2007; 15(5):511-21. · 4.32 Impact Factor
Prenatal and Neonatal MR Imaging Findings in
Oral-Facial-Digital Syndrome Type VI
SUMMARY: We report prenatal and neonatal neuroimaging findings in a case of oral-facial-digital
syndrome type VI (OFDS VI). Prenatal MR imaging at 29 weeks’ gestation showed hypoplastic
cerebellar vermis and hemispheres, the molar tooth sign, and a hypothalamic hamartoma. Neonatal
MR imaging confirmed these findings. The neonate developed breathing abnormalities and exhibited
frontal bossing, multiple bucco-alveolar frenula, and postaxial hexadactyly of both hands. If the molar
tooth sign and a hypothalamic hamartoma are present, prenatal diagnosis of OFDS VI is possible.
orders (JSRD),3whereof less than 40 cases have been reported.
The genetic basis remains unknown. JSRD and OFDS VI can
ing in the neonatal period, and ocular motor apraxia4as well as
ical finding in OFDS VI but is only rarely observed in JSRD.3
Furthermore, tongue hamartoma, bucco-alveolar frenula, or
hallmarks of JSRD include cerebellar vermis hypoplasia in com-
bination with the “molar tooth sign” (MTS), a complex malfor-
superior cerebellar peduncles and an abnormally deep interpe-
duncular fossa.6These findings are also found in OFD VI.6Hy-
pothalamic hamartoma (HH) is a specific, but not consistently
be made prenatally before 24 weeks’ gestation.8In this report,
we describe prenatal and neonatal MR findings in OFDS VI.
ral-facial-digital syndrome type VI (OFDS VI) or Va ´radi-
Papp syndrome (OMIM 277170) is a rare autosomal reces-
A boy was born at 38 weeks’ gestation to a 34-year-old mother. He was
the second child of nonconsanguineous and healthy Swiss parents. A
sia of the cerebellar vermis. Therefore, a fetal MR imaging examination
ened and elongated superior cerebellar peduncles, corresponding to a
MTS (Fig 1A), and a hypothalamic mass representing HH (Fig 1A–C).
boy was born by cesarean delivery because of breech presentation and
macrocephaly. Apgar scores were 7, 8, and 9 at 1, 5, and 10 minutes,
respectively. Birth weight was 3850 g (90th–95th percentile), length 50
cm (25th–50th percentile), and head circumference 39.5 cm (3.8 cm
set ears, flat nasal bridge, multiple bucco-alveolar frenula, and postaxial
hexadactyly of both hands. Neurologic examination showed limb mus-
cular hypertonia. In the first hours, he developed recurrent respiratory
patterns of alternating tachypnea with respiratory rates up to 200 and
vermis agenesis, cerebellar hemispheric hypoplasia, an enlarged fourth
fossa abnormalities9and permits superior discrimination and
resolution of the different anatomic structures compared with
sonography. Doherty et al8reported prenatal MR findings of a
fetus with a risk for JSRD at 21 weeks’ gestation. MR imaging
connection between the fourth ventricle and fossa posterior.
However, a typical MTS was not seen. Fluss et al10reported a
of a typical MTS. In the case of our patient, the MTS was also
identifiable at 29 weeks’ gestation. Therefore, fetal MR imaging
Two articles reported prenatal sonography findings of OFDS
VI such as polydactyly and abnormalities in the posterior fossa,
but prenatal MR imaging was not performed.11,12Prenatal MR
findings of OFDS VI have not been reported previously. Neuro-
sia and the MTS, whereas HH is occasionally found. However,
HH is a finding of Pallister-Hall syndrome.13On MR imaging,
HH appears isointense compared with gray matter on T1-
weighted sequences and isointense to slightly hyperintense on
T2-weighted sequences.14Prenatal diagnosis of nonsyndromic
HH had been reported in 1 patient at 26 weeks’ gestation.15
In the case of our patient, HH was identifiable at 29 weeks’
In conclusion, a prenatal diagnosis of OFDS VI is possible
with fetal MR imaging from 29 weeks’ gestation. Therefore, if
prenatal MR imaging shows findings compatible with JSRD, an
HH should be sought. However, because of the rarity of the dis-
Received December 14, 2007; accepted after revision December 30.
From the Departments of Pediatric Neurology (A.P., E.B.), Diagnostic Imaging (U.B., I.S.),
and Neonatology and Intensive Care (V.B.), University Children’s Hospital of Zurich, Zurich,
Please address correspondence to Eugen Boltshauser, Department of Pediatric Neurology,
University Children’s Hospital, Steinwiesstr 75, 8032 Zurich, Switzerland; e-mail:
Poretti ? AJNR 29 ? Jun-Jul 2008 ? www.ajnr.org
We thank Beth Padden, MD, for help in editing the manu-
script. Dr. Poretti was financially supported by a donation
at the request of an anonymous client.
1. Va ´radiV,SzaboL,PappZ.Syndromeofpolydactyly,cleftlip/palateorlinguallump,
3. Parisi MA, Doherty D, Chance PF, et al. Joubert syndrome (and related disor-
ders) (OMIM 213300). Eur J Hum Genet 2007;15:511–21
4. Maria BL, Boltshauser E, Palmer SC, et al. Clinical features and revised diag-
nostic criteria in Joubert syndrome. J Child Neurol 1999;14:583–90
5. Braddock SR, Henley KM, Maria BL. The face of Joubert syndrome: a study of
dysmorphology and anthropometry. Am J Med Genet A 2007;143:3235–42
6. Gleeson JG, Keeler LC, Parisi MA, et al. Molar tooth sign of the midbrain-
hindbrain junction: occurrence in multiple distinct syndromes. Am J Med
Genet A 2004;125:125–34
for Joubert syndrome by ultrasound and MRI. Prenat Diagn 2005;25:442–47
9. Adamsbaum C, Moutard ML, Andre C, et al. MRI of the fetal posterior fossa.
Pediatr Radiol 2005;35:124–40
10. Fluss J, Blaser S, Chitayat D, et al. Molar tooth sign in fetal brain magnetic
related disorders. J Child Neurol 2006;21:320–24
11. Guven MA, Ceylaner S, Prefumo F, et al. Prenatal sonographic findings in a
case of Varadi-Papp syndrome. Prenat Diagn 2004;24:989–91
in an infant with OFD VI. Am J Med Genet A 2006;140:2146–49
14. Freeman JL, Coleman LT, Wellard RM, et al. MR imaging and spectroscopic
Am J Neuroradiol 2004;25:450–62
15. Booth TN, Timmons C, Shapiro K, et al. Pre- and postnatal MR imaging of
hypothalamic hamartomas associated with arachnoid cysts. AJNR Am J Neu-
Fig 1. Fetal T2-weighted MR imaging at 29 gestational weeks. A, Axial MR image showing hypoplasia of both cerebellar hemispheres, the characteristic MTS (thin arrow) with thickened
and elongated superior cerebellar peduncles and an abnormally deep interpeduncular fossa, and an HH (thick arrow). B, Sagittal MR image revealing significant hypoplasia of the cerebellar
vermis (arrow), an enlarged fourth ventricle and posterior fossa, an HH (white arrow), and a thin brain stem. C, Coronal MR image demonstrating an HH (white arrow).
Fig 2. T2-weighted MR imaging at 2 days of age. A, Axial MR image showing hypoplasia of the vermis and both cerebellar hemispheres, the characteristic MTS (thin arrow) with thickened
and elongated superior cerebellar peduncles, an abnormally deep interpeduncular fossa, and an HH (thick arrow). B, Sagittal MR image revealing significant hypoplasia of the cerebellar
vermis and dysplasia of the remnants of the cerebellar vermis (arrow), an enlarged fourth ventricle and posterior fossa, and an HH (white arrow). In addition, the corpus callosum and the
brain stem are hypoplastic, the pituitary stalk is thick, and the interthalamic adhesion is large. C, Coronal MR image demonstrating an HH (arrow), a missing left leaf of the septum
pellucidum, a bulky left fornix, and a probably dysplastic cerebral cortex in the left Sylvian fissure.
AJNR Am J Neuroradiol 29:1090–91 ? Jun-Jul 2008 ? www.ajnr.org