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Letters to the Editor

Indian Pediatrics 2005; 42:494-495

Joubert Syndrome Associated with Lissencephaly


Joubert syndrome (JS) is a rare autosomal recessive disorder characterized by clinical (hypotonia, ataxia and general develop-mental delay) and neuroradiological findings. Neuroimaging of JS reveals deeper than normal posterior interpeduncular fossa, prominent or thickened superior cerebellar peduncles, and vermian hypoplasia or dysplasia leading to the so called molar tooth sign(1).

Lissencephaly is a rare and severe cortical malformation that shows evidence of wide-spread incomplete neuronal migration. The spectrum ranges from complete absence of gyri (agyria) to broad gyri with reduced sulci (pachygyria), with an abnormally thick cortex(2).

The majority of JS cases have morpho-logically normal cerebrums and cerebellar hemispheres, but lateral ventricular enlargement due to atrophy, and corpus callosum dysgenesis were described. To our know-ledge, JS associated with lissencephaly was very rarely reported(3,4).

A 3-year-old infant was admitted to our clinic because of seizures and marked psycho-motor developmental delay. The patient was capable of head controlling, smiling to mother, and supportive sitting at 7, 8 and 10 months, respectively. He had also abnormal breathing pattern as alternating periods of predominantly hyperpnea and apnea within first month. His parents were first-degree cousins. His head circumference was normal. He was poorly contacting with surroundings. He could not sit without support. Axial hypotonia and spastic left hemiparesis were detected. Neuro-ophthalmological examination was within normal limits. Electro-encephalogram and metabolic screening revealed no abnormalities. Abdominal ultra-sound examination was normal. Cranial MRI showed characteristic imaging of JS including bat-wing shaped fourth ventricle, elongated and stretched superior cerebellar peduncles, hypoplasia of the cerebellar vermis (Fig. 1). Cerebellar hemispheres were normal. In addition, a flattened and thickened cerebral cortex with gyration anomalies predominantly in the frontotemporal areas with opercular hypoplasia and lissencephaly were noted. The patient was diagnosed as JS asssociated with lissencephaly. The patient was put on phenobarbital and physical therapy. At two years of age, he was hypotonic, and still could not sit without support, but his spastic left hemiparesis markedly improved. His head circumference did not reach to age- normal levels (46.5 cm, <5 p). Although the patient learned to sit without support approximately at three years of age, he did not talk and walk.

Fig. 1. Axial T1 weighted image demonstrates characteristic bat wing dilatation of fourth ventricle and elongated superior cerebellar peduncles.

In a study of 21 unrelated and 6 related JS families, both chromosome 9q34 and 17p11.2 JS loci were excluded in 26 JS families. They have also searched and excluded the candidate genes EN1, EN2, FGF8, and BARHL1 from a direct pathogenetic role in JS(5). Genetic studies and many variable phenotypes of JS suggest that there is heterogeneity in genetic basis of JS.

Hamit Ozyurek,
Gulsen Kose,

Hacettepe University Faculty of Medicine,
Pediatric Neurology Unit, Ankara, Turkey and
Ankara Social Security Children’s Hospital,
Pediatric Neurology Unit, Ankara, Turkey.
Correspondence to:

Dr. Hamit Ozyurek,

Guzelyali Mah. 129 Sokak
Palmiye Sitesi A Block, Kat:8 Daire:15
Seyhan/Adana, Turkey.
E-mail: [email protected]

References

1. Maria BL, Boltshauser E, Palmer SC, Tran TX. Clinical features and revised diagnostic criteria in Joubert syndrome. J Child Neurol 1999; 14: 583-591.

2. Leventer RJ, Pilz DT, Matsumoto N, Ledbetter DH, Dobyns WB. Lissencephaly and sub-cortical band heterotopia: molecular basis and diagnosis. Mol Med Today 2000; 6: 277-284.

3. Maria BL, Quisling RG, Rosainz LC, et al. Molar tooth sign in Joubert syndrome: Clinical, radiologic, and pathologic significance. J Child Neurol 1999;14: 368-376.

4. Patel S, Barkovich AJ. Analysis and classification of cerebellar malformations. AJNR Am J Neuroradiol 2002; 23: 1074-1087.

5. Blair IP, Gibson RR, Bennett CL, Chance PF. Search for genes involved in Joubert syndrome. Evidence that one or more major loci are yet to be identified and exclusion of candidate genes EN1, EN2, FGF8, and BARHL 1. Am J Med Genet 2002; 107: 190-196.

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