Letters to the Editor Indian Pediatrics 2005; 42:494-495 |
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Joubert Syndrome Associated with Lissencephaly |
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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.
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,
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