Molar tooth sign in Joubert syndrome: Clinical, radiologic, and pathologicsignificance

Joubert syndrome is a rare autosomal-recessive condition characterized by e arly hyperpnea and apnea, developmental delay, and truncal ataxia. We previ ously described key ocular motor signs in Joubert syndrome and the molar to oth sign resulting from dysplasia of the isthmic segment of the brain stem, superior cerebellar peduncles, and vermis. In this study, we obtained clin ical and developmental data in 61 cases, and radiologic data in 46 of these , to determine the prevalence of the molar tooth sign in a large sample, an d to ensure that magnetic resonance images obtained for study were represen tative of the Joubert syndrome population at large. We studied the morpholo gy of the isthmic segment of the pontomesencephalic junction, the segment o f the brain stem derived from the primitive isthmus. Portions of the cerebe llum analyzed included the superior cerebellar peduncles, the anterior and posterior lobes of the vermis, and the flocculonodular lobe. Ln one case, a utopsy of the brain was performed. The average age at diagnosis was 33 mont hs. Ail patients were hypo tonic and developmentally delayed. The molar too th sign was present in 85% of cases with 13% of these showing additional ma lformations. All patients without the molar tooth sign had other mimicking conditions such as neocerebellar dysgenesis, isolated vermian atrophy, cere bellar aplasia, and cystic dilation of the cisterna magna. Autopsy showed a plasia of the cerebellar vermis with dysplasia of the dentate nucleus, elon gated locus coeruleus, and marked dysplasia of the caudal medulla. A better understanding of the clinical, radiologic, and pathologic features of Joub ert syndrome should help uncover the genetic basis for the syndrome.