Joubert syndrome is a phenotypically heterogeneous ciliopathy classically defined by brain anomalies such as cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa. These findings give the appearance of a molar tooth sign on a brain MRI. JBTS6 also results in neurological problems such as delayed psychomotor development, intellectual disability, ataxia and hypotonia. Other symptoms include breathing dysregulation, renal defects such as nephronophthisis, microcysts and renal failure, liver abnormalities such as hepatic fibrosis and bile duct proliferation, and ophthalmological impairments such as oculomotor apraxia, chorioretinal coloboma and blindness.
The disorder follows an autosomal recessive pattern of inheritance and is caused by mutations in the TMEM67 gene. This gene encodes a ciliary transmembrane protein believed to be involved in ciliogenesis and signaling. Both homozygous and compound heterozygous mutations in the TMEM67 gene are associated with JBTS6.