Joubert syndrome 9 is a multisystem disorder characterized by brain anomalies such as cerebellar vermis 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. Symptoms of JBTS9 may include neurological problems such as intellectual disability, seizures and ventriculomegaly, ophthalmological anomalies such as retinitis pigmentosa, astigmatism, nystagmus and cataract as well as renal and hepatic abnormalities such as nephronophthisis and hepatosplenomegaly.
JBTS9 follows an autosomal recessive pattern of inheritance. It is caused by mutations in the CC2D2A gene, which encodes a ciliary protein that helps prevent the diffusion of transmembrane proteins between the cilia and plasma membranes. The CC2D2A protein is also predicted to be involved in primary cilium assembly, determination of left/right symmetry and embryonic brain development. Mutations in this gene associated with JBTS9 usually include homozygous and compound heterozygous transitions and indels. Interestingly, digenic inheritance has also been seen in this disorder; some Joubert syndrome patients have been reported to carry a heterozygous mutation in the CC2D2A gene along with a heterozygous mutation in the CEP41 gene.