Joubert syndrome is an autosomal – recessive developmental disorder with an incidence of approximately 1:100 000. It is characterized by cerebellar vermis hypoplasia, cerebellar ataxia, muscular hypotension, oculomotor apraxia, neonatal respiratory distress, mental retardation as well as retinal degeneration. It is therefore also described as cerebello-oculo-renal syndrome. Additionally Joubert syndrome can be associated with hepatic fibrosis, ocular coloboma and polydactyly. There is a high phenotypic variability even within families. The unifying pathognomonic sign is a cerebellar vermis hypoplasia presenting in MRI as the so called “molar tooth sign”.

Approximately 25% of patients with JS present with NPH depending on the underlying genetic defect. At the moment mutations in 22 genes are known to cause JS of witch AHI1, RPGRIP1L and CC2DA2 are the most frequently affected accounting for 10% of JS cases each.

Due to clinical and genetic overlap JS is hard to differentiate from other ciliopathies. For certain genes a correlation between the type of genetic change and the clinical presentation could be made: while two heterozygous truncating mutation in NPHP6/CEP290 lead to a severe phenotype of Meckel – Gruber syndrome, the presence of at least one missense mutation leads to a milder, late onset phenotype with involvement of isolated organs. Mutations in NPHP1 have also been described as a cause of JS but account only for less than two percent of cases.

molar tooth sign in MRI

molar tooth sign in MRI

dysplastic kidney in JS