Joubert syndrome is a phenotypically heterogeneous ciliopathy classically defined by the presence of a molar tooth sign on brain imaging studies caused by cerebellar vermian hypoplasia and brainstem abnormalities. Symptoms of the subtype JBTS7 include developmental delay, intellectual disability, ataxia, hypotonia and breathing dysregulation. Ocular anomalies may include oculomotor apraxia, nystagmus, ptosis and strabismus. Skeletal defects may include postaxial polydactyly of both hands and feet as well as scoliosis. Renal defects include nephronophthisis, increased echogenicity and renal cysts, with most patients suffering from end stage renal disease by the first or second decade of life.
JBTS7 follows an autosomal recessive pattern of inheritance and is caused by mutations in the RPGRIP1L gene. The gene encodes a ciliary protein responsible for negatively regulating signaling through the G-protein coupled thromboxane A2 receptor. Both homozygous and compound heterozygous mutations in RPGRIP1L are associated with JBTS7.