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.
Joubert syndrome does not appear to have a gender or racial bias and prevalence varies between 1/80,000 to 1/100,000 live births. The syndrome has an onset in infancy and prognosis depends on the severity of symptoms and the extent of cerebellar vermian hypoplasia. Patients may require kidney transplants, mobility aids as well as physical, occupational and speech therapy.
Al-Hamed et al. (2016) studied a cohort of 44 Saudi families affected by antenatal cystic kidney disease. In one consanguineous family, the antenatal ultrasound examination found cystic kidneys along with oligohydramnios/anhydramnios. The proband had three other affected siblings and the case resulted in fetal death. Genetic screening of 90 renal genes found the fetus to be compound heterozygous for known mutations in the RPGRIP1L gene (c.640G>A p.V214I; C.685G>A, p.A229T). The first mutation was predicted to be pathogenic while the second had been shown to compromise the interaction of RPGRIP1L with RPGR.