Ocular and renal features often seen in conjunction with Joubert syndrome together constitute the cerebellooculorenal syndromes (CORSs). Cerebellooculorenal syndromes are a group of autosomal recessive syndromes characterized by the variable association of brain, eye, and kidney abnormalities, plus occasional malformations in other organs such as the liver.
Keeler et al. (2003) performed a genome scan in a consanguineous (first cousins) family from the United Arab Emirates with cerebellooculorenal syndrome 2. The mother had six pregnancies with two affected female children. The 15-year-old affected child had hydrocephalus at birth, requiring a ventriculoperitoneal shunt. Facial dysmorphic features included a depressed nasal bridge with hypertelorism, high-arched palate, and low-set ears. There were no abnormal eye movements or panting respirations in the neonatal period, although she displayed severe hypotonia and developmental delay. Brain MRI showed the MTI, absence of the cerebellar vermis, and abnormal kinked corpus callosum. The occipital cortex appeared malformed, with possible polymicrogyria. Ophthalmological examination showed double contoured coloboma of the retina and choroid below the optic disk, as well as optic atrophy and impaired vision. The 5-year-old affected child had an enlarged head circumference at birth and required a ventriculoperitoneal shunt for hydrocephalus at age 14 months. She had similar facial dysmorphisms, as well as panting respirations, jerky eye movements, hypotonia, and mental retardation. Brain MRI showed the MTI, thin corpus callosum, and possibly malformed occipital cortex. Ophthalmological examination showed bilateral coloboma of the optic-nerve head. Abdominal ultrasound in both affected children showed normal-sized liver and kidneys. Karyotype in both children was normal. However, linkage analysis defined a novel locus on chromosome 11p12-q13.3, with a maximum two-point LOD score of Z=5.2 at the marker D11S1915. This finding, lead Keeler et al. (2003) to propose that the cerebellooculorenal form of Joubert syndrome is a distinct genetic entity from the Joubert syndrome 1 locus at chromosome 9, in which there is minimal involvement of retina or kidney.