Joubert Syndrome 2

Alternative Names

  • JBTS2
  • Cerebellooculorenal Syndrome 2
  • CORS2
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

608091

Mode of Inheritance

Autosomal recessive

Gene Map Locus

11p12-q13.3

Description

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.

Molecular Genetics

The molecular basis for the cerebellar anomalies seen in Joubert syndrome patients is unknown and is likely genetically distinct from classical Joubert syndrome. Mutations in genes that regulate early specification and development of domains of the cerebellum may be responsible for the brain abnormalities observed in Joubert syndrome. The early specification of cerebellar territory in vertebrates is regulated via the expression of homeotic genes. These homeotic genes are homologous to the segment-polarity genes in Drosophila, which encode transcription factors known as "paired-box," or Pax genes. Their transcripts influence the expression of vertebrate homologues of engrailed (en), a Drosophila gene encoding a transcription factor containing a homeobox domain. The expression of en genes is further regulated by wnt1, a homologue of the Drosophila wingless gene. The wnt1 gene is primarily expressed during early neuronal development. Disruption of wnt1 results in agenesis of cerebellar structures. Recently, the wnt1 gene has been excluded as being causative for Joubert syndrome.

Epidemiology in the Arab World

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Other Reports

United Arab Emirates

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.  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. Sibling was similarly affacted. 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 led 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.

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