Joubert Syndrome 25

A number sign (#) is used with this entry because of evidence that Joubert syndrome-25 (JBTS25) is caused by homozygous or compound heterozygous mutation in the CEP104 gene (616690) on chromosome 1p36.

Description

Joubert syndrome-25 is an autosomal recessive ciliopathy characterized by delayed psychomotor development and oculomotor apraxia associated with cerebellar hypoplasia manifest as the molar tooth sign on brain imaging. The clinical manifestations appear to be confined to the neurologic system, as patients tend not to have additional renal, liver, or limb involvement (summary by Srour et al., 2015)

For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.

Clinical Features

Srour et al. (2015) reported 3 unrelated children with Joubert syndrome. All had a neurologic form of the disorder characterized by significantly delayed psychomotor development, oculomotor apraxia, and the molar tooth sign on brain imaging. Two patients had hypotonia and ataxia, 1 had breathing abnormalities, and 1 had an abnormal electroretinogram. None had renal, liver, or limb abnormalities.

Inheritance

The transmission pattern of JBTS25 in the families reported by Srour et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 3 unrelated children with Joubert syndrome-25, Srour et al. (2015) identified homozygous or compound heterozygous mutations in the CEP104 gene (616690.0001-616690.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Functional studies and studies on patient cells were not performed.