Joubert Syndrome 23

A number sign (#) is used with this entry because of evidence that Joubert syndrome-23 (JBTS23) is caused by homozygous or compound heterozygous mutation in the KIAA0586 gene (610178) on chromosome 14q23.

Description

Joubert syndrome-23 is an autosomal recessive neurodevelopmental disorder characterized by delayed development, abnormal eye movements, and abnormal breathing pattern associated with a characteristic hindbrain malformation apparent on brain imaging and known as the 'molar tooth sign.' Compared to other forms of Joubert syndrome, the phenotype is relatively mild, and other organ systems are generally not affected (summary by Bachmann-Gagescu et al., 2015).

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

Clinical Features

Bachmann-Gagescu et al. (2015) reported 9 patients with Joubert syndrome-23. The phenotype was relatively homogeneous, consisting mainly of neurologic features, such as delayed development, abnormal eye movements, and the molar tooth sign on brain imaging. Two individuals had brainstem heterotopia, 1 had dysplasia of the cerebellar hemispheres, and 1 had a thick and dysplastic corpus callosum. Many patients had abnormal breathing patterns. Only 1 patient had polydactyly, and another had coloboma; none had retinal, renal, or liver involvement. Bachmann-Gagescu et al. (2015) concluded that the phenotype was at the mild end of the disease spectrum observed in Joubert syndrome.

Inheritance

The transmission pattern of JBTS23 in the families reported by Bachmann-Gagescu et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In affected individuals from 9 unrelated families with JBTS23, Bachmann-Gagescu et al. (2015) identified homozygous or compound heterozygous mutations in the KIAA0586 gene (see, e.g., 610178.0001-610178.0005). Mutations in the first patient were found by whole-exome sequencing; biallelic mutations in 8 additional families were found by sequencing the exons of the KIAA0586 gene in a cohort of 366 additional families with the disorder. Overall, biallelic mutations were found in 9 (2.5%) of 366 families. Seven additional patients had heterozygous mutations in the KIAA0586 gene. One recurrent truncating mutation (610178.0001) was found in 7 of the 9 families. Functional studies of the variants were not performed.