Xia-Gibbs Syndrome

A number sign (#) is used with this entry because of evidence that Xia-Gibbs syndrome is caused by heterozygous mutation in the AHDC1 gene (615790) on chromosome 1p36.

Clinical Features

Xia et al. (2014) reported 4 unrelated children with mental retardation. All had failure to thrive, hypotonia, and delayed psychomotor development with absent or poor expressive language. Mild dysmorphic features were present, including low-set or protuberant ears, flat nasal bridge, esotropia, hypertelorism, up- or downslanting palpebral fissures, and micrognathia. All also had obstructive sleep apnea, and 3 had laryngomalacia or tracheomalacia. Brain MRI showed hypoplasia of the corpus callosum, simplified gyral pattern, and delayed myelination; 2 patients had a retrocerebellar cyst.

Molecular Genetics

In a girl with mental retardation, Xia et al. (2014) identified a de novo heterozygous truncating mutation in the AHDC1 gene (615790.0001). The mutation was found by whole-exome sequencing. Targeted sequencing of the AHDC1 gene in 2,000 additional patients identified 3 patients with a similar disorder who had de novo heterozygous truncating mutations (615790.0002-615790.0003). Functional studies of the variants were not performed.