Mental Retardation, X-Linked, Syndromic 17

Clinical Features

Marom et al. (2011) reported a consanguineous Arab Muslim kindred in which 5 boys ranging in age from 8 months to 7.5 years had global developmental delay, delayed motor development, lack of speech development, and mental retardation. All patients also had alacrima, and 3 had achalasia or swallowing difficulties. Two patients had anisocoria. None had evidence of adrenal dysfunction or a neuropathy, and no dysmorphic features were mentioned. Marom et al. (2011) noted the phenotypic overlap with triple-A syndrome (231550), which can have variable features.

See also AAMR (615510), which is caused by mutation in the GMPPA gene (615495) on chromosome 2q35.

Mapping

By linkage analysis of a consanguineous Arab family with X-linked mental retardation associated with alacrima and achalasia, Marom et al. (2011) identified a shared 16.4-Mb continuous segment of identical alleles between markers rs2748314 and rs5906782 on chromosome Xp21.1-p11.23 (lod score of 1.8). Their findings suggested X-linked recessive inheritance, rather than autosomal recessive inheritance. The mother in 1 branch of the family had a fragile X premutation allele (55 repeats) in the FMR1 gene (309550), and her 3 sons with mental retardation had 66, 19, and 100 repeats, respectively. In addition, an affected boy in another branch of the family had normal fragile X results, suggesting that another genetic mechanism is responsible for the disorder. Genetic analysis excluded mutation in the aladin gene (AAAS; 605378), which is mutant in triple-A syndrome.