Wilson-Turner X-Linked Mental Retardation Syndrome

A number sign (#) is used with this entry because of evidence that Wilson-turner X-linked mental retardation syndrome (WTS) is caused by hemizygous mutation in the LAS1L gene (300964) on chromosome Xq12.

Description

Wilson-Turner syndrome is an X-linked recessive neurologic disorder characterized by intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Females are unaffected (Wilson et al., 1991).

Clinical Features

Wilson et al. (1991) described a kindred in which males in 5 successive generations in an X-linked recessive pedigree pattern had a mental retardation syndrome. The 14 living males in the 3 most recent generations permitted definition of other features: obesity, gynecomastia, speech difficulties, emotional lability, tapering fingers, and small feet. Some of the features resembled those of Borjeson-Forssman-Lehmann syndrome (BFLS; 301900), but the patients of Wilson et al. (1991) did not have hypermetropia or cataracts in later life and did not have elongated earlobes. As pointed out by Frezal (1992), the same condition was reported by Vasquez et al. (1979). Turner (1992) had suggested that the patients of Vasquez et al. (1979) might have had BFLS.

Hu et al. (2016) reported a French family in which 5 males spanning 3 generations had MRXS6. They had intellectual disability with speech impairment, obesity, and hypogonadism.

Inheritance

The transmission pattern of WTS in the family reported by Wilson et al. (1991) was consistent with X-linked recessive inheritance.

Mapping

By linkage analysis of a family with syndromic X-linked mental retardation, Wilson et al. (1991) found linkage to chromosome Xp21.1-q22 between DXS84 and DXS94. No recombination was found with DXS255; maximum lod = 4.82 at theta = 0.0. The mapping information made the distinction from Borjeson-Forssman-Lehmann syndrome quite definite, inasmuch as the gene for BFLS had been provisionally localized to Xq26-q27.

Molecular Genetics

In affected members of the family with WTS reported by Wilson et al. (1991), Hu et al. (2016) identified a hemizygous missense mutation in the LAS1L gene (A269G; 300964.0001). Affected members of a French family with MRXS6 were found to carry a different heterozygous LAS1L mutation (R415W; 300964.0002). The mutations, which were found by X-chromosome exome sequencing, segregated with the disorder in the families. Functional studies of the variants were not performed.