Stocco Dos Santos X-Linked Mental Retardation Syndrome

A number sign (#) is used with this entry because of evidence that Stocco dos Santos X-linked mental retardation syndrome (SDSX) is caused by mutation in the SHROOM4 gene (300579) on chromosome Xp11.

Clinical Features

Stocco dos Santos et al. (1991) described a Brazilian family in which 4 males had severe mental retardation, bilateral congenital hip luxation, and short stature. Five uncles of these males may have been affected. Three of the affected males had a G6PD variant, G6PD Butantan (see 305900), which apparently did not segregate completely with mental retardation. Stocco dos Santos et al. (2003) further delineated the X-linked mental retardation syndrome in this family.

Lopes et al. (2016) reported a 14-year-old boy (patient 19) with delayed psychomotor development, severe intellectual disability, absent speech, dyspraxic gait, microcephaly, bruxism, and kyphosis/scoliosis. Additional features included gastroesophageal reflux, peripheral vasomotor disturbances, diminished response to pain, and autistic traits. Brain imaging was normal and he did not have seizures. The patient had some features reminiscent of Rett syndrome (RTT; 312750), including small cold hands and feet and intense eye communication, but sequence analysis of the MECP2 gene (300005) revealed no mutations.

Inheritance

The transmission pattern of SDSX in the family reported by Lopes et al. (2016) was consistent with X-linked recessive inheritance.

Mapping

By linkage analysis in a Brazilian family with a mental retardation syndrome, Hagens et al. (2006) identified a locus for the disorder on Xp11.3-q21.1, with a maximum lod score of 3.14 at the androgen receptor (AR; 313700) and DXS983 loci.

Molecular Genetics

Hagens et al. (2006) identified a missense mutation in the SHROOM4 gene (300579.0001) that segregated with the X-linked mental retardation syndrome in the family described by Stocco dos Santos et al. (1991, 2003).

In a 14-year-old boy with SDSX, Lopes et al. (2016) identified a hemizygous missense mutation in the SHROOM4 gene (R146W; 300579.0002). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was inherited from the patient's unaffected mother. Functional studies of the variant and studies of patient cells were not performed.