Seizures, Cortical Blindness, And Microcephaly Syndrome

A number sign (#) is used with this entry because of evidence that seizures, cortical blindness, and microcephaly syndrome (SCBMS) is caused by homozygous mutation in the DIAPH1 gene (602121) on chromosome 5q31.

Description

Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (summary by Ercan-Sencicek et al., 2015).

Clinical Features

Ercan-Sencicek et al. (2015) reported a consanguineous Saudi Arabian family in which 5 sibs had microcephaly, cortical visual impairment, and early-onset seizures. All had significantly delayed psychomotor development with severe intellectual disability and very poor speech, necessitating full-time care. Other features included short stature and hypoplasia of the corpus callosum.

Al-Maawali et al. (2016) reported 4 patients from 2 unrelated consanguineous Arab families with early-onset seizures, microcephaly, severely delayed psychomotor development, and cortical blindness with optic atrophy. The patients showed poor overall growth with short stature; some had hypotonia.

Inheritance

The transmission pattern of SCBMS in the family reported by Ercan-Sencicek et al. (2015) was consistent with autosomal recessive inheritance.

Mapping

By genomewide linkage analysis of a consanguineous Saudi Arabian family with SCBMS, Ercan-Sencicek et al. (2015) found linkage to a region on chromosome 5q31.3 (maximum lod score of 3.7).

Molecular Genetics

In 5 sibs, born of consanguineous Saudi Arabian parents, with SCBMS, Ercan-Sencicek et al. (2015) identified a homozygous truncating mutation in the DIAPH1 gene (Q778X; 602121.0002). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family.

Al-Maawali et al. (2016) identified 2 different homozygous truncating mutations in the DIAPH1 gene (602121.0003 and 602121.0004) in 4 patients from 2 unrelated consanguineous Arab families with SCBMS.