Mental Retardation, Anterior Maxillary Protrusion, And Strabismus

A number sign (#) is used with this entry because this phenotype, characterized by mental retardation, anterior maxillary protrusion, and strabismus (MRAMS), is caused by homozygous mutation in the SOBP gene (613667).

Clinical Features

Basel-Vanagaite et al. (2007) reported 7 sibs, born of consanguineous parents of Israeli Arab descent, with a syndrome characterized by severe mental retardation, anterior maxillary protrusion, and strabismus. Six of 7 sibs had anterior maxillary protrusion with vertical maxillary excess, open bite, and prominent crowded teeth. The patient with mental retardation but without a jaw anomaly was somewhat less severely retarded and developed seizures and severe psychosis in adolescence. None of the unaffected sibs with normal intelligence had jaw or dental anomalies. Routine laboratory studies, brain MRI, and cytogenetic studies were all normal. Birk et al. (2010) reported follow-up of the family reported by Basel-Vanagaite et al. (2007). One patient had esotropia and amblyopia with reduced vision and hypermetropia. Another showed mild cochlear hearing loss. The 1 patient without maxillary features and strabismus had temporal lobe epilepsy beginning at age 11 years and developed psychotic symptoms at age 13.

Mapping

By genomewide linkage and haplotype analysis of the family with MRAMS reported by Basel-Vanagaite et al. (2007), Birk et al. (2010) identified a common 9.8-Mb region on chromosome 6q21 between D6S449 and rs2235989 (2-point lod score of 4.45), containing 36 known or predicted genes.

Molecular Genetics

By candidate gene sequencing of the 6q21 locus, Birk et al. (2010) identified a homozygous mutation in the SOBP gene (R661X; 613667.0001) in affected members of the family with MRAMS reported by Basel-Vanagaite et al. (2007). Linkage analysis excluded the SOBP locus in 22 additional families with syndromic intellectual disability.