Field et al. (2007) identified 3 families with X-linked mental retardation (XLMR) associated with macrocephaly. The first family included a nephew and an uncle with mild to moderate metal retardation and an aunt with mild cognitive difficulties during ... Field et al. (2007) identified 3 families with X-linked mental retardation (XLMR) associated with macrocephaly. The first family included a nephew and an uncle with mild to moderate metal retardation and an aunt with mild cognitive difficulties during early childhood. The height, weight, and head circumference of the nephew were consistently greater than the 97th percentile. His height at age 17 years was 190 cm and head circumference was 62 cm. The right testis was undescended and was brought down by orchiopexy at age 13 months. Muscular hypotonia was noted in early life. Facial features included a long face, pointed chin, and large, prominent ears. The uncle's height was 187 cm and head circumference was 59 cm, with frontal bossing, large and prominent ears, and a pointed chin. His build was thin, with midthoracic kyphosis and minimal pectus excavatum. The second family included 2 half-brothers who shared the same mother, who was reported to have an intellectual disability and head circumference at the 97th percentile. The elder had an undescended testis; the younger had mild muscular hypotonia. Evaluated at ages 13 and 9 years, both had head circumference at greater than the 97th percentile, frontal bossing, pointed chin, and prominent ears with cupped helices. The third family was originally reported by Gedeon et al. (1994) (as family 'E') and included 3 brothers, a cousin, and an uncle, all with borderline to mild mental retardation. None of the affected males had macrocephaly or tall stature in childhood. They had large, prominent ears, triangular face, and pointed chin.
In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic XLMR, Field et al. (2007) identified 2 families with truncating mutations in BRWD3. In both families, the mutation segregated with the phenotype ... In the course of systematic screening of the X-chromosome coding sequences in 250 families with nonsyndromic XLMR, Field et al. (2007) identified 2 families with truncating mutations in BRWD3. In both families, the mutation segregated with the phenotype in affected males. In a family in which an uncle and nephew had XLMR with macrocephaly, Field et al. (2007) described a splice site mutation in the BRWD3 gene (300553.0001). Three carrier females were identified and all 3 of the chromosomes carrying the mutation were preferentially inactivated. In a family in which 2 half-brothers had LXMR with macrocephaly, Field et al. (2007) identified a 1-bp insertion in the BRWD3 gene (300553.0002). In the family described by Gedeon et al. (1994), Field et al. (2007) identified a missense mutation in BRWD3 (K1596E; 300553.0003). Tarpey et al. (2009) sequenced the coding exons of the X chromosome in 208 families with X-linked mental retardation. In 2 individuals they identified nonrecurrent truncating mutations in the BRWD3 gene that segregated with mental retardation in their families. In addition to X-linked mental retardation, affected individuals had macrocephaly.