Null variants and deletions in BRWD3 cause an X-linked syndrome of mild-moderate intellectual disability, macrocephaly, and obesity: A series of 17 patients

Type Article

Journal Article


P. J. Ostrowski; A. Zachariou; C. Loveday; D. Baralle; E. Blair; S. Douzgou; M. Field; A. Foster; C. Kyle; K. Lachlan; S. Mansour; S. Naik; G. Rea; S. Smithson; Y. Sznajer; E. Thompson; T. Cole; K. Tatton-Brown

Year of publication



Am J Med Genet C Semin Med Genet








BRWD3 has been described as a cause of X-linked intellectual disability, but relatively little is known about the specific phenotype. We report the largest BRWD3 patient series to date, comprising 17 males with 12 distinct null variants and 2 partial gene deletions. All patients presented with intellectual disability, which was classified as moderate (65%) or mild (35%). Behavioral issues were present in 75% of patients, including aggressive behavior, attention deficit/hyperactivity and/or autistic spectrum disorders. Mean head circumference was +2.8 SD (2.8 standard deviations above the mean), and mean BMI was +2.0 SD (in the context of a mean height of +1.3 SD), indicating a predominant macrocephaly/obesity phenotype. Shared facial features included a tall chin, prognathism, broad forehead, and prominent supraorbital ridge. Additional features, reported in a minority (