The chromosome 9q subtelomere deletion syndrome

AbstractThe chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative micro‐ or brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid‐face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down‐turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub‐microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haplo‐insufficiency of EHMT1, a gene whose protein product (Eu‐HMTase1) is a histone H3 Lys 9 (H3‐K9) methyltransferase. This wa