There is substantial overlap in the phenotype of individuals with SMS resulting from specific RAI1 point mutations and those with SMS caused by 17p11.2 deletions [17, 18], suggesting that the core features of SMS, including most aspects of the neurobehavioural phenotype, are caused by haploinsufficiency of RAI1. The common clinical phenotype associated with SMS is mild to moderate ID, hearing impairments, delayed speech, dysmorphic facial features and cardiovascular and renal abnormalities, amongst many others [17, 19–21]. Here, RAI1 is linked to Smith-Magenis syndrome.