Cases suspected to have SMS, but without a 17p11.2 deletion, should prompt consideration of RAI1 mutation analysis, if their features include AGA term birth, childhood onset obesity (increased BMI for age), ocular abnormalities, hoarse voice, middle ear dysfunction and hearing loss, and behavioral aspects, especially self-injurious behavior, nail damage, and problems regulating food intake (i.e., insatiable appetite), in the absence of immunological abnormalities and cardiovascular or renal structural anomalies. Here, RAI1 is linked to Smith-Magenis syndrome.