Smith–Magenis Syndrome

Smith–Magenis syndrome (SMS) is a multiple congenital anomalies condition associated with a complex neurobehavioral phenotype, intellectual disability, significant sleep disorder, and childhood-onset obesity. The majority of persons with SMS harbor a heterozygous deletion within chromosome 17p11.2, while a smaller percentage (~5%) have a nucleotide variant in the dosage-sensitive RAI1 gene within that region. The age at diagnosis of SMS spans from prenatal to adulthood, owing to both the variability of clinical features and the availability of robust laboratory analyses including chromosome microarray analysis, gene panel testing, and exome sequencing. Smith–Magenis syndrome was first described in 1982 and while the clinical features are now well delineated, the management of the challenging behaviors, disrupted sleep, and obesity remains a challenge.