Smith-Magenis Syndrome: Genetic Basis and Clinical Implications

Smith-Magenis syndrome (SMS) is a neurobehavioral disorder associated with deletions and mutations of the RAI1 gene on chromosome 17p11.2. Clinical features of the syndrome include intellectual disability, sleep disturbance, craniofacial differences, and a distinctive profile of stereotypic and self-injurious behaviors. Although the functional role of RAI1 and neighboring genes is not completely understood, disruption of these genes is thought to contribute to specific clinical features of the disorder. Maladaptive behaviors in people with SMS appear to reflect a complex interplay between physiology and environment that may be further compounded by an underlying developmental asynchrony. Management requires a multidisciplinary approach and involves treatment for sleep disturbance, speech and occupational therapies, medical monitoring, educational and behavioral interventions, and family support.