From Behavioral and Sleep Disturbances to Genetic Diagnosis: Smith-Magenis Syndrome and the Importance of the Diagnostic Pathway
Abstract
Smith-Magenis syndrome (SMS) is a rare multisystem genetic disorder caused by a 17p11.2 microdeletion or pathogenic variants in the retinoic acid-induced 1 (RAI1) gene. It is characterized by developmental delay, distinctive craniofacial features, behavioral dysregulation, and inverted sleep-wake rhythm. Because early clinical findings are often nonspecific, diagnosis is frequently delayed, and patients may initially present to child psychiatry services with behavioral complaints. We report a 5-year-old girl referred for hyperactivity, severe circadian sleep disturbance with recurrent nocturnal awakenings, self-injurious behaviors, sensory-seeking behaviors, and developmental delay. Comprehensive psychiatric, developmental, neurological, physical, and genetic evaluations revealed a 17p11.2 microdeletion involving both RAI1 and folliculin (FLCN). The diagnosis of SMS was confirmed, and the involvement of FLCN indicated additional potential long-term medical risks. This case underscores the importance of considering genetic etiologies in children presenting with severe behavioral dysregulation and sleep problems and highlights the critical role of comprehensive genetic assessment in guiding diagnosis, management, and long-term follow-up.
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