Smith-Magenis syndrome (SMS), a probable contiguous gene syndrome due to del 17p11.2, is associated with a distinct phenotype of characteristic physical features, developmental delay, speech delay with or without associated hearing loss, clinical signs of peripheral neuropathy, and neurobehavioral problems including sleep disturbance, outbursts and self- injurious behaviors. First reported by Smith et al. in 1982, over 200 individuals representing a diversity of ethnic backgrounds have been identified with the syndrome worldwide. Despite improved cytogenetic techniques, the diagnosis of SMS is often delayed until early school age. Defining the infant phenotype to promote early diagnosis is a priority. Research on the specific oral-motor, voice and otolaryngologic findings related to speech dysfunction in SMS continues. Baseline studies show major lingual findings and one or more laryngeal findings in virtually all patients. Speech delay was exhibited in 80% of verbal children; hearing loss in 60%. These findings provide a physiologic explanation for the functional impairment in voice and speech previously reported in SMS and suggest a possible gene in the SMS critical region involved in development of laryngeal and pharyngeal structures. Elevated total and LDL cholesterol observed in over two thirds of subjects is intriguing given that the gene for sterol regulatory element binding protein (SREBF1) maps to 17p11.2. Patients are seen under Protocol 95HG0010 by an interdisciplinary team of researchers with research focused on delineating the natural history and pathophysiology of SMS across the lifespan.
