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Incidence

Although the exact incidence is not known, it is estimated that SMS occurs in 1 out of 25,000 births. The condition is sporadic. Neither recurrence in families, nor germinal mosaicism have been hitherto reported. The microdeletion causing Smith-Magenis syndrome involves only one chromosome; therefore, the microdeletion acts in an autosomal dominant manner. Virtually all cases of SMS occur de novo.

Clinical Characteristics

Smith-Magenis Syndrome is a rare chromosomal disorder characterized by abnormalities of the head and facial (craniofacial) area, delays in the acquisition of skills requiring the coordination of mental and muscular activities (psychomotor retardation), mental retardation, speech delays, and/or behavioral abnormalities. Characteristic craniofacial abnormalities may include an abnormally short, broad head (brachycephaly); an abnormally broad, flat midface; a broad nasal bridge; an unusually prominent jaw (prognathism); incomplete closure of the roof of the mouth (cleft palate); and/or malformed, abnormally positioned ears. In addition, most affected individuals experience speech delays that may occur in association with hearing impairment and have an abnormally hoarse, deep voice. Behavioral abnormalities associated with the disorder may include hyperactivity and self-destructive behavior including head-banging, wrist-biting, inserting foreign objects into the nose and ears (polyembolokoilamania), and/or pulling out the fingernails and toenails (onychotillomania). Many individuals with Smith-Magenis Syndrome also experience sleep disturbances including difficulties falling asleep and staying asleep. Smith-Magenis Syndrome occurs due to deletion of a portion of the short arm (p) of chromosome 17 (17p11.2). The chromosomal deletion occurs due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). As initially reported, the syndrome consisted mainly of cleft palate and congenital heart defect. The phenotype was later expanded to include brachycephaly, midfacial hypoplasia, broad nasal bridge, highly arched palate, mandibular prognathism, malformed ears, short hands, mental retardation, and other less constant abnormalities.

Precipitants

None.

Provocation Tests

None.

Diagnostic Procedures

The diagnosis is based on clinical examination. The SMS is characterized by: mental retardation with speech delay; specific behavioral phenotype and major sleep disturbances; mild dysmorphy. The diagnosis is confirmed on high-resolution karyotype with detectable deletion of 17p11.2 and by FISH on chromosome 17. The diagnosis of SMS is usually confirmed through blood tests called chromosome (cytogenetic) analysis and FISH (fluorescence in situ hybridization). People with SMS are born with a small deletion (missing section) of one member of their 17th pair of chromosomes. It is the lack of this specific section, known as 17p11.2, that causes a child to develop the features of SMSThe diagnosis of SMS is confirmed by detection of an interstitial deletion of the short arm of chromosome 17 band p11.2 (del 17p11.2) by G-banded cytogenetic analysis and/or by fluorescence in situ hydridization (FISH). A visible interstitial deletion of chromosome 17p11.2 can be detected in all patients with the common deletion by a routine G-banded analysis provided the resolution is adequate (550 band or higher). It is not uncommon for the deletion to be overlooked particularly when the indication for the cytogenetic study is other than SMS. Molecular cytogenetic analysis by FISH using a DNA-probe specific for the SMS critical region is required in cases of sub-microscopic deletions and/or to resolve equivocal cases.