The Smith-Magenis syndrome [del(17)p11.2]: Clinical review and molecular advances

The Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation syndrome associated with a deletion of chromosome 17p11.2. Since the recognition of this disorder as a clinical entity in 1982, the phenotypic features of SMS have been well described. Unfortunately, the often subtle physical and chromosomal findings of SMS may preclude the diagnosis in some affected individuals. This article offers a comprehensive review of more than 100 SMS patients whose cases have been reported, including details of the more recently studied clinical aspects of SMS. SMS has been postulated to be a contiguous gene deletion syndrome. Currently, only a few genes have been mapped to the SMS critical region. Further research (including genotype-phenotype correlation) is needed to identify the gene or genes that, when deleted, cause this disorder. Although the molecular etiology of SMS is unknown, recent investigations have identified multiple repetitive sequences within the SMS region. As described in other human disorders, repetitive sequences may be involved in homologous recombination and cause deletion. The advances in the molecular dissection of the SMS region are described, and hypotheses regarding the molecular mechanisms of SMS are offered. Parallels are made between the SMS region and other regions in the human genome where the molecular etiologies of diseases have been elucidated.