title: Circadian rhythm disorder in a rare disease: Smith-Magenis syndrome.
abstract: Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome, caused by interstitial deletion of chromosome 17p11.2. The SMS phenotype include distinctive facial features, developmental delay and neurobehavioral abnormalities. The patients present major sleep disturbances ascribed to a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Treatment with morning beta-blockers and evening melatonin reinstated a normally timed melatonin circadian rhythm, improved daytime behavior and restored normal sleep habits, resulting in a greatly improved quality of life for both SMS patients and their family. SMS is the demonstration of biological basis for sleep disorder in a genetic disease. Considering that clock genes mediate generation of circadian rhythms, we suggest that haploinsufficiency for a circadian system gene mapping to chromosome 17p11.2 may cause the inversion of circadian rhythm in SMS.
authors.affiliation: Department of Genetics, Hospital Robert Debré, 75019 Paris, France. deleers@club-internet.fr
authors.forename: Hélène
authors.initials: H
authors.lastname: De Leersnyder
authors.forename: Bruno
authors.initials: B
authors.lastname: Claustrat
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
mesh_terms: D002648:Child; D002940:Circadian Rhythm / Q000502:physiology*; D002658:Developmental Disabilities / Q000503:physiopathology*; D030342:Genetic Diseases, Inborn / Q000503:physiopathology*; D006801:Humans; D008550:Melatonin / Q000235:genetics / Q000502:physiology*; D009422:Nervous System Diseases / Q000503:physiopathology*; D010870:Pineal Gland / Q000503:physiopathology; D013577:Syndrome
chemical_list: D008550:Melatonin