title: Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome.
abstract: OBJECTIVE
  The objective was to determine the circadian rhythm of melatonin in the Smith-Magenis syndrome (SMS), which causes behavioral problems and sleep disturbance.
  
  
  METHODS
  Questionnaires, sleep consultations, and sleep diaries were obtained in 20 children with SMS (9 girls, 11 boys aged 4 to 17 years). Actigraphy, electroencephalography, and the circadian variations of plasma melatonin, cortisol, and growth hormone were recorded in 8 patients. Early sleep onset, early sleep offset, and sleep attack indicated sleep disturbance.
  
  
  RESULTS
  All children with SMS had a phase shift of their circadian rhythm of melatonin. Time at onset of melatonin secretion was 6 AM +/- 2 (control group: 9 P.M. +/- 2). Peak time was 12 PM +/- 1 (control group: 3:30 AM +/- 1:30), and melatonin offset was at 8 PM +/- 1 (control group: 6 AM +/- 1). Behavioral problems correlated with the inverted circadian rhythm of melatonin.
  
  
  CONCLUSIONS
  Considering that clock genes mediate the generation of circadian rhythms, we suggest that haploinsufficiency for a circadian system gene mapping to chromosome 17p11.2 may cause the inversion of the circadian rhythm of melatonin in SMS.
authors.affiliation: Department of Genetics and Unité INSERM 393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: De Leersnyder
authors.forename: M C
authors.initials: MC
authors.lastname: De Blois
authors.forename: B
authors.initials: B
authors.lastname: Claustrat
authors.forename: S
authors.initials: S
authors.lastname: Romana
authors.forename: U
authors.initials: U
authors.lastname: Albrecht
authors.forename: J C
authors.initials: JC
authors.lastname: Von Kleist-Retzow
authors.forename: B
authors.initials: B
authors.lastname: Delobel
authors.forename: G
authors.initials: G
authors.lastname: Viot
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics*; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17; D002940:Circadian Rhythm; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D009154:Mutation; D012893:Sleep Wake Disorders / Q000235:genetics*; D013577:Syndrome
chemical_list: D008550:Melatonin