Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome

J Pediatr. 2001 Jul;139(1):111-6. doi: 10.1067/mpd.2001.115018.


Objective: The objective was to determine the circadian rhythm of melatonin in the Smith-Magenis syndrome (SMS), which causes behavioral problems and sleep disturbance.

Study design: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adolescent
  • Case-Control Studies
  • Child
  • Child Behavior Disorders / genetics*
  • Child, Preschool
  • Chromosomes, Human, Pair 17*
  • Circadian Rhythm*
  • Female
  • Gene Deletion
  • Humans
  • Male
  • Melatonin / metabolism*
  • Mutation
  • Sleep Wake Disorders / genetics*
  • Syndrome


  • Melatonin