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.