Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome.
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.
De Leersnyder
H
H
Department of Genetics and Unité INSERM 393, Hôpital des Enfants-Malades, Paris, France.
De Blois
M C
MC
Claustrat
B
B
Romana
S
S
Albrecht
U
U
Von Kleist-Retzow
J C
JC
Delobel
B
B
Viot
G
G
Lyonnet
S
S
Vekemans
M
M
Munnich
A
A
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
D008550:Melatonin