Treatment of Smith-Magenis syndrome as an advanced sleep phase syndrome
We read with attention and interest the eLetter by Been et al. We would like to reply.
We agree with the author that Smith-Magenis syndrome (SMS) may be may be an extremely advanced sleep phase syndrome. The definition of this advanced sleep phase syndrome is based actually on clinical evaluation and melatonin dosages. A mutation of Perclock gene was found in families with familial advances sleep phase syndrome, but there is no evidence of this mutation in non familial cases and Per gene is not deleted in SMS. Following this hypothesis, it is of interest to try a treatment by melatonin in the morning to reset the melatonin secretion of this hormone in SMS. That is what the authors of the letter did, with success. Meanwhile, there is only one case studied, and they have no objective proof of the results, such as plasmatic melatonin dosages or polysomnography or actimetry recordings.
In our study, the main purpose was to act on the symptoms and to blockade the endogenous melatonin secretion to improve day behaviour (hyperactivity, tantrums, excessive daytime sleepiness) and then reset the clock by adding melatonin in the evening. Our study in 9 children is confirmed by melatonin dosages and actimetry recordings. The mechanism of melatonin phase shift in SMS is not yet known, and treatment approach acting on the mechanism as L. Bok did is very interesting and the good results he obtained encourage further studies. In the same order we could imagine using phototherapy in the morning in SMS. The difficulty is to have large series of patients of this rare disorder, and to make double-blind series if possible, with bioethical approved protocols.
(1) Been J et al. Improvement of sleep disturbances and behaviour in Smith-Magenis syndrome with morning melatonin [electronic response to de Leersnyder et al. Beta-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome] jmedgenet.com 2003http://jmg.bmjjournals.com/cgi/eletters/40/1/74#30