Inverted Melatonin Cycle in Smith-Magenis Syndrome

Inverted Melatonin Cycle in Smith-Magenis Syndrome

What is Smith-Magenis Syndrome?

Smith-Magenis Syndrome (SMS) is a neurodevelopmental disorder caused by a deletion of a portion of chromosome 17.

The prevalence of SMS is 1 in 25,000 live births and are all new mutations, meaning nothing is inherited. Smith-Magenis Syndrome has a number of distinct characteristics, including specific facial features, eye abnormalities, speech delay, a hoarse deep voice, short stature with failure to thrive and peripheral neuropathy. All SMS patients have a certain degree of developmental delay and may have lower IQ scores.

Behavioral problems associated with Smith-Magenis Syndrome include aggression, self-injury, low sensitivity to pain, repetitive behavior, tamper tantrums, impulsivity and hyperactivity with attention deficit. A SMS diagnosis is based on clinical features and are confirmed by a high-resolution (chromosome) karyotype.

Sleep disturbances

Severe sleep disturbances and an unusual circadian rhythm are important features of this disorder. The symptoms of sleep disturbance in the majority of SMS patients include early sleep onset (right after dinner time), repeated awakenings during the night and early awakenings (between 4 and 5AM), regardless of sex or age of the child. The average sleep per child per night is around 7.5 hours and this can have a great effect on the child and other family members.

Normally, melatonin synthesis peaks in the middle of the night and gradually wears off toward the morning. In Smith-Magenis Syndrome, the circadian clock seems to be inverted, with no melatonin production during the night and 2 melatonin “peaks“, one in mid-morning and the second right around dinnertime.

This inverted sleep-wake cycle in SMS patients leads to morning tiredness, tamper tantrums and daytime naps. Also, “sleep attacks” occur often at the end of the day, with kids falling asleep at the dinner table. The nighttime awakenings force most parents to device ways to keep their child in their bedroom, locking doors, moving furniture and keeping stuff locked up in the kitchen, all to avoid accidents.

How can the inverted rhythm of melatonin secretion in SMS be treated?

The deletion involved in Smith-Magenis Syndrome could include an important “clock” gene, that when deleted causes an inversion of melatonin secretion. Behavior and sleep disturbances associated with SMS are extremely severe and difficult to manage. Many SMS patients were given medications (including psychiatric drugs), that failed to work over time.

The study that De Leersnyder describes, attempted to treat the inverted rhythm of melatonin synthesis by giving SMS patients a timed-release melatonin tablet at night and a beta-adrenergic antagonist (beta-blocker) during the day, that reduces the production of melatonin. This treatment, improved daytime behavior and sleep patterns in all SMS patients. Patients were also able to focus better and tantrums were less severe and less frequent.

It is possible that timed-release melatonin may be beneficial to children with autism, who have sleep disturbances. This, of course, has to be discussed with your child’s pediatrician.

Natural ways to suppress melatonin production during the day.

  • Chamomile (fresh tea) has been reported to be able to decrease melatonin
  • Magnesium is also suggested to have a negative effect on melatonin synthesis


De Leersnyder, H. (2006) Inverted rhythm of melatonin secretion in Smith–Magenis syndrome: from symptoms to treatment. Trends Endocrin. Metabol. 17: 291-298.

Smith, A.C.M. et al. (1982) Deletion of the 17 short arm in two patients with facial clefts. Am. J. Med. Genet. 34 (Suppl. A): 410.

Shelley, B.P. and Robertson, M.M. (2005) The neuropsychiatry and multisystem features of the SmithMagenis syndrome: a review. J. Neuropsychiatry Clin. Neurosci. 17: 91–97.

Smith, A.C.M. et al. (1998) Sleep disturbance in Smith–Magenis syndrome (del 17p11.2). Am. J. Med. Genet. 81: 186–191.

De Leersnyder, H. et al. (2001) Inversion of the circadian rhythm of melatonin in the Smith–Magenis syndrome. J. Pediatr. 139, 111–116.

De Leersnyder, H. et al. (2003) Beta-1-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith–Magenis syndrome. J. Med. Genet. 40: 74–78.

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