As infants, persons with SMS are generally described by their parents as happy, easy going babies who are complacent, sometimes lethargic, and often sleeping more than might be expected (Smith and Gropman, 2000). The sleep disturbance may go unrecognized in infancy. However, new evidence suggests that the sleep disturbance begins as early as one year of age and continues into adulthood,. Children with SMS demonstrate shortened sleep cycles for their age, with frequent awakenings (arousals) during the night, early sleep offset (5:30-6:30 AM) and increased daytime sleepiness (napping) during daylight hours. The sleep disturbance in SMS is chronic, occurring almost every night, thereby impacting the child’s daytime behaviors, as well as family and school life.
Efforts to understand sleep patterns and habits in SMS individuals have led to the confirmation of an unusual inverted circadian rhythm of melatonin.
Melatonin is a hormone secreted by the pineal gland that helps control body rhythms and sleep wake cycles in relation to daylight. The timing of melatonin release is controlled by the internal circadian “clock” that is located in a part of the brain called the suprachiasmatic nucleus, or SCN. Throughout the plant and animal kingdom, melatonin levels rise in the evening, peak during the night, and then fall to very low values during the day. In addition, light that enters the eye at night suppresses the nocturnal rise of melatonin. Based on research conducted by Dr. Lorraine Potocki at Baylor College of Medicine (Potocki et. al., 1997; 2000) and confirmed later in France by Dr. Helene DeLeersnyder (DeLeersnyder et. al., 2001), this normal rhythm or cycle of melatonin does not appear to be the case in persons with SMS. Future research to understand this conundrum must answer two critical questions: (1) why is the circadian rhythm of melatonin inverted? and (2) why doesn’t light suppress melatonin levels like it does in other species?
The therapeutic management of the sleep disorder in SMS remains a challenge for physicians and parents. On December 1, 2020, the U.S. Food and Drug Administration (FDA) approved HETLIOZ® (tasimelteon) capsule and liquid formulations for the treatment of adults and children, respectively, with nighttime sleep disturbances associated with Smith-Magenis Syndrome (SMS). HETLIOZ® (tasimelteon) is a melatonin receptor agonist. HETLIOZ® has been granted market authorization by the U.S. Food and Drug Administration and the European Medicines Agency. For full U.S. Prescribing Information for HETLIOZ®, including indication and Important Safety Information, visit www.hetlioz.com.
Melatonin dispensed over-the-counter is not regulated in the U.S. by the FDA; thus, dosages may not be exact. No formal melatonin treatment trials have been conducted. Some parents report that melatonin taken at bedtime provides general improvement of sleep without reports of major adverse reactions. A monitored trial of four to six weeks on low-dose (3 mg) melatonin may be worth considering in individuals with major sleep disturbance. Consultation with a sleep specialist or your pediatrician is recommended before using doses above 3 mg. Doses above 5 mg taken in the evening can remain in the body into the next day and produce sleepiness and decreased alertness.
Some families have tried an enclosed bed system with much success. ABRAM’S NATION, a company that makes enclosed beds, is well recommended by parents of an SMS child – see https://safetysleeper.com/collections/fully-enclosed-beds for more information on their enclosed beds.
Sleep histories are important for documenting developmental changes in sleep/wake schedules and respiratory function. A sleep diary (a detailed hourly record of an individual’s actual sleep-wake pattern for a week or more) may prove helpful in documenting sleep/wake schedules. Evidence of sleep-disordered breathing warrants polysomnogram and overnight sleep study to evaluate for obstructive sleep apnea. For help finding a sleep clinic in your area, check out this resource from the American Academy of Sleep Medicine.