Sleep
LIVING WITH SMS
Sleep
As infants, persons with Smith-Magenis syndrome 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?
Treatment
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.
Sleep Patterns and Habits in SMS Individuals
What causes the sleep problems in SMS individuals? Are there known treatments?
Living with SMS
BEHAVIOR
SPEECH & LANGUAGE
SLEEP
MEDICAL MANAGEMENT & TREATMENT
MEDICATION
GUARDIANSHIP & FINANCIAL PLANNING
SLEEP & SMS
Known Causes and Treatments
“Efforts to understand sleep patterns and habits in SMS individuals have led to the confirmation of an unusual inverted circadian rhythm of melatonin. Research to determine the underlying cause for this disrupted sleep cycle has only just begun. Therapeutic management of the sleep disorder in SMS remains a challenge for physicians and parents. Reports of therapeutic benefit from melatonin suggest general improvement of sleep without major adverse reactions. However, melatonin dispensed over-the-counter is not regulated in the U.S. by the FDA; thus, dosages prepared by different companies may not be comparable. No formal melatonin treatment trials have been conducted. A parent-monitored trial of four to six weeks on low-dose (3 mg) melatonin may be worth considering; continue with melatonin only if your notes indicate an improvement of sleep and/or behavior. It is important to note that high doses (>5 mg) of exogenous oral melatonin may remain in the body into the next morning, and may exacerbate daytime sleepiness and diminish daytime vigilance and alertness.”
“Some families have had limited success with sleep medications other than melatonin. A single open trial of nine patients with SMS treated with oral beta blocker (Acebutolol 10 mg/kg) and melatonin reported suppression of melatonin peaks and subjectively improved behavior [de Leersnyder et al 2001]. While this work is exciting and promising, more research needs to be done.”
“Finally, some families with young children have tried enclosed bed systems with much success.”
HETLIOZ® capsules are indicated for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older (1).
HETLIOZ ™ LQ oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in pediatric patients 3 years to 15 years of age (1).
The effectiveness of HETLIOZ® in the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) was established in a 9-week, double-blind, placebo-controlled cross-over study in adults and pediatric patients with SMS (Study3; NCT 02231008). Patients 16 years of age and older received HETLIOZ® 20 mg capsules, and pediatric patients 3 years to 15 years of age received a weight –based dose of oral suspension.
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 The Safety Sleeper 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.