Frequently Asked Questions

The diagnosis of SMS is usually confirmed through a clinical blood test called a chromosome analysis. Diagnosis can be made by specific tests to analyze the chromosomes, including a cytogenetic test (karyotype) and FISH (fluorescence in situ hybridization) or by chromosome microarray analysis (also called CGH). Most people with SMS are born with a small deletion (missing section) of one member of their 17th pair of chromosomes. It is the lack of this specific section, known as 17p11.2, which causes a child to develop the features of SMS.

All deletion cases include deletion of the RAI1 gene. In cases where a deletion is not detected, then sequencing of the RAI1 gene should be considered. About 90% of the cases of SMS are due to deletion, with the remaining 10% due to a mutation that occurs within the RAI1 gene.
Sequencing of RAI1 can be done by different types of genetic tests. Tests that include RAI1 sequencing:

1. Whole Exome Sequencing
2. Panel Genetic Testing
3. RAI1 Sequencing

SMS individuals experience hyperactivity, self-injury (including: head banging; hand biting; picking at skin, sores and nails; pulling off finger- and toenails; inserting foreign objects into ears, nose, or other body orifices), explosive outbursts, prolonged tantrums, destructive and aggressive behavior, excitability and arm hugging/hand squeezing when excited.

Unfortunately the published data about the optimal intervention and behavioral strategies in SMS is limited to anecdotal and experiential findings. Many parents report that the use of psychotropic medications benefit SMS individuals with respect to stabilizing mood swings, decreasing anxiety, increasing attention and/or decreasing hyperactivity. However, no single regimen shows consistent efficacy among the majority of persons with SMS.

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.

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.

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.

Finally, some families with young children have tried enclosed bed systems with much success.

Knowing the cause of your child’s developmental delays can facilitate a family’s access to critical early childhood intervention services such as speech and language therapy, occupational therapy (OT) and/or physical therapy (PT). Early intervention may help program staff identify areas of specific need or risk. For example, some SMS families have benefited from using sign language with their child before his or her speech developed. Additionally, a diagnosis of SMS opens the doors to a network of information and support from professionals and other families dealing with the syndrome.

While no one has studied the life expectancy of individuals with SMS in detail, they appear to have a normal life expectancy. The oldest known person with SMS lived into her late 80’s.

With the appropriate supports, individuals with Smith-Magenis syndrome can attend school, develop their interests, work successfully, and, for some, live more independently. Achieving these outcomes typically requires significant support from families and educational, vocational, and residential services, with early intervention potentially improving long-term outcomes.

New and emerging medications are helping improve quality of life for some individuals with SMS, while ongoing research continues to offer hope for greater independence in the future.