The Smith-Magenis Syndrome Guide: A simple To Follow Overview Of The Symptoms, Associated Genes, Tests, Treatment And Patient Support.

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Smith-Magenis Syndrome: Symptoms and Description

Smith–Magenis syndrome is a complex neurobehavioral, developmental disorder that takes place due to mutations and interstitial deletions associated with chromosome 17p11.2 region which encodes the retinoic acid-induced 1 (RAI1) gene. Recent studies have proven that haploinsufficiency of the retinoic acid-induced 1 (RAI1) gene located on chromosome 17p11.2 is actually responsible for this disorder.

The typical symptoms of Smith-Magenis syndrome include unique facial features which progress with age, developmental delays, cognitive impairment and many behavior anomalies. Babies show feeding issues, failure to thrive, hypotonia, hyporeflexia, excessive periods of napping with need to be forcibly awakened at feeding times and general lethargy. Most patients have mild-to-moderate degrees of mental retardation.

In Smith-Magenis syndrome there are disturbed sleeping patterns, stereotypes as well as non-adaptive and self-injurious behavior patterns seen after 18 months of age and which progress into adulthood. Both kids as well as adults with Smith-Magenis syndrome show lack of attention, hyperactivity, frequent temper tantrums, attention seeking and impulsive behavior, disobedience, aggression, and self-injurious behaviors (SIB) like self-hitting, self-biting, using sharp foreign objects on body orifices (known in medical terms as polyembolokoilamania), and pulling of nails (onychotillomania).

Two very typical behaviors seen in Smith-Magenis syndrome patients are the spasmodic upper-body squeeze or “self-hug” and finger lick and page flipping (“lick and flip”).

What Causes Smith-Magenis Syndrome: The Genetic Aspects

Smith-Magenis syndrome is caused by either mutations or deletions in chromosome 17. Over 90 percent of the people who have this disorder have a fluorescent in situ hybridization (FISH) detectable 17p11.2 micro-deletion ranging in size from 1.5 to 9 Mb, while about 10% have a mutation in RAI1 gene. The loss of this particular gene, RAI1, in every cell causes most of the characteristic symptoms seen in this disorder.

It is indicated that loss of other genes in the deleted region is the reason for the variations in the symptoms of Smith-Magenis syndrome patients. The RAI1 gene encodes instructions for the production of a protein whose function still unknown. Mutations in one copy of this gene cause the production of a nonfunctional version of the protein which causes the physical, mental, and behavioral issues seen in Smith-Magenis syndrome.

Most incidences of this order are de novo and complicated familial chromosomal rearrangements causing deletion (17) (p11.2) are very rare. If parental chromosome analysis done by karyotype tests comes as normal, the risk to future siblings is less than 1%. A tiny recurrence risk is possible if there is evidence of germline mosaicism in the family genetic make-up. If a parent belonging to the proband shows balanced chromosomal rearrangement, at-risk family members should be tested using both chromosome analysis and FISH.

Diagnosis, Treatment And Patient Management

The diagnosis of Smith-Magenis syndrome is confirmed by identifying an interstitial deletion of 17p11.2 through G-banded cytogenetic analysis, by fluorescence in situ hybridization (FISH), or by use of array genomic hybridization (aGH). Molecular cytogenetic analysis using either FISH or aGH via a DNA probe specific for the Smith-Magenis syndrome critical region is necessary in patients who have micro- deletions. Molecular genetic testing for the RAI1 gene known is also used in patients in whom a FISH-detectable deletion has been excluded after testing already.

Although there are really no cures for Smith-Magenis syndrome yet, treatment of kids with acebutolol, a selective beta-1-adrenergic antagonist, have shown significant improvement of SIB behavior, higher concentration, delayed sleep onset, more sleep and delayed waking in experimental studies.

Management takes many forms like therapy for sleep disturbance, early intervention programs for special education and vocational training, speech and behavioral therapy and constant surveillance through annual multidisciplinary evaluations, medical testing recommended by the doctor and neurodevelopmental assessments and pediatric consultations to monitor the progression of the disorder. Respite care and psychosocial support for family members and caregivers of patients with Smith-Magenis syndrome is very essential as the caregivers get mentally and physically exhausted.


  1. ‘Smith-Magenis syndrome.’ (2010). Retrieved on October 21st, 2010 from Genetics Home Reference, A service of the U.S. National Library of Medicine:

  1. ‘MIM ID #182290 SMITH-MAGENIS SYNDROME; SMS.’ (2010). Retrieved on October 21st, 2010 from OMIM (Online Medelian Inheritance in Man), NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine):

  1. Elsea, H. S & Girirajan, S. (2007). Smith–Magenis syndrome. European Journal of Human Genetics (2008) 16; 412–421.

  2. ‘Smith–Magenis syndrome.’ (2010). GeneReviews. Retrieved on October 21st, 2010 from NIH, USA: