Smith-Magenis Syndrome

Clinical Characteristics
Ocular Features: 

Ocular abnormalities have been found in the majority of patients.  Microcornea, myopia, strabismus and iris dysplasia are the most common.  Rare patients have iris colobomas or correctopia.  The eyes appear deep-set and lid fissures are upward slanting.

Systemic Features: 

The facial features are considered to be distinctive, characterized by a broad, square face, prominent forehead, broad nasal bridge, and midface hypoplasia.  These and other features appear more pronounced with age as in the size of the jaw which is underdeveloped in infancy and eventually becomes prognathic.  Most patients have developmental delays, speech and motor deficits, cognitive impairments and behavioral abnormalities.  Hypotonia, hyporeflexia, failure to thrive, lethargy, and feeding difficulties are common in infants.  Older individuals have REM sleep disturbances with self-destructive behaviors, aggression, inattention, hyperactivity, and impulsivity.  Short stature, hypodontia, brachydactyly, hearing loss, laryngeal anomalies, and peripheral neuropathy are common. Seizures are uncommon.


Most patients (90%) with the Smith-Magenis syndrome have interstitial deletions in the short arm of chromosome 17 (17p11.2).  However, it is included here since a few have heterozygous molecular mutations in the RAI1 gene which is located in this region.  While there is considerable phenotypic overlap, individuals with chromosomal deletions have the more severe phenotype as might be expected.  For example, those with RAI1 mutations tend to be obese and are less likely to exhibit short stature, cardiac anomalies, hypotonia, hearing loss and motor delays than seen in patients with a deletion in chromosome 17.  However, the phenotype is highly variable among patients with deletions depending upon the nature and size of the deletion.

The retinoic acid induced 1 gene (RAI1) codes for a transcription factor whose activity is reduced by mutations within it.

Familial cases are rare and reproductive fitness is virtually zero.  If parental chromosomes are normal, the risk for recurrence in sibs is less than 1%.  Males and females are equally affected.

Treatment Options: 

Medical monitoring, psychotropic medications and behavioral therapies are all useful.  Special education and vocational training may be helpful for those less severely affected.

Article Title: 


Carmona-Mora P, Canales CP, Cao L, Perez IC, Srivastava AK, Young JI, Walz K. RAI1 Transcription Factor Activity Is Impaired in Mutants Associated with Smith-Magenis Syndrome. PLoS One. 2012;7(9):e45155. doi: 10.1371/journal.pone.0045155. Epub 2012 Sep 18.

PubMedID: 23028815

Edelman EA, Girirajan S, Finucane B, Patel PI, Lupski JR, Smith AC, Elsea SH. Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases. Clin Genet. 2007 Jun;71(6):540-50.

PubMedID: 17539903

Girirajan S, Elsas LJ 2nd, Devriendt K, Elsea SH. RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. J Med Genet. 2005 Nov;42(11):820-8.

PubMedID: 15788730

Greenberg F, Lewis RA, Potocki L, Glaze D, Parke J, Killian J, Murphy MA, Williamson D, Brown F, Dutton R, McCluggage C, Friedman E, Sulek M, Lupski JR. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am J Med Genet. 1996 Mar 29;62(3):247-54.

PubMedID: 8882782