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Orphanet References OMIM Gene GeneReviews HGMD HGNC
last update : 20-06-2012
Symbol SMS
Location 17p11.2
HGNC id 11113
Name Smith-Magenis syndrome
Other name(s) interstitial deletion of 17p11.2, monosomy 17p11.2
Corresponding gene SMCR , RAI1
Other symbol(s) DEL17P11, del(17)(p11.2p11.2)
Main clinical features
  • distinct cranio-facial features with midface retraction, short philtrum and everted upper lip
  • mental retardation, sleep disturbance, self-injurious and agressive behavior
  • multiple congenital anomalies
  • obesity
  • ophtalmological and otolaryngologic anomalies(>80%), hearing impairment(~70%), cardiac (~40%) and renal (~20-30%) defects
  • Genetic determination chromosomal
    genomic disorder
    Prevalence estimated at 1/25000, probably higher due to under-diagnosis
    Function/system disorder mental retardation
    Type MCA/MR
    Gene product
    Name contiguous gene syndrome, major gene : retinoic acid induced 1; RAI1 is a positive transcriptional regulator of CLOCK (PMID: 22578325)
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency commonly deleted region of 3.5Mb between REPD and REPP in 75 percent of cases, atypical deletion from 1.5 to 9 Mb in others, minimum deletion of ~650kb including RAI1.
        haploinsufficiency in rare patients, mutations in the RAI1 gene, with phenotypic variability
    Remark(s) RAI1 directly regulate circadian rhythms ( PMID: 22578325 )
    Genotype/Phenotype correlations general absence of short stature and lack of visceral anomalies distinguish patients with RAI1 mutations from patients with deletions ; patients with mutations are more likely to exhibit obesity and overgrowth phenotypes. Larger deletion may be associated with cleft palate; Rai1 haploinsufficiency represents a single-gene model of obesity with hyperphagia, abnormal fat distribution and altered hypothalamic gene expression associated with satiety, food intake, behavior and obesity (PMID: 20663924))