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Smith-Magenis syndrome

Thursday 20 November 2003

Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation disorder characterized by distinct craniofacial features and neurobehavioral abnormalities usually associated with an interstitial deletion in 17p11.2.

Smith-Magenis syndrome (SMS) is rare (prevalence 1 in 25 000) and is associated with psychomotor delay, a particular behavioural pattern and congenital anomalies.

SMS is often due to a chromosomal deletion of @<@4 Mb at the 17p11.2 locus, leading to haploinsufficiency of numerous genes.

Mutations of one of these gemes, RAI1, seems to be responsible for the main features found with heterozygous 17p11.2 deletions.

This contiguous gene syndrome is caused by an interstitial deletion of 17p11.2 invloving genes TOP3 (topoisomerase III) and RAI1 gene (MIM.607642).


- brachycephaly
- midface hypoplasia
- broad face
- hearing loss (conductive and/or sensorineural)
- broad nasal bridge
- cardiac malformations (congenital heart defects)
- renal malformaions (structural renal anomalies)
- scoliosis
- brachydactyly

- neuropsychiatric disorders

  • speech delay
  • mental retardation (IQ 20-78)
  • behavioral problems
  • self-destructive behavior
  • onychotillomania (pulling out nails)
  • wrist-biting
  • head-banging
  • polyembolokoilamania (insertion of foreign bodies into body orifices)
  • sleep disturbance
  • hyperactivity
  • decreased pain sensitivity
  • decreased/absent deep tendon reflexes

- peripheral neuropathy
- structural brain abnormalities
- hoarse voice


- RAI1 or TOP3 germline mutations


- Andrieux J, Villenet C, Quief S, Lignon S, Geffroy S, Roumier C, de Leersnyder H, de Blois MC, Manouvrier S, Delobel B, Benzacken B, Bitoun P, Attie-Bitach T, Thomas S, Lyonnet S, Vekemans M, Kerckaert JP. Genotype phenotype correlation of 30 patients with Smith-Magenis syndrome (SMS) using comparative genome hybridisation array: cleft palate in SMS is associated with larger deletions. J Med Genet. 2007 Aug;44(8):537-40. PMID: 17468296

- Yan J, Bi W, Lupski JR. Penetrance of craniofacial anomalies in mouse models of smith-magenis syndrome is modified by genomic sequence surrounding rai1: not all null alleles are alike. Am J Hum Genet. 2007 Mar;80(3):518-25. PMID: 17273973

- Bi W, Saifi GM, Girirajan S, Shi X, Szomju B, Firth H, Magenis RE, Potocki L, Elsea SH, Lupski JR. RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion Smith-Magenis syndrome. Am J Med Genet A. 2006 Oct 13; PMID: 17041942