Smith-Magenis syndrome
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).
Synopsis
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
Etiology
RAI1 or TOP3 germline mutations
References
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