Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Smith-Magenis Syndrome (SMS) [Q93]

OMIM number: 182290

Dr. med. Imma Rost

Scientific Background

The Smith-Magenis syndrome (SMS) is marked by a developmental delay, combined with typical behavioural patterns and discreet physical features such as brachycephaly, midface hypoplasia, broad nasal bridge, an everted upper lip with a ‘tented’ appearance with short philtrum, brachydactylia as well as constrictions in the lower arm area in infants and toddlers. Frequently, the voice is deep and hoarse. Up to 70% of all patients suffer from a hearing impairment due to chronic ear infections (80-90%). Approx. 30% have congenital heart and/or kidney defects. Malpositions of the feet are common. Approx. 50% have a myopia, occasionally resulting in retinal detachment. Temper tantrums, self-injury and severe sleeping problems are typical for SMS and can represent a considerable stress factor for the families. Many children seem to be musically talented; most of them have good computer skills which can be used for individual support and encouragement. The frequency is 1:15,000 to 1:25,000. However, SMS is probably underdiagnosed.

In 90% of all cases, the cause is a microdeletion with varying size (1.5 to 9 mb, usually approx. 3.7 mb) of the short arm of chromosome 17 (17p11.2) that includes the RAI1 gene. In 10% of all cases a mutation in the RAI1 gene can be found. The RAI1 gene causes most of the signs and symptoms of SMS; another 13 genes in the region of the deletion modify the level of severity (contiguous gene syndrome). The microdeletion or mutation is usually de novo; therefore, the recurrence risk is low if a parental structural chromosomal abnormality in chromosome 17 or a rare parental mosaic for a RAI1 mutation has been ruled out. Large deletions can be detected by conventional chromosome analysis; the more frequently occurring small ones by FISH analysis.