Smith-Magenis Syndrome

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What is Smith-Magenis syndrome?

Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate mental retardation, distinctive facial features, sleep disturbances, and behavioral problems.

Most children with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become coarser and more distinctive in later childhood and adulthood.

Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, typically beginning early in life. Affected people may be very sleepy during the day, but have trouble falling asleep and awaken several times each night.

People with Smith-Magenis syndrome have endearing, engaging personalities, but most also have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very common. Repetitive self-hugging is a behavioral trait that may be unique to Smith-Magenis syndrome. People with this condition also compulsively lick their fingers and flip pages of books and magazines (a behavior known as lick and flip).

Other signs and symptoms of Smith-Magenis syndrome include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and other problems with vision. Heart and kidney defects also have been reported in people with Smith-Magenis syndrome, though they are less common.

How common is Smith-Magenis syndrome?

Smith-Magenis syndrome affects at least 1 in 25,000 individuals and has been reported in more than 100 people worldwide.

What are the genetic changes related to Smith-Magenis syndrome?

Smith-Magenis syndrome is a chromosomal condition related to chromosome 17.

Mutations in the RAI1 gene cause Smith-Magenis syndrome.

Most people with Smith-Magenis syndrome have a deletion of genetic material from a specific region of chromosome 17. Although this region contains multiple genes, researchers believe that the loss of one particular gene, RAI1, is responsible for most of the characteristic features of this condition. The loss of other genes in the deleted region may help explain why the features of Smith-Magenis syndrome vary among affected individuals.

A small percentage of people with Smith-Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. These mutations lead to the production of an abnormal or nonfunctional version of the RAI1 protein. The function of the RAI1 protein is unknown, and researchers are uncertain how a loss of this protein results in the physical, mental, and behavioral problems associated with Smith-Magenis syndrome.

Can Smith-Magenis syndrome be inherited?

Smith-Magenis syndrome is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. People with Smith-Magenis syndrome most often have no history of the condition in their family.

Source: National Institutes of Health

Research data from Baylor College of Medicine update understanding of smith-magenis syndrome genetics

"We generated an additional strain with a 1-Mb deletion intermediate in size between the two described above. Remarkably, the penetrance of its craniofacial anomalies in the mixed background was between those of Df(11)17 and Df(11)17-1. We further analyzed the deletion mutations and the Rai1(-/+) allele in a pure C57BL/6 background, to control for nonlinked modifier loci. The penetrance of the craniofacial anomalies was markedly increased for all the strains in comparison with the mixed background. Mice with Df(11)17 and Df(11)17-1 deletions had a similar penetrance, suggesting that penetrance may be less influenced by deletion size, whereas that of Rai1(-/+) mice was significantly lower than that of the deletion strains. We hypothesize that potential trans-regulatory sequence(s) or gene(s) that reside within the 590-kb genomic interval surrounding Rai1 are the major modifying genetic element(s) affecting the craniofacial penetrance. Moreover, we confirmed the influence of genetic background and different deletion sizes on the phenotype," wrote J. Yan and colleagues, Baylor College of Medicine.

The researchers concluded: "The complicated control of the penetrance for one phenotype in SMS mouse models provides tools to elucidate molecular mechanisms for penetrance and clearly shows that a null allele caused by chromosomal deletion can have different phenotypic consequences than one caused by gene inactivation."

Yan and colleagues published their study in The American Journal of Human Genetics (Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. The American Journal of Human Genetics, 2007;80(3):518-25).

For more information, contact J. Yan, Baylor College of Medicine, Dept. of Molecular and Human Genetics, Houston, TX 77030 USA.

Publisher contact information for the The American Journal of Human Genetics is: University Chicago Press, 1427 E 60th St., Chicago, IL 60637-2954, USA.

Keywords: United States, Houston, Smith-Magenis Syndrome Genetics, Genetics, Smith-Magenis Syndrome.

This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.