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 intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems.

Most people 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 more distinctive in later childhood and adulthood. Dental abnormalities are also common in affected individuals.

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 affectionate, 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 vision problems. Although less common, heart and kidney defects also have been reported in people with Smith-Magenis syndrome.

Smith-Magenis syndrome affects at least 1 in 25,000 individuals worldwide. Researchers believe that many people with this condition are not diagnosed, however, so the true prevalence may be closer to 1 in 15,000 individuals.

Smith-Magenis syndrome is 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, in each cell 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. Although these individuals have many of the major features of the condition, they are less likely than people with a chromosomal deletion to have short stature, hearing loss, and heart or kidney abnormalities. The RAI1 gene provides instructions for making a protein whose function is unknown. Mutations in one copy of this gene lead to the production of a nonfunctional version of the RAI1 protein or reduce the amount of this protein that is produced in cells. Researchers are uncertain how changes in this protein result in the physical, mental, and behavioral problems associated with Smith-Magenis syndrome.

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. Most often, people with Smith-Magenis syndrome have no history of the condition in their family.