Smith–Magenis Syndrome has features including intellectual disability, facial abnormalities, difficulty sleeping, and numerous behavioral problems such as self-harm. Smith–Magenis syndrome affects an estimated between 1 in 15,000 to 1 in 25,000 individuals. It is a microdeletion syndrome characterized by an abnormality in the short arm of chromosome 17 and is sometimes called the 17p- syndrome.
Signs and symptoms
Facial features of children with Smith–Magenis syndrome include a broad and square face, deep-set eyes, large cheeks, and a prominent jaw, as well as a flat nose bridge. Eyes tend to be deep-set and appear close together there is also a slant upwards. Eyebrows are heavy with lateral extension. The mouth is the most noticeable feature, both upper and lower lips are full, the mouth is wide. The mouth curves downwards and the upper lip curves outwards, due to a fleshy philtrum. These facial features become more noticeable as the individual ages, as Mandible growth outstrips that of the maxilla leading to a clear midface hypoplasia. There is also a mild brachycephaly. 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, due to an inverted circadian rhythm of melatonin. People with Smith–Magenis syndrome have engaging personalities, but all also have a lot of behavioral problems. These behavioral problems include frequent temper tantrums, meltdowns and outbursts, aggression, anger, fidgeting, compulsive behavior, anxiety, impulsiveness, and difficulty paying attention. Self-harm, 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 may also compulsively lick their fingers and flip pages of books and magazines, as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia. Other symptoms can include short stature, abnormal curvature of the spine, 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, strabismus, and other problems with vision. Heart and kidney defects also have been reported in people with Smith–Magenis syndrome, though they are less common.
Genetics
Smith–Magenis syndrome is a chromosomal condition related to low copy repeats of specific segments of chromosome 17. Most people with SMS have a deletion of genetic material from a specific region of chromosome 17. Although this region contains multiple genes, recently researchers discovered that the loss of one particular gene the retinoic acid induced 1 or RAI1 is responsible for most of the characteristic features of this condition. Also, other genes within the chromosome 17 contribute to the variability and severity of the clinical features. 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 deletions and mutations lead to the production of an abnormal or nonfunctional version of the RAI1 protein. RAI1 is a transcription factor that regulates the expression of multiple genes, including several that are involved in controlling circadian rhythm, such as CLOCK. The groups led by James Lupski and Sarah Elsea are in the process of studying the exact function of this gene in relation to Smith Magenis Syndrome. SMS is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells or in early fetal development. People with Smith–Magenis syndrome most often have no history of the condition in their family.
Diagnosis
SMS is usually confirmed by blood tests called chromosome analysis and utilize a technique called FISH. The characteristic micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results. The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion. However, further testing is required for variations of Smith–Magenis syndrome that are caused by a mutation of the RAI1 gene as opposed to a deletion. Children with SMS are often given psychiatric diagnoses such as autism, attention deficit/hyperactivity disorder, obsessive-compulsive disorder, attention deficit disorder and/or mood disorders.
Treatment
Treatment for Smith–Magenis syndrome relies on managing its symptoms. Children with SMS often require several forms of support, including physical therapy, occupational therapy and speech therapy. Support is often required throughout an affected person's lifetime. Medication is often used to address some symptoms. Melatonin supplements and trazodone are commonly used to regulate sleep disturbances. In combination with exogenous melatonin, blockade of endogenous melatonin production during the day by the adrenergic antagonistacebutolol can increase concentration, improve sleep and sleep timing and aid in improvement of behaviour. Other medications are sometimes used to regulate violent behavior.
