Smith-Magenis syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 4, 2017
StartDiseasesSmith-Magenis syndrome

Smith-Magenis syndrome is a developmental disorder which causes a range of cognitive problems and behavioral problems as well as physical abnormalities. It is most often caused by the deletion of a section of chromosome 17.


Definition & Facts

Smith-Magenis syndrome is a developmental disorder that produces a distinctive set of physical features and behaviors. Its name comes from the individuals who discovered it: Ann Smith and Ellen Magenis. The first reports of Smith-Magenis appeared in medical literature in 1982. Smith and Magenis identified patients with the syndrome in 1986, which provided them with additional data. In the years since, researchers have found more people with the condition, which means that clinicians now have a better understanding of the syndrome.

The disorder affects many different parts of the body, and it is estimated to affect one out of every 25,000 people or more. The pattern of physical abnormalities associated with this condition are present at birth. In addition, Smith-Magenis is not inherited in most cases. 

Symptoms & Complaints

Facial features associated with Smith-Magenis syndrome include a broad face with deeply-set eyes that are noticeably further apart than usual. A depressed nasal bridge and a broad forehead are also common. Also common among affected people is hair growth between the eyebrows and a prominent lower jaw.

Patients may have short stature along with scoliosis, which is the curvature of the spine. They may also have short fingers and toes along with flat feet and low muscle tone.

Many people with Smith-Magenis engage in self-harming behavior including head banging and face slapping. Also common is a tendency to insert foreign objects into the ears, nose, and other orifices. 

Varying degrees of cognitive disability and developmental delays occur. These range from delayed speech to delayed potty-training and persistent bedwetting at night. People with this condition may also have delayed motor skills.

People may experience sudden mood shifts along with impulsive, aggressive or attention-seeking behaviors as well as hyperactivity and difficulty paying attentionSleep disorders starting in early childhood that result in daytime sleepiness and difficulty falling asleep at night are symptoms as well. Affected individuals may also wake up multiple times during the night. Sleep problems typically last throughout the individual's life. 

Chronic childhood ear infections are common with the result that many individuals with the condition exhibit hearing impairment. Others may be hypersensitive to specific sounds or frequencies. Myopia, strabismus, and other vision problems are common in people with Smith-Magenis. People with this condition are also more likely to have frequent sinus infections.


Smith-Magenis is the result of genetic material missing from a specific area of chromosome 17. The deletion of the genetic material is sometimes referred to as deletion 17p11.2. While there are multiple different genes in the affected area, the conclusion of many researchers is that one particular gene is responsible for many features of Smith-Magenis: RAI1 gene.

Genes provide instructions that the body needs to create specific proteins required for various functions. A missing gene means that the instructions that that gene would provide are absent. The absence can affect many different areas of the body. Researchers do not yet fully understand all the functions of the RAI1 protein. In most cases, the cause of the alteration to the chromosome that results in Smith-Magenis syndrome is unknown.

In a few instances, it is caused by a balanced translocation in one of the parents' chromosomes. A balanced translocation occurs when two or more chromosomes have pieces break off and those pieces switch places. This results in a greater likelihood of chromosomal abnormalities in the individual's offspring. Along with RAI1, other genes may also be missing. This is why there is variation among the syndrome's features in different people.

About 10 percent of people have a mutation in the RAI1 gene rather than a deletion of the gene. While these people will have many of the Smith-Magenis syndrome symptoms, they are less likely to have short stature or hearing loss. 

Diagnosis & Tests

Diagnosing Smith-Magenis syndrome calls for identification of the characteristic symptoms. Along with undergoing genetic testing, it is important that a patient's family history and medical history be evaluated thoroughly. Upon the discovery of the 17p11.2 deletion or a mutation of the RAI1 gene, the diagnosis of 17p11.2 deletion can be confirmed.

In order to detect missing material on chromosome 17p11.2, a study called G-band analysis can be used. It involves staining the chromosomes to make them more visible for inspection under a microscope.

Researchers can use another test called fluorescence in situ hybridization to find the exact point where the break occurred. This test involves the use of probes marked with fluorescent dye. Researchers use these probes to get a better look at specific parts of the chromosome.

Chromosomal microarray is a newer method that allows for the comparison of an individual's DNA to that of someone without an abnormality. It allows researchers to detect minute alterations. In order to confirm a diagnosis of Smith-Magenis syndrome when a genetic mutation is suspected, researchers may use molecular genetic testing. This method can detect RAI1 mutations.

Treatment & Therapy

Treating Smith-Magenis syndrome requires the combined efforts of multiple specialists including pediatricians, cardiologists, and speech pathologists. In addition, the services of other health care workers may be needed to plan the treatment of an affected child. It is important that treatment begins early to ensure that children with the disorder achieve their potential. Among the services that may be needed are special education and occupational therapy along with speech therapy.

Medications may be used to treat behavioral problems like difficulty sleeping and attention deficit hyperactivity disorder. Therapists may prescribe other psychiatric medications to help with the stabilization of mood swings and to decrease anxiety. It is important to note that there is no single regimen that is deemed effective for most of the people with the disorder. Supplementation of melatonin at bedtime has been beneficial according to some reports. Other anecdotal reports from parents of young children suggest that enclosed beds are effective.

Some individuals with Smith-Magenis syndrome have been able to live semi-independent lives with some support from family and friends. Others may need more intensive care and may live with family or receive care from professional caregivers in a residential facility. 

Prevention & Prophylaxis

At present, Smith Magenis syndrome is unpredictable and is not inherited. There are no known risk factors for the disorder and it appears to occur randomly. This means that there is not a preventive measure that precludes the cause of the condition. Early diagnosis is crucial for enabling a person with the condition to have the highest quality of life.