Smith-Magenis syndrome
Encyclopedia
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. Smith-Magenis syndrome affects an estimated 1 in 25,000 individuals.
The syndrome is due to an abnormality in the short (p) arm of chromosome 17
and is sometimes called the 17p- syndrome.
, and R. Ellen Magenis
, a pediatrician, medical geneticist and cytogeneticist at the Oregon Health Sciences University.
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 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 may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.
Other symptoms the syndrome can 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
), 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.
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 involved in communication messages between DNA and RNA. The groups led by James Lupski (Baylor College of Medicine) and Sarah Elsea (Virginia Commonwealth University) 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 (eggs or sperm) or in early fetal development. People with Smith–Magenis syndrome most often have no history of the condition in their family.
) analysis and utilize a technique called FISH (fluorescent in situ hybridization
). 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 (ADHD), obsessive-compulsive disorder
(OCD), attention deficit disorder (ADD) and/or mood disorders.
, 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 antagonist acebutolol
can increase concentration, improve sleep and sleep timing and aid in improvement of behaviour. Other medications (such as risperdal) are sometimes used to regulate violent behavior.
Developmental disorder
Developmental disorders occur at some stage in a child's development, often retarding the development. These may include,psychological or physical disorders. The disorder is an impairment in the normal development of motor or cognitive skills that are developed before age 18 in which they are...
that affects many parts of the body. The major features of this condition include mild to moderate mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, distinctive facial features, sleep disturbances, and behavioral problems. Smith-Magenis syndrome affects an estimated 1 in 25,000 individuals.
The syndrome is due to an abnormality in the short (p) arm of chromosome 17
Chromosome 17 (human)
125px|rightChromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 81 million base pairs and represents between 2.5 and 3 % of the total DNA in cells.Identifying genes on each chromosome is an active area of...
and is sometimes called the 17p- syndrome.
Eponym
The eponym Smith–Magenis refers to two workers who described the condition in 1986, namely, Ann C. M. Smith, a genetic counselor at the National Institutes of HealthNational Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, and R. Ellen Magenis
R. Ellen Magenis
R. Ellen Magenis is a distinguished American pediatrician, medical geneticist and cytogeneticist.She was born in Gary, Indiana and received her BA in zoology from Indiana University in Bloomington, Indiana in 1948 and her MD degree from the Indiana University School of Medicine in Indianapolis in...
, a pediatrician, medical geneticist and cytogeneticist at the Oregon Health Sciences University.
Common symptoms
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 typically 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, due to an inverted circadian rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
of melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
.
People with Smith–Magenis syndrome have 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 may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.
Other symptoms the syndrome can include short stature, abnormal curvature of the spine (scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
), reduced sensitivity to pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
and temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
, 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
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
), strabismus
Strabismus
Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
, 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 chromosome 17. Most people with SMS have a deletion of genetic material from a specific region of chromosome 17 (17p11.2). Although this region contains multiple genes, recently researchers discovered that the loss of one particular gene the retinoic acid induced 1 or RAI1RAI1
RAI1 is a transcription factor associated with Smith-Magenis syndrome. It is known as retinoic acid induced 1.-External links:*...
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 involved in communication messages between DNA and RNA. The groups led by James Lupski (Baylor College of Medicine) and Sarah Elsea (Virginia Commonwealth University) 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 (eggs or sperm) 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 (cytogeneticCytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...
) analysis and utilize a technique called FISH (fluorescent in situ hybridization
Fluorescent in situ hybridization
FISH is a cytogenetic technique developed by biomedical researchers in the early 1980s that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high...
). 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
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
(OCD), attention deficit disorder (ADD) 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 therapyPhysical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
, occupational therapy
Occupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
and speech therapy. Support is often required throughout an affected person's lifetime.
Medication is often used to address some symptoms. Melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
supplements and trazodone
Trazodone
Trazodone is an antidepressant of the serotonin antagonist and reuptake inhibitor class. It is a phenylpiperazine compound...
are commonly used to regulate sleep disturbances. In combination with exogenous melatonin, blockade of endogenous melatonin production during the day by the adrenergic antagonist acebutolol
Acebutolol
Acebutolol is a beta blocker for the treatment of hypertension and arrhythmias.-Pharmacology:Acebutolol is a cardioselective beta blocker with ISA...
can increase concentration, improve sleep and sleep timing and aid in improvement of behaviour. Other medications (such as risperdal) are sometimes used to regulate violent behavior.
External links
- PRISMS — Parents and Researchers Interested in Smith-Magenis Syndrome
- http://www.smith-magenis.dk - Denmark