Rare Gastroenterology News

Disease Profile

Smith-Magenis syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q93.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SMS; Chromosome 17p11.2 deletion syndrome

Categories

Chromosome Disorders; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases;

Summary

Smith-Magenis syndrome (SMS) 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 SMS have a deletion of genetic material in each cell 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 features of the condition. In most of these cases, the deletion is not inherited, occurring randomly during the formation of eggs or sperm, or in early fetal development.[1] In rare cases, the deletion is due to a chromosomal balanced translocation in one of the parents. In about 10% of cases, SMS is caused by a mutation in the RAI1 gene. These mutations may occur randomly, or may be inherited from a parent in an autosomal dominant manner. Treatment for SMS depends on the symptoms present in each person.[2]

Symptoms

The major features of Smith-Magenis syndrome include mild to moderate intellectual disability, delayed speech and motor skills, distinctive facial features, sleep disturbances, skeletal and dental abnormalities, and behavioral problems.[1][2]

Facial features in people with SMS may be subtle in early childhood, but usually become more apparent with age. They may include:[1]

  • A broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw
  • A "flattened" appearance to the middle of the face and the bridge of the nose
  • A downward-turned mouth with a full, outward-curving upper lip

While people with SMS often have affectionate, engaging personalities, most also have behavioral problems. These may include:[1]

  • Frequent temper tantrums and outbursts
  • Aggression
  • Anxiety
  • Impulsiveness
  • Difficulty paying attention
  • Self-injury, including biting, hitting, head-banging, and skin picking
  • Repetitive self-hugging (a trait that may be unique to SMS)
  • Compulsively licking the fingers and flipping pages of books (a behavior known as 'lick and flip')

Additional features of SMS may include short stature, scoliosis, reduced sensitivity to pain and temperature, chronic ear infections, obesity, and a hoarse voice.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal tracheobronchial morphology
0005607
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Brachycephaly
Short and broad skull
0000248
Brachydactyly
Short fingers or toes
0001156
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Corticospinal tract hypoplasia
0007016
Deeply set eye
Deep set eye
Sunken eye
Deep-set eyes

[ more ]

0000490
Delayed eruption of primary teeth
Delayed eruption of baby teeth
Delayed eruption of milk teeth
Late eruption of baby teeth
Late eruption of milk teeth

[ more ]

0000680
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech acquisition
Delayed speech
Speech delay
Poor language development
Late-onset speech development
Language development deficit
Language delayed
Language delay
Impaired speech development
Impaired speech and language development
Delayed speech development
Speech and language difficulties
Speech and language delay

[ more ]

0000750
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Frontal bossing
0002007
Global developmental delay
0001263
Hoarse voice
Hoarseness
Husky voice

[ more ]

0001609
Hyporeflexia
Decreased reflexes
Decreased reflex response

[ more ]

0001265
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Large face
Big face
0100729
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Muscular hypotonia
Low or weak muscle tone
0001252
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Obesity
Having too much body fat
0001513
Self-injurious behavior
Self-injurious behaviour
0100716
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Stereotypy
Repetitive movements
Repetitive or self-injurious behavior

[ more ]

0000733
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Taurodontia
0000679
Tented upper lip vermilion
0010804
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Wide nasal bridge
Broad nasal root
Broad nasal bridge
Widened nasal bridge
Increased width of bridge of nose
Increased breadth of nasal bridge
Increased breadth of bridge of nose
Broadened nasal bridge
Wide bridge of nose
Nasal bridge broad
Increased width of nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal form of the vertebral bodies
0003312
Abnormality of cardiovascular system morphology
0030680
Abnormality of the immune system
Immunological abnormality
0002715
Abnormality of the larynx
0001600
Abnormality of the outer ear
Abnormality of the external ear
Ear anomalies
External ear malformations
Outer ear abnormality

[ more ]

0000356
Abnormality of the thyroid gland
Thyroid abnormality
0000820
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Aplasia/Hypoplasia of the corpus callosum
0007370
Broad face
Increased breadth of face
Increased width of face
Wide face

[ more ]

0000283
Broad palm
Broad hand
Broad hands
Wide palm

[ more ]

0001169
Chronic otitis media
Chronic infections of the middle ear
0000389
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Constipation
0002019
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
EEG abnormality
0002353
Everted upper lip vermilion
Outward turned upper lip
0010803
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Feeding difficulties in infancy
0008872
Gait disturbance

Cause

Most people with Smith-Magenis syndrome (SMS) have a deletion of genetic material from a specific region of chromosome 17.[1][3] The deletion is not usually inherited, occurring randomly during the formation of egg or sperm cells in a parent, or in early embryonic development. In rare cases, the deletion may occur to due a parent having a chromosomal balanced translocation.[2] Although the deleted region contains multiple genes, researchers believe that the loss of the RAI1 gene is responsible for most of the features of SMS. The loss of other genes in the deleted region may explain why the features may vary from person to person.[1]

About 10% of people with SMS have a mutation in the RAI1 gene (not a deletion of the larger part of the chromosome).[1][3][2] Although people with an RAI1 mutation have many of the major features of SMS, they are less likely to have short stature, hearing loss, and heart or kidney abnormalities.[1] RAI1 gene mutations may occur randomly, or they may be inherited from a parent in an autosomal dominant manner.[2]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus Genetics contains information on Smith-Magenis syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Smith-Magenis syndrome. Click on the link to view a sample search on this topic.

          References

          1. Smith-Magenis syndrome. Genetics Home Reference (GHR). 2017; https://ghr.nlm.nih.gov/condition/smith-magenis-syndrome.
          2. Smith Magenis Syndrome. NORD. 2017; https://rarediseases.org/rare-diseases/smith-magenis-syndrome/.
          3. Smith ACM, Boyd KE, Elsea SH, et. al. Smith-Magenis Syndrome. GeneReviews. June 28, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1310/.

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