National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Smith-Magenis syndrome

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]
Last updated: 8/28/2017
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]

Last updated: 8/28/2017

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.

Showing of 104 |
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 eyes
Deep set eye
Sunken eye
[ 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
Delayed language development
Delayed speech acquisition
Delayed speech
Language delay
Impaired speech development
Impaired speech and language development
Delayed speech development
Poor language development
Late-onset speech development
Language development deficit
Language delayed
Speech delay
Speech and language difficulties
Speech and language delay
Deficiency of speech development
[ 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 reflex response
Decreased reflexes
[ 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 bridge
Broadened nasal bridge
Broad nasal root
Increased width of nasal bridge
Increased width of bridge of nose
Increased breadth of nasal bridge
Increased breadth of bridge of nose
Widened nasal bridge
Wide bridge of nose
Nasal bridge broad
[ 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
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hyperacusis 0010780
Hypercholesterolemia
Elevated serum cholesterol
Increased total cholesterol
Elevated total cholesterol
[ more ] 		0003124
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides
[ more ] 		0002155
Impaired pain sensation
Decreased pain sensation
0007328
Malar flattening
Zygomatic flattening
0000272
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent lower jaw
Prominent chin
[ more ] 		0000303
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Morphological abnormality of the middle ear
Middle ear malformation
0008609
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ] 		0000545
Open mouth
Gaped jawed appearance
Gaped mouthed appearance
Slack jawed appearance
[ more ] 		0000194
Pes planus
Flat feet
Flat foot
[ more ] 		0001763
Scoliosis 0002650
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Short palm 0004279
Short philtrum 0000322
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
Velopharyngeal insufficiency
Velopharyngeal incompetence
0000220
Ventriculomegaly 0002119
5%-29% of people have these symptoms
Abnormal localization of kidney
Abnormal localisation of kidneys
0100542
Abnormality of the forearm 0002973
Abnormality of the ureter 0000069
Abnormality of the urinary system
Urinary tract abnormalities
Urinary tract abnormality
Urinary tract anomalies
[ more ] 		0000079
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay
[ more ] 		0000823
Hand polydactyly
Extra finger
0001161
Hypothyroidism
Underactive thyroid
0000821
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Oral cleft
Cleft of the mouth
0000202
Precocious puberty
Early onset of puberty
Early puberty
[ more ] 		0000826
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney
[ more ] 		0008678
Retinal detachment
Detached retina
0000541
Seizure 0001250
1%-4% of people have these symptoms
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality
[ more ] 		0000164
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hyperactivity
More active than typical
0000752
Increased body weight 0004324
Self-mutilation
Deliberate self-harm
Self mutilation
[ more ] 		0000742
Percent of people who have these symptoms is not available through HPO
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect
[ more ] 		0001627
Abnormal renal morphology
Abnormally shaped kidney
Kidney malformation
Kidney structure issue
Structural kidney abnormalities
[ more ] 		0012210
Areflexia
Absent tendon reflexes
0001284
Autosomal dominant inheritance 0000006
Head-banging 0012168
Onychotillomania 0032509
Polyembolokoilamania 0032508
Self hugging 0032521
Sleep-wake inversion 0031849
Sporadic
No previous family history
0003745
Showing of 104 |
Last updated: 7/1/2020
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]
Last updated: 8/28/2017
Most cases of Smith-Magenis syndrome (SMS) are not inherited. SMS usually occurs due to a random genetic change in a parent's sperm or egg cell, or very early in embryonic development. Most people with SMS have no family history of the condition.[1][3]

In a very small number of cases, SMS in a child can result from a parent having a balanced translocation (resulting in a deletion in the child), or from a mutation in the RAI1 gene that was inherited from a parent.[2] Very rarely, parental germline mosaicism has been reported to cause SMS in a child.[2]

Because there are cases in which SMS may be inherited, genetic testing is recommended for parents of children who are diagnosed with SMS. Information from parental testing can help determine if there are risks to other family members.[3]
Last updated: 8/28/2017

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.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Down syndrome, Williams syndrome, brachydactyly-intellectual deficit syndrome (del 2q37), Prader-Willi syndrome, 22q11 deletion syndrome, Sotos syndrome, and 9q34 deletion syndrome (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Smith-Magenis syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Smith-Magenis syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Smith-Magenis syndrome:
    The Smith-Magenis Syndrome Patient Registry (SMSPR)
     

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

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

  • The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

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

  • Genetics Home Reference (GHR) 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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  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/.