Disease Directory Smith-Magenis Syndrome
Neurological

Smith-Magenis Syndrome

Also known as: SMS, RAI1 haploinsufficiency, 17p11.2 deletion syndrome

Prevalence

1-9 per 100,000 (Orphanet)

Onset

Infantile, Childhood

Type

Genetic (chromosomal deletion or RAI1 point mutation, usually de novo)

Gene

RAI1

About Smith-Magenis Syndrome

Smith-Magenis syndrome is caused by haploinsufficiency of the RAI1 gene due to interstitial deletion of chromosome 17p11.2 or point mutation in RAI1. Characteristic features include a distinctive behavioral phenotype with self-injurious behavior, self-hugging stereotypy, inverted circadian rhythm (daytime melatonin secretion causing sleep disturbance), and intellectual disability. Facial features become more pronounced with age, and patients often have hearing loss, short stature, and brachydactyly.

Common Clinical Features

Inverted sleep-wake cycle Self-injurious behavior Intellectual disability Distinctive facial features Hearing loss Short stature Brachydactyly

Clinical Trial Eligibility Tips

What to know before applying to Smith-Magenis Syndrome trials.

Chromosome 17p11.2 deletion size or specific RAI1 mutation type must be documented — deletion versus point mutation may affect trial eligibility

Actigraphy documenting inverted circadian rhythm (daytime sleep) and polysomnography are key baseline measures

Melatonin-targeted sleep trials require baseline sleep diary and actigraphy for at least 4 weeks before enrollment

Behavioral phenotype assessment (ABC-C, Vineland) and adaptive behavior scores are required eligibility measures

Patient Resources

Patient Organization

PRISMS (Parents and Researchers Interested in Smith-Magenis Syndrome)

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Natural History Registry

SMS Research Foundation Registry

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Orphanet

European reference resource for rare diseases (ORPHA:819)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Smith-Magenis Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Smith-Magenis Syndrome. Updated daily.

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