Smith-Magenis Syndrome (SMS)NCT00013559
Natural History Study of Smith-Magenis Syndrome
An observational study of Smith-Magenis Syndrome (SMS), run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
This study will examine how a rare disease called Smith-Magenis syndrome (SMS) affects people and how they change over time. SMS is caused by a small chromosome 17p11.2 deletion (missing piece). Read more about this study
- Who is it for?
- Ages 1 month to 115 years
- Conditions the study is for
- Smith-Magenis Syndrome (SMS)
- How many people
- 593 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2001to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 115 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients and parents and/or siblings of patients with Smith-Magenis Syndrome (SMS) or suspected SMS.
- INCLUSION CRITERIA FOR LONGITUDINAL SMS NATURAL HISTORY STUDY:
Persons with known or suspected SMS (male/female, all ages, all ethnicities), their parents and/or unaffected siblings are eligible for enrollment. In some cases, a screening evaluation to confirm the diagnosis may occur at NIH and/or via blood samples sent for deletion screening, prior to enrollment. Subjects may be excluded from further participation if the diagnosis of SMS is ruled out after the initial SMS screening evaluation and/or inability to obtain voluntary informed consent.
INCLUSION CRITERIA FOR HOME ASSESSMENT OF SLEEP (HAS) DD/MR-SYNDROME COMPARISON GROUP:
Children (male \& female, all ethnicities) less than18 years with a confirmed diagnosis (based on current accepted diagnostic criteria) of a specified developmental disability (DD)/MR-syndrome reported to include sleep disturbance. These include: Prader-Willi syndrome (PWS), Down syndrome (DS), Cornelia deLange syndrome (CDLS), and/or behavioral diagnosis of autism, ADHD or fragile X syndrome.
EXCLUSION CRITERIA FOR HOME ASSESSMENT OF SLEEP (HAS) DD/MR-SYNDROME COMPARISON GROUP:
Failure to meet established/accepted diagnostic criteria and/or inability to obtain voluntary informed consent (i.e. parental consent for child with developmental delay/MR) is reason for exclusion.
INCLUSION CRITERIA FOR SMS RESEARCH REGISTRY AND CORE TISSUE BANK:
Individuals (male \& female, all ages and all ethnicities) with a confirmed diagnosis of SMS \& their parents who voluntarily give informed consent are eligible for inclusion.
EXCLUSION CRITERIA FOR SMS RESEARCH REGISTRY AND CORE TISSUE BANK:
Individuals who do not have a confirmed diagnosis of SMS.
There is no exclusion based on age, gender, ethnicity or any other factor. Decisionally impaired subjects may be enrolled if the parent, legal guardian, or durable power of attorney (DPA) consents; assent will be obtained when deemed appropriate.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Natural History Study of the Clinical and Molecular Manifestations of Smith-Magenis Syndrome (SMS)
This study will examine how a rare disease called Smith-Magenis syndrome (SMS) affects people and how they change over time. SMS is caused by a small chromosome 17p11.2 deletion (missing piece). The syndrome is associated with distinct physical, developmental and behavioral characteristics, but it is not fully understood. To learn more about this disease, a multidisciplinary research team will study:
- The range and type of medical, behavioral, and learning problems of people with SMS
- The deletion of chromosome 17p11.2 to find the gene or genes that cause SMS
- Whether certain specific genetic changes cause certain specific medical problems
- What signs and symptoms must be present to make a diagnosis of SMS
- The impact that a child with SMS has on his or her family members.
Read more
Patients of all ages with SMS may be eligible for this study. They will be evaluated by a team of medical specialists at the NIH Clinical Center over the course of several days. Parents of patients will be asked to provide copies of past medical records and tests results for review. They will provide a family medical history and information on the child s prenatal, developmental, behavioral and medical histories.
The study may involve the following evaluations: physical, neurological and psychological exams; ear, nose and throat evaluation; speech, language and swallowing evaluation; hearing test; eye examination; imaging studies (e.g., X-rays, ultrasound, MRI); developmental and behavioral assessment; rehabilitation evaluation with gait (walking) analysis; urinalysis, blood, and/or skin cell studies; sleep study; other consultations as required. A tissue sample (blood or cheek swab or skin biopsy) may be taken for genetic studies. To obtain a cheek swab, a small brush is rubbed against the inside of the cheek to wipe off some cells. For a skin biopsy, a small area of skin is numbed with a local anesthetic and a small circle of skin, usually about 1/8 inch, is removed with a biopsy tool. Parents may be asked to complete questionnaires about their child s growth and development, therapies, medications, sleep, development and behavioral concerns. They also may be asked to bring their child to NIH for follow-up visits every 6 months to 3 years, depending on the child s age. The purpose of these visits is to see how the child changes over time and to conduct additional tests.
Parents may also be asked to enroll their child in a SMS Research Registry and provide tissue samples for a SMS Research Core Tissue Bank. The research registry is a confidential database of individuals diagnosed with SMS. Its purpose is to facilitate SMS research initiatives and promote the development of improved treatments for SMS. Enrollment requires completing a 30-minute questionnaire. The tissue bank stores tissue cultures and cell lines created for future SMS research. About 2 teaspoons of blood are drawn from adult patients and 1 to 3 teaspoons from children, depending on their size. Tissue samples can be obtained by skin biopsy or during a scheduled surgical procedure.
Read the detailed description
This project investigates the clinical manifestations and molecular genetic defects of Smith-Magenis Syndrome (SMS), a rare (1/15,000 1/25,000) clinically recognizable yet often under diagnosed multiple congenital anomaly/intellectual disability (MCA/ID) syndrome (OMIM #182290). The syndrome is characterized by a distinct pattern of minor craniofacial and skeletal anomalies, expressive speech/language delays, psychomotor and growth retardation, and a striking neurobehavioral phenotype that includes a circadian sleep disorder. The majority of cases (~90%) are due to de novo interstitial deletion of chromosome 17p11.2 that includes the RAI1 (retinoic acid induced 1) gene; however, heterozygous RAI1 mutations account for about 10% of cases. While clinical variability exists, haploinsufficiency of RAI1 (by deletion or mutation) is believed to be responsible for most of the common features that characterize the syndrome.
Individuals with confirmed or clinically suspected SMS, their parents, and/or unaffected siblings will be enrolled in this comprehensive longitudinal natural history study. An NIH interdisciplinary SMS Research Team (SMS-RT) of clinical and basic science researchers, in collaboration with extramural investigators, will conduct comprehensive clinical and molecular analyses to delineate the physiological, developmental (cognitive), behavioral, biochemical, and cellular processes that characterize the syndrome. The protocol aims to: characterize the phenotypic variability, natural history and underlying pathophysiology of SMS; delineate the neurobehavioral phenotype with respect to sleep disturbance, cognition, mood and maladaptive behaviors and sensory processing dysfunction; investigate the physiologic and functional aspects specifically underlying delays in speech/language and motor development; explore genotype/phenotype correlations to identify gene(s) or modifiers that contribute to phenotypic variability; determine potential intervention and therapeutic strategies likely to improve outcome; and evaluate the psychosocial impact of SMS on the family system. Offsite enrollment of two pediatric comparison groups to participate in the Home Assessment of Sleep (HAS) are also enrolled: 1) unaffected siblings/control group; and 2) a DD/ID-comparison group of children with developmental/intellectual disabilities associated with sleep disturbances.
- Conditions
- Smith-Magenis Syndrome (SMS)
- Keywords
- Sleep Disturbance, Developmental Delay/Intellectual Disability, Deletion 17p11.2, Chromosomal Abnormalities, Behavioral Phenotype, Natural History, Smith-Magenis Syndrome, Genetics
- Medical subject headings
- Smith-Magenis Syndrome, Parasomnias, Learning Disabilities, Intellectual Disability, Chromosome Aberrations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Family | Parents and/or siblings of patients with Smith-Magenis Syndrome (SMS) or suspected SMS. | |
| Patients | Patients with Smith-Magenis Syndrome (SMS) or suspected SMS. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural History
The major objective of this project is to investigate the clinical and molecular manifestations, phenotypic variability, natural history and pathogenesis of Smith-Magenis syndrome (SMS).
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2001 (estimated)
- Study start19 Mar 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Smith-Magenis Syndrome (SMS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 593 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- William A Gahl, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00013559
- Sponsor's protocol ID
- 010109
- Other IDs
- 01-HG-0109
- Status last verified
- 4 Sep 2026
- First submitted
- 20 Mar 2001
- Last updated
- 9 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lee NR, Niu X, Zhang F, Clasen LS, Kozel BA, Smith ACM, Wallace GL, Raznahan A. Variegation of autism related traits across seven neurogenetic disorders. Transl Psychiatry. 2022 Apr 7;12(1):149. doi: 10.1038/s41398-022-01895-0.
PubMed 35393403
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of the Clinical and Molecular Manifestations of Smith-Magenis Syndrome (SMS)
- ClinicalTrials.gov ID
- NCT00013559
- Acronym / sponsor ID
- 010109
- Conditions
- Smith-Magenis Syndrome (SMS)
- Keywords
- Sleep Disturbance, Developmental Delay/Intellectual Disability, Deletion 17p11.2, Chromosomal Abnormalities, Behavioral Phenotype, Natural History, Smith-Magenis Syndrome, Genetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 593 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 19 Mar 2001 (actual)
- First posted
- 21 Mar 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine how a rare disease called Smith-Magenis syndrome (SMS) affects people and how they change over time. SMS is caused by a small chromosome 17p11.2 deletion (missing piece). The syndrome is associated with distinct physical, developmental and behavioral characteristics, but it is not fully understood. To learn more about this disease, a multidisciplinary research team will study:
- The range and type of medical, behavioral, and learning problems of people with SMS
- The deletion of chromosome 17p11.2 to find the gene or genes that cause SMS
- Whether certain specific genetic changes cause certain specific medical problems
- What signs and symptoms must be present to make a diagnosis of SMS
- The impact that a child with SMS has on his or her family members.
Patients of all ages with SMS may be eligible for this study. They will be evaluated by a team of medical specialists at the NIH Clinical Center over the course of several days. Parents of patients will be asked to provide copies of past medical records and tests results for review. They will provide a family medical history and information on the child s prenatal, developmental, behavioral and medical histories.
The study may involve the following evaluations: physical, neurological and psychological exams; ear, nose and throat evaluation; speech, language and swallowing evaluation; hearing test; eye examination; imaging studies (e.g., X-rays, ultrasound, MRI); developmental and behavioral assessment; rehabilitation evaluation with gait (walking) analysis; urinalysis, blood, and/or skin cell studies; sleep study; other consultations as required. A tissue sample (blood or cheek swab or skin biopsy) may be taken for genetic studies. To obtain a cheek swab, a small brush is rubbed against the inside of the cheek to wipe off some cells. For a skin biopsy, a small area of skin is numbed with a local anesthetic and a small circle of skin, usually about 1/8 inch, is removed with a biopsy tool. Parents may be asked to complete questionnaires about their child s growth and development, therapies, medications, sleep, development and behavioral concerns. They also may be asked to bring their child to NIH for follow-up visits every 6 months to 3 years, depending on the child s age. The purpose of these visits is to see how the child changes over time and to conduct additional tests.
Parents may also be asked to enroll their child in a SMS Research Registry and provide tissue samples for a SMS Research Core Tissue Bank. The research registry is a confidential database of individuals diagnosed with SMS. Its purpose is to facilitate SMS research initiatives and promote the development of improved treatments for SMS. Enrollment requires completing a 30-minute questionnaire. The tissue bank stores tissue cultures and cell lines created for future SMS research. About 2 teaspoons of blood are drawn from adult patients and 1 to 3 teaspoons from children, depending on their size. Tissue samples can be obtained by skin biopsy or during a scheduled surgical procedure.
Detailed description
This project investigates the clinical manifestations and molecular genetic defects of Smith-Magenis Syndrome (SMS), a rare (1/15,000 1/25,000) clinically recognizable yet often under diagnosed multiple congenital anomaly/intellectual disability (MCA/ID) syndrome (OMIM #182290). The syndrome is characterized by a distinct pattern of minor craniofacial and skeletal anomalies, expressive speech/language delays, psychomotor and growth retardation, and a striking neurobehavioral phenotype that includes a circadian sleep disorder. The majority of cases (~90%) are due to de novo interstitial deletion of chromosome 17p11.2 that includes the RAI1 (retinoic acid induced 1) gene; however, heterozygous RAI1 mutations account for about 10% of cases. While clinical variability exists, haploinsufficiency of RAI1 (by deletion or mutation) is believed to be responsible for most of the common features that characterize the syndrome.
Individuals with confirmed or clinically suspected SMS, their parents, and/or unaffected siblings will be enrolled in this comprehensive longitudinal natural history study. An NIH interdisciplinary SMS Research Team (SMS-RT) of clinical and basic science researchers, in collaboration with extramural investigators, will conduct comprehensive clinical and molecular analyses to delineate the physiological, developmental (cognitive), behavioral, biochemical, and cellular processes that characterize the syndrome. The protocol aims to: characterize the phenotypic variability, natural history and underlying pathophysiology of SMS; delineate the neurobehavioral phenotype with respect to sleep disturbance, cognition, mood and maladaptive behaviors and sensory processing dysfunction; investigate the physiologic and functional aspects specifically underlying delays in speech/language and motor development; explore genotype/phenotype correlations to identify gene(s) or modifiers that contribute to phenotypic variability; determine potential intervention and therapeutic strategies likely to improve outcome; and evaluate the psychosocial impact of SMS on the family system. Offsite enrollment of two pediatric comparison groups to participate in the Home Assessment of Sleep (HAS) are also enrolled: 1) unaffected siblings/control group; and 2) a DD/ID-comparison group of children with developmental/intellectual disabilities associated with sleep disturbances.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Family | – | –Parents and/or siblings of patients with Smith-Magenis Syndrome (SMS) or suspected SMS. |
| Patients | – | –Patients with Smith-Magenis Syndrome (SMS) or suspected SMS. |
Who may qualify
- Ages
- 1 month to 115 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients and parents and/or siblings of patients with Smith-Magenis Syndrome (SMS) or suspected SMS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Natural History
Time frame: Ongoing
The major objective of this project is to investigate the clinical and molecular manifestations, phenotypic variability, natural history and pathogenesis of Smith-Magenis syndrome (SMS).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Derived from this study: PubMed 35393403Lee NR, Niu X, Zhang F, Clasen LS, Kozel BA, Smith ACM, Wallace GL, Raznahan A. Variegation of autism related traits across seven neurogenetic disorders. Transl Psychiatry. 2022 Apr 7;12(1):149. doi: 10.1038/s41398-022-01895-0.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Smith-Magenis Syndrome (SMS)
Recruiting
Smith Magenis Syndrome and Autism Spectrum Disorders
Smith-Magenis Syndrome, Autism Spectrum Disorder
Enrolling by invitation
Parent and Infant Inter(X)Action Intervention (PIXI)
Fragile X Syndrome, Angelman Syndrome
RecruitingObservational study
Clinical and Molecular Biomarker Studies in RAI1 (Retinoic Acid-Induced 1) -Related Disorders
RAI1 Gene 17P11.2 Deletion+Duplication
RecruitingObservational study
Development of Clinical Database of Individuals With Smith-Magenis Syndrome and Sleep Disturbances
Sleep Disturbances in Smith-Magenis Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William A Gahl, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Smith-Magenis Syndrome (SMS), run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Natural History (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00013559, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.