Protocol Number: 01-HG-0109

Title:

Natural History Study of the Clinical and Molecular Manifestations of Smith-Magenis Syndrome (SMS)

Number:

01-HG-0109

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). 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.

Sponsoring Institute:

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Persons with known or suspected SMS and their parents are eligible for enrollment.

Persons with Smith-Magenis Syndrome confirmed by deletion of 17p.11.2.

Persons with clinical features suggestive of SMS (including midface hypoplasia, prominent forehead, upslanting palpebral fissures, history of infantile hypotonia and /or failure to thrive, early speech/language delay, altered sleep patterns, hoarse deep voice, short stature, brachydactyly, signs of peripheral neuropathy, developmental delay/mental retardation, and/or maladaptive behaviors/autistic like features) in the absence of cytogenetic confirmation of deletion 17p.11.2, and who test negative for other known genetic disorders that overlap with SMS.

Male or female, all ages, all ethnicities.

Parents of persons with known or suspected SMS.

Unaffected sibling or normal twin or sibling to the SMS proband (sibling control).

SMS RESEARCH REGISTRY AND CORE TISSUE BANK INCLUSION CRITERIA:

Individuals (male and female, all ages and all ethnicities) with a confirmed diagnosis of SMS and their parents who voluntarily give informed consent.

EXCLUSION CRITERIA:

Inability to obtain informed consent.

Persons with confirmed cytogenetic diagnosis of trisomy 21, Prader-Willi Syndrome (del 15q), Angelman Syndrome (del 15q), and Velocardiofacial Syndrome (del 22q); molecular confirmation of Fragile X Syndrome or other recognized multiple congenital anomaly/MR syndrome.

Subjects may be excluded from further participation if the diagnosis of SMS is ruled out as a result of the initial screening evaluation.

SMS RESEARCH REGISTRY AND CORE TISSUE BANK EXCLUSION CRITERIA:

Individuals who do not have confirmed diagnosis of SMS.

Special Instructions: Currently Not Provided

Keywords:

Deletion 17p11.2

Contiguous Gene Syndrome

Chromosomal Abnormalities

Phenotype

Genotype

Smith-Magenis Syndrome

Recruitment Keywords:

Smith-Magenis Syndrome

Genetics

Conditions:

Chromosome Abnormalities

Smith Magenis Syndrome

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Chromosome deletion 17p112 (Smith-Magenis syndrome) in seven new patients, four of whom had been referred for fragile-X investigation

Interstitial deletion of (17)(p112p112) in nine patients

Apparent mosaicism for del(17)(p112) ruled out by fluorescence in situ hybridization in a Smith-Magenis syndrome patient

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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Bethesda, Maryland 20892. Last update: 10/15/2004