Clinical Trial: Natural History Study of Smith-Magenis Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

Brief 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

Detailed Summary:

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 mo
Sponsor: National Human Genome Research Institute (NHGRI)

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: March 20, 2001
Date Started: March 13, 2001
Date Completion:
Last Updated: May 9, 2017
Last Verified: May 2, 2017