Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes

OBJECTIVES: I. Investigate phenotype and genotype correlations in patients with Smith-Magenis syndrome (SMS) associated with del(17p11.2).

II. Clinically evaluate SMS patients with unusual deletions or duplication of proximal 17p.

III. Clinically evaluate patients with Williams syndrome with molecular characterization of 7q11.23.

IV. Perform clinical studies of Prader-Willi, Angelman, DiGeorge, and Shprintzen syndrome patients with unique molecular findings in 15q11q13 or 22q11.2.

V. Perform genotype and phenotype correlations in Prader-Willi patients, particularly those with loss of expression of only some of the imprinted transcripts in 15q11-q13.

VI. Evaluate putative Angelman syndrome patients who do not have classic large deletion, uniparental disomy, or imprinting mutations, and perform molecular studies of the Angelman gene, UBE3A, and identify mutations of this gene.

VII. Investigate phenotype and genotype correlations in patients with terminal deletions of chromosome 1p.

Study Overview

• Status: Completed
• Conditions: Prader-Willi Syndrome; DiGeorge Syndrome; Williams Syndrome; Angelman Syndrome; Smith-Magenis Syndrome; Chromosome Abnormalities; Shprintzen Syndrome

Detailed Description

PROTOCOL OUTLINE: Patients undergo clinical, cytogenetic, and molecular studies. These include radiographic, neurologic, developmental, and 24 hour sleep studies, ophthalmologic, otolaryngologic, speech and language, and audiologic exams, echocardiogram, and renal ultrasound.

Smith-Magenis patients are also evaluated with the following: urine melatonin levels during day and night hours; anthropometrics; sleep and behavioral history; and renal, immunologic, and cholesterol studies. A clinical and phenotypic map is constructed.

When appropriate, parental chromosome analysis is performed.

• Study Type: Observational
• Enrollment: 20

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Contiguous gene deletion syndrome, e.g.: Smith-Magenis syndrome Williams syndrome DiGeorge syndrome Shprintzen syndrome (velo-cardio-facial syndrome) Prader-Willi syndrome Angelman syndrome Deletion of chromosome 1p Patient age: Any age

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Collaborators: Baylor College of Medicine
• Investigators: Study Chair: James R. Lupski, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 1999

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: October 1, 2003

More Information

Terms related to this study

• Keywords: Prader-Willi syndrome; neurologic and psychiatric disorders; rare disease; genetic diseases and dysmorphic syndromes; Angelman syndrome; Williams syndrome; DiGeorge syndrome; Shprintzen syndrome; Smith-Magenis syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Parathyroid Diseases; Movement Disorders; Aortic Valve Disease; Heart Valve Diseases; Intellectual Disability; Heart Defects, Congenital; Cardiovascular Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Obesity; Aortic Valve Stenosis; Chronobiology Disorders; 22q11 Deletion Syndrome; Lymphatic Abnormalities; Hypoparathyroidism; Aortic Stenosis, Supravalvular; Syndrome; Prader-Willi Syndrome; Chromosome Disorders; Chromosome Aberrations; Williams Syndrome; Angelman Syndrome; Smith-Magenis Syndrome; DiGeorge Syndrome
• Other Study ID Numbers: 199/11914; BCM-H4299