Characterization of Angelman Syndrome

NCT ID: NCT00296764

Last Updated: 2021-03-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 302 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2014-08-31

Brief Summary

Angelman Syndrome (AS) is a developmental disorder that is caused by a deficiency of a maternally transmitted gene. It is inherited at birth, and affects movement, speech, and social demeanor. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over an extended period of time.

Detailed Description

AS is a developmental disorder that affects movement, speech, and social demeanor. The disorder is caused by a deficiency of a maternally transmitted gene and is inherited at birth. Children with AS, however, are often not diagnosed until they are between 3 and 7 years old. Symptoms of AS may include, but are not limited to, functionally severe developmental delay; speech impairments; movement or balance problems; and behavioral uniqueness, including any combination of frequent laughter or smiling, apparent happy demeanor, easily excitable personality, hand flapping movements, and short attention span. There are four molecular variations of AS, but past clinical studies have been inconsistent in highlighting the phenotypic differences between them. This study will gain a better understanding of the disease progression and clinical features of AS by observing children with AS over a period of 5 to 10 years. The study will also attempt to establish genotype-phenotype correlations, which might aid in future clinical care of AS patients.

Participation in this observational study will be limited to current or future patients at one of the five study sites. A clinical evaluation will be performed at baseline, including a general patient history, physical and neurological examinations, a nutritional assessment, neuro-imaging, electroencephalography, laboratory testing, and neurodevelopmental testing. A blood sample or mucosal sample will also be taken at baseline to acquire DNA for potential genetic testing. All assessments except the neuro-imaging, electroencephalography, and blood sampling will be repeated at yearly study visits for as long as funding can be secured. In addition, participants will be photographed and perhaps videotaped on a yearly basis in order to document clinical phenotypes and any neurologic abnormalities. Participants may be followed-up for a total of 10 years.

Conditions

Angelman Syndrome

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. Molecular diagnosis of Angelman syndrome OR

2. Meets all major diagnostic criteria for Angelman Syndrome and 3 of the 6 minor criteria:

Major Criteria:

• Functionally severe developmental delay
• Speech impairment; none or minimal words used
• Movement or balance disorder
• Behavioral uniqueness, frequent laughs/smiling, excitable personality, hand flapping, short attention span

Minor Criteria:

• Deceleration in head circumference growth (post-natal)
• Seizures (myoclonic, absence, drop, tonic-clonic)
• Abnormal EEG (with patterns suggestive of AS, or hypsarrhythmia)
• Sleep disturbance
• Attraction to or fascination with water
• Drooling

Exclusion Criteria

• Does not meet diagnostic criteria for Angelman Syndrome
• Other medical or genetic disorders (except autism)
• Born extremely premature

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rady Children's Hospital, San Diego

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Greenwood Genetic Center

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wen-Hann Tan

Site PI (Lead PI: Lynne M. Bird, MD - Univ. of California, San Diego)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlos A. Bacino, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine, Department of Molecular and Human Genetics

Lynne Bird, MD

Role: STUDY_CHAIR

Rady Childrens Hospital San Diego, UCSD Dept of Pediatrics

Steven A. Skinner, MD

Role: PRINCIPAL_INVESTIGATOR

Greenwood Genetic Center

Wen-Hann Tan, BMBS

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Logan K Wink, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Sarika Peters, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Rady Children's Hospital San Diego

San Diego, California, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Cincinnati Children's Hospital and Medical Center

Cincinnati, Ohio, United States

Greenwood Genetic Center

Greenwood, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Varela MC, Kok F, Otto PA, Koiffmann CP. Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects. Eur J Hum Genet. 2004 Dec;12(12):987-92. doi: 10.1038/sj.ejhg.5201264.

Reference Type: BACKGROUND

PMID: 15470370 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 15521981 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: DERIVED

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Reference Type: DERIVED

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Reference Type: DERIVED

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Reference Type: DERIVED

PMID: 25283752 (View on PubMed)

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Reference Type: DERIVED

PMID: 25071871 (View on PubMed)

Other Identifiers

U54RR019478

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RDCRN 5203

Identifier Type: -

Identifier Source: org_study_id