Characterization of Angelman Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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Angelman Syndrome Natural History Study

Conditions
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Angelman Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecular diagnosis of Angelman syndrome OR 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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| medical morbidity | to characterize the medical problems associated with Angelman syndrome, and to determine the relative prevalence of those problems in the different molecular subclasses of Angelman syndrome | annually | 
| developmental progress | Assess with a variety of neuropsychological instruments, including Bayley Scales of Infant Development, Vineland Adaptive Behavior Scales, Preschool Language Scale | annually | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| autism | Evaluate for autism spectrum disorder using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised | annually | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Developmental Disorders