Characterization of Angelman Syndrome

Brief Title

Characterization of Angelman Syndrome

Official Title

Angelman Syndrome Natural History Study

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.

Study Type


Primary Outcome

medical morbidity

Secondary Outcome



Angelman Syndrome


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

February 2006

Completion Date

August 2014

Primary Completion Date

August 2014

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

        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




N/A - 60 Years

Accepts Healthy Volunteers



Carlos A. Bacino, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID

RDCRN 5203

Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

Boston Children's Hospital


 Rady Children's Hospital, San Diego

Study Sponsor

Carlos A. Bacino, MD, Principal Investigator, Baylor College of Medicine, Department of Molecular and Human Genetics

Verification Date

February 2021