Characterization of Angelman Syndrome

Angelman Syndrome Clinical Trial

Official title:

Angelman Syndrome Natural History Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00296764
• Other study ID #: RDCRN 5203
• Secondary ID: U54RR019478
• Status: Completed
• Start date: February 2006
• Est. completion date: August 2014

Study information

• Verified date: February 2021
• Source: Boston Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Angelman Syndrome
• Syndrome

Locations

Country	Name	City	State
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	Baylor College of Medicine	Houston	Texas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rady Children's Hospital San Diego	San Diego	California

Sponsors (7)

Lead Sponsor	Collaborator
Boston Children's Hospital	Baylor College of Medicine, Children's Hospital Medical Center, Cincinnati, Greenwood Genetic Center, National Center for Research Resources (NCRR), Rady Children's Hospital, San Diego, Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (5)

Locke DP, Segraves R, Nicholls RD, Schwartz S, Pinkel D, Albertson DG, Eichler EE. BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. J Med Genet. 2004 Mar;41(3):175-82. — View Citation

Peters SU, Beaudet AL, Madduri N, Bacino CA. Autism in Angelman syndrome: implications for autism research. Clin Genet. 2004 Dec;66(6):530-6. — View Citation

Smith JC. Angelman syndrome: evolution of the phenotype in adolescents and adults. Dev Med Child Neurol. 2001 Jul;43(7):476-80. — View Citation

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. — View Citation

Williams CA, Lossie A, Driscoll D; R.C. Phillips Unit. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001 Jun 1;101(1):59-64. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	developmental progress	Assess with a variety of neuropsychological instruments, including Bayley Scales of Infant Development, Vineland Adaptive Behavior Scales, Preschool Language Scale	annually
Secondary	autism	Evaluate for autism spectrum disorder using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised	annually