Angelman syndrome

Angelman syndrome is a complex genetic disorder that affects the brain and nervous system. Characteristic features of the condition include developmental delay or mental retardation, severe speech impairment, and problems with movement and balance (ataxia). People with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, excessive laughter, and hand-flapping movements. Some affected individuals also have unusually fair skin and light-colored hair.

Angelman syndrome affects an estimated 1 in 10,000 to 20,000 people.

Angelman syndrome is a chromosomal condition related to chromosome 15.

Mutations in the UBE3A gene cause Angelman syndrome.

The OCA2 gene is associated with Angelman syndrome.

People normally have two copies of the UBE3A gene, one from each parent. Both copies of this gene are active in many of the body's tissues. In the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. If the maternal copy is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the UBE3A gene in the brain. This loss of gene function likely causes many of the characteristic features of Angelman syndrome.

The UBE3A gene is located on chromosome 15. Most cases of Angelman syndrome (about 70 percent) occur when a segment of maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.

The OCA2 gene is located on the segment of chromosome 15 that is often deleted in Angelman syndrome. A loss of this gene results in unusually light-colored hair and fair skin in some people with the condition.

In a small percentage of cases, a person with Angelman syndrome has two copies of chromosome 15 inherited from his or her father (paternal copies) instead of one copy from each parent. This phenomenon is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the center that controls activation of the UBE3A gene. Both of these genetic changes can abnormally inactivate UBE3A or other genes on the maternal copy of chromosome 15.

The causes of Angelman syndrome are unknown in 10 to 15 percent of cases.

Most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in maternal chromosome 15 or by paternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells or in early fetal development. Affected people typically have no history of the disorder in their family.

Rarely, a genetic change responsible for Angelman syndrome can be inherited. For example, it is possible for a mutation in the UBE3A gene or in the center that controls gene activation in this region to be passed from one generation to the next.

You may find the following resources about Angelman syndrome helpful.

• NIH Publications - National Institutes of Health
  National Institute of Neurological Disorders and Stroke
• MedlinePlus - Health Information
  Health Topic: Movement Disorders
• Genes and Disease - Genetic disorder summaries
• Educational resources - Information pages (3 links)
• Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What is a chromosome?
• Can changes in chromosomes cause disorders?
• Are chromosomal disorders inherited?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

ataxia ; chromosome ; deletion ; developmental delay ; gene ; imprinting ; maternal ; mental retardation ; mutation ; nervous system ; rearrangement ; translocation ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.