Contact Us

Angelman's Syndrome on Genetics Home Reference

< Back to Previous Page

Angelman, From Genetics Home Reference

By: Genetics Home Reference, National Institutes of Health

Article in the Public Domain from Genetics Home Reference on the NIH Website as originally published on their website

What is Angelman Syndrome?

Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include developmental delay, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy) and a small head size (microcephaly). Delayed development becomes noticeable by the age of 6 to 12 months, and other common signs and symptoms usually appear in early childhood. Children with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Hyperactivity and a short attention span are common. Most affected children also have difficulty sleeping and need less sleep than usual. Some affected individuals have unusually fair skin and light-colored hair. With age, people with Angelman syndrome become less excitable, and the sleeping problems tend to improve. However, affected individuals continue to have intellectual disability, severe speech impairment, and seizures throughout their lives. Adults with Angelman syndrome have distinctive facial features that are described as "coarse." Some also develop an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal.

How common is Angelman syndrome?

Angelman syndrome affects an estimated 1 in 12,000 to 20,000 people.

What are the genetic changes related to Angelman syndrome?

Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation is caused by a phenomenon called genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.

Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the 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. In a small percentage of cases, a person with Angelman syndrome inherits two copies of chromosome 15 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 region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.

A deletion of a gene called OCA2 is associated with light-colored hair and fair skin in some people with Angelman syndrome. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.

The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the disorder in these individuals.

Read more about the OCA2 and UBE3A genes and chromosome 15.

Can Angelman syndrome be inherited?

Most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic 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 nearby region of DNA that controls gene activation to be passed from one generation to the next.

Where can I find information about treatment for Angelman syndrome?

These resources address the management of Angelman syndrome and may include treatment providers.

* Gene Review: Angelman Syndrome

You might also find information on treatment of Angelman syndrome in Educational resources and Patient support.



Featured Organization: Genetics Home Reference, part of the National Institutes of Health

Our thanks to Genetics Home Reference for providing this valuable information.

The mission of Genetics Home Reference is to provide consumer-friendly information about the effects of genetic variations on human health.

Please support our contributing Organizations and visit Genetics Home Reference

Tags: Angelman Syndrome SLP Article