> Angelman Syndrome

• Alternative Names
• Symptoms & Characteristics
• Treatment
• How Common Is It?
• Genetics & Inheritance
• Genetic Testing
• Support & More Information

Alternative Names

AS

Symptoms & Characteristics

Angelman syndrome (AS) is a genetic condition that affects the nervous system. Characteristic features of this condition include:

• Developmental delay or mental retardation

• Severe speech impairment

• Seizures

• Small head size (microcephaly)

• Problems with movement and balance (ataxia)

• Happy, excitable behavior

• Hand-flapping movements

• Short attention span

• Fair skin and hair (in some people)

Treatment

There is no cure for Angelman syndrome. Early diagnosis, routine surveillance and treatment may help to manage some of the symptoms and sometimes prevent related problems.

How Common Is It?

About 1 in 12,000 to 1 in 20, 000 people are affected with Angelman syndrome.

• There is debate, but some studies have shown that there may be an increased incidence in pregnancies that were conceived using assisted reproductive technologies (ART), like intracytoplasmic sperm injection (ICSI).

Genetics & Inheritance

Angelman syndrome is caused by the loss of the maternally contributed UEB3A gene on chromosome 15 at the location q11-q13. This chromosome region also contains other genes that do not appear to cause AS.

People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on in many of the body's tissues. However, in the brain, only the copy inherited from mom (the maternal copy) is turned on. This parent-specific gene activation is called genomic imprinting. If the maternal copy of the UBE3A gene is lost, a person will have no active copies of the gene in the brain and will have the symptoms of Angelman syndrome.

Loss of the maternal copy of UBE3A can occur by one of several mechanisms. These mechanisms can include:

• A mutation in UBE3A gene (10% of cases).

• Deletion of 15q11-q13 (70% of cases).

• Chromosome abnormality that interrupts the proper functioning of the gene, including an inversion or chromosome translocation (1% of cases or less).

• Paternal uniparental disomy (UPD), which means that two normal copies of chromosome 15 or the 15q11-q13 region are present, but they are both inherited from the same parent, dad (7% of cases).

• Imprinting errors caused by DNA methylation abnormalities lead to an inactive maternal copy (3% of cases).

In about 10% of cases, a genetic cause is yet to be found. As such, there may be mutations in other genes that also cause AS.

An additional deletion of the OCA2 gene in this same chromosome region is associated with the light-colored hair and fair skin in some people with AS.

Most affected people do not have a family history and are the first one in their family to be affected. The recurrence risk for AS varies and depends on the specific mechanism by which the maternal copy of UBE3A is lost.

There are other genetic conditions, like Rett syndrome, that have characteristics that overlap with Angelman syndrome. A genetic consultation with a trained genetic professional is important for a complete evaluation, accurate diagnosis, as well as discussion of the benefits and limitations of testing and recurrence risk.

Genetic Testing

Clinical genetic testing for Angelman syndrome may be available through an in person genetic consultation for people who are considered at risk. Use our find a genetic professional directory to locate a trained genetic professional in your area.

• A medical geneticist can also be found through the American College of Medical Genetics website.

• A genetic counselor can also be found through the National Society of Genetic Counselors website.

Support & More Information

More information can be found at:

• Genetics Home Reference

Support can be found at:

• Angelman Syndrome Foundation