Angelman syndrome

What causes Angelman syndrome?

Angelman syndrome is caused by a loss of function of a gene called UBE3A on chromosome 15. The exact mechanism that causes this loss of function is complex. 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 is active. This parent-specific gene activation is known as 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 occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases, 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, instead of one copy from each parent. This 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.

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

Last updated on 05-01-20

How might 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. In these instances, 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.

Last updated on 05-01-20

After having one child with Angelman syndrome, what is the chance that future children will inherit it as well?

Although most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15, the risk of having another child with Angelman syndrome depends on the specific cause. You will need to speak with a genetics professional to understand the risk in future pregnancies that are specific to your situation.

Last updated on 05-01-20

What is Angelman syndrome?

Angelman syndrome is a genetic disorder that primarily affects the nervous system. Characteristic features of this condition include developmental delay, intellectual disability, severe speech impairment, problems with movement and balance (ataxia), epilepsy, and a small head size. Individuals with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. Most cases of Angelman syndrome are not inherited, although in rare cases a genetic change responsible for Angelman syndrome can be inherited from a parent. Treatment is aimed at addressing each individual's symptoms and may include antiepileptics for seizures; physical, occupational, and speech therapy; and special education services.

Last updated on 05-01-20

Is there any way to avoid having a child with Angelman syndrome in a future pregnancy?

There are a number of genetic tests that can be used to inform a couple about the possible outcomes of a current or future pregnancy. Examples of two such tests are prenatal diagnosis and preimplantation genetic diagnosis (PGD).

Prenatal diagnosis can be used to diagnose a condition in a developing fetus. If the underlying genetic cause of a disorder in a family is known, testing can be completed to analyze the genetic material of the fetus. This is typically completed around 10-13 weeks' gestation via chorionic villus sampling or around 15+ weeks' gestation via amniocentesis. Prenatal diagnosis may help parents prepare emotionally for the birth and to plan the delivery with their health care providers. Parents can also use this information to make decisions regarding whether or not to continue the pregnancy.

PGD is an alternative to prenatal diagnosis. It is used following in vitro fertilization to diagnose a genetic disease or condition in embryos. Only embryos that do not carry the disease-causing mutation are implanted in the mother's womb. PGD allows testing to occur before a pregnancy begins. In many cases, the disease- causing mutation must be identified in an affected parent before PGD or prenatal diagnosis can be performed.

Last updated on 05-01-20

What is the chance of having another child with Angelman syndrome if a mother has a translocation involving chromosome 15?

In about 1 percent of cases, Angelman syndrome is caused by an inherited abnormality in chromosome 15. In these cases, the chance of having another child with Angelman syndrome depends on the specific chromosome abnormality, and could be as high as 50 percent. A genetics professional can provide information on an individual's risk of having another child with Angelman syndrome.

Last updated on 05-01-20

How is Angleman syndrome mistaken for Autism?

Signs and symptoms of Angelman syndrome can overlap with those of autism. Certain behaviors, hand‑flapping, and language problems can be similar to those seen in autism spectrum disorders. This has led to some children with Angelman syndrome being misdiagnosed as having autism. To further complicate things, studies have shown that a small portion of children with Angelman syndrome do in fact also have autism.

If you are interested in learning more on this topic, the following article published by the Angelman Syndrome Foundation offers further details. The discussion of Autism and Angelman syndrome begins on page 17.
http://www.angelman.org/_angelman2/assets/File/facts%20about%20as%202009%203-19-10.pdf

Last updated on 05-01-20

Name: Angelman Syndrome Foundation 75 Executive Drive, Suite 327
Aurora, IL, 60504, United States
Phone: 630-978-4245 Toll Free: 1-800-432-6435 Fax : 630-978-7408 Email: http://www.angelman.org/contact-us/ Url: http://www.angelman.org/
Name: Foundation for Angelman Syndrome Therapeutics PO Box 608
Downers Grove, IL, 60515-0608, United States
Phone: 630-852-FAST (3278) Toll Free: 866-783-0078 Fax : 630-852-3270 Email: http://www.cureangelman.org/contact.aspx Url: http://www.cureangelman.org/

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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