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Genetics Home Reference: your guide to understanding genetic conditions
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Angelman syndrome

Reviewed May 2015

What is Angelman syndrome?

Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include delayed development, 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, a short attention span, and a fascination with water are common. Most affected children also have difficulty sleeping and need less sleep than usual.

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 may be described as "coarse." Other common features include unusually fair skin with light-colored hair and 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, Angelman syndrome results when a person 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.

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 cases.

In some people who have Angelman syndrome, the loss of a gene called OCA2 is associated with light-colored hair and fair skin. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.

Related Chromosome(s)

Changes involving this chromosome are associated with Angelman syndrome.

  • chromosome 15

Related Gene(s)

Changes in these genes are associated with Angelman syndrome.

  • OCA2
  • UBE3A

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 diagnosis or management of Angelman syndrome?

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

  • Gene Review: Angelman Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1144)
  • Genetic Testing Registry: Angelman syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0162635)
  • MedlinePlus Encyclopedia: Speech Disorders (http://www.nlm.nih.gov/medlineplus/ency/article/001430.htm)

You might also find information on the diagnosis or management of Angelman syndrome in Educational resources and Patient support.

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Angelman syndrome?

You may find the following resources about Angelman syndrome helpful. These materials are written for the general public.

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

What other names do people use for Angelman syndrome?

  • AS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Angelman syndrome?

Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding Angelman syndrome?

ataxia ; chromosome ; deletion ; disability ; DNA ; embryonic ; epilepsy ; gene ; His ; hyperactivity ; imprinting ; inherit ; inherited ; maternal ; microcephaly ; mutation ; nervous system ; pigmentation ; protein ; rearrangement ; reproductive cells ; scoliosis ; spectrum ; sperm ; syndrome ; translocation ; uniparental disomy

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

References

  • Buiting K. Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):365-76. doi: 10.1002/ajmg.c.30273. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20803659?dopt=Abstract)
  • Gene Review: Angelman Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1144)
  • Gentile JK, Tan WH, Horowitz LT, Bacino CA, Skinner SA, Barbieri-Welge R, Bauer-Carlin A, Beaudet AL, Bichell TJ, Lee HS, Sahoo T, Waisbren SE, Bird LM, Peters SU. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations. J Dev Behav Pediatr. 2010 Sep;31(7):592-601. doi: 10.1097/DBP.0b013e3181ee408e. Erratum in: J Dev Behav Pediatr. 2011 Apr;32(3):267. (http://www.ncbi.nlm.nih.gov/pubmed/20729760?dopt=Abstract)
  • Lalande M, Calciano MA. Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci. 2007 Apr;64(7-8):947-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17347796?dopt=Abstract)
  • Lossie AC, Whitney MM, Amidon D, Dong HJ, Chen P, Theriaque D, Hutson A, Nicholls RD, Zori RT, Williams CA, Driscoll DJ. Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet. 2001 Dec;38(12):834-45. (http://www.ncbi.nlm.nih.gov/pubmed/11748306?dopt=Abstract)
  • Pelc K, Cheron G, Dan B. Behavior and neuropsychiatric manifestations in Angelman syndrome. Neuropsychiatr Dis Treat. 2008 Jun;4(3):577-84. (http://www.ncbi.nlm.nih.gov/pubmed/18830393?dopt=Abstract)
  • Tan WH, Bacino CA, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, Beaudet AL, Bichell TJ, Gentile JK, Glaze DG, Horowitz LT, Kothare SV, Lee HS, Nespeca MP, Peters SU, Sahoo T, Sarco D, Waisbren SE, Bird LM. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan;155A(1):81-90. doi: 10.1002/ajmg.a.33775. (http://www.ncbi.nlm.nih.gov/pubmed/21204213?dopt=Abstract)
  • Van Buggenhout G, Fryns JP. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet. 2009 Nov;17(11):1367-73. doi: 10.1038/ejhg.2009.67. Epub 2009 May 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19455185?dopt=Abstract)
  • Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet A. 2006 Mar 1;140(5):413-8. (http://www.ncbi.nlm.nih.gov/pubmed/16470747?dopt=Abstract)
  • Williams CA. Neurological aspects of the Angelman syndrome. Brain Dev. 2005 Mar;27(2):88-94. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15668046?dopt=Abstract)
  • Williams CA. The behavioral phenotype of the Angelman syndrome. Am J Med Genet C Semin Med Genet. 2010 Nov 15;154C(4):432-7. doi: 10.1002/ajmg.c.30278. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20981772?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2015
Published: September 1, 2015