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Angelman syndrome

Reviewed November 2006

What is Angelman syndrome?

Angelman syndrome is a complex genetic disorder that affects the nervous system. Characteristic features of this condition include developmental delay or intellectual disability, severe speech impairment, seizures, small head size (microcephaly), and problems with movement and balance (ataxia). Delayed development can be noted by 6 months to 12 months of age, and other common signs and symptoms usually become apparent in early childhood. People with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling and laughter, a short attention span, and hand-flapping movements. Some affected individuals also have unusually fair skin and light-colored hair.

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?

Angelman syndrome is related to chromosome 15.

Mutations in the UBE3A gene cause Angelman syndrome.

The OCA2 gene is associated with Angelman syndrome.

People normally inherit one copy of the UBE3A gene 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. This parent-specific gene activation is 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 the brain. This loss of gene function likely causes many of the characteristic features of Angelman syndrome.

Several different genetic mechanisms can result in the inactivation or absence of 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 DNA region 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 OCA2 gene is located on the segment of chromosome 15 that is often deleted in Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes. A deletion of the OCA2 gene is associated with light-colored hair and fair skin in some people with this condition.

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

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 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 nearby DNA region that controls gene activation to be passed from one generation to the next.

Where can I find information about treatment for Angelman syndrome?

You may find information on treatment or management of Angelman syndrome or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

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.

  • MedlinePlus - Health information
    • Encyclopedia: Mental Retardation (http://www.nlm.nih.gov/medlineplus/ency/article/001523.htm)
    • Encyclopedia: Speech Disorders (http://www.nlm.nih.gov/medlineplus/ency/article/001430.htm)
    • Health Topic: Developmental Disabilities (http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html)
    • Health Topic: Movement Disorders (http://www.nlm.nih.gov/medlineplus/movementdisorders.html)
  • Additional NIH Resources - National Institutes of Health
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.165)
    • National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/angelman/angelman.htm)
  • Educational resources - Information pages
    • Ask the Geneticist: Angelman syndrome and Prader-Willi syndrome (http://www.askthegen.org/question.php?question_id=20)
    • Ask the Geneticist: Inheritance of Angelman syndrome (http://www.askthegen.org/question.php?question_id=789)
    • California Department of Developmental Services (http://www.ddhealthinfo.org/coursebuilder/?id=1)
    • Children's Hospital Boston (http://www.childrenshospital.org/az/Site2066/mainpageS2066P0.html)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,63/)
    • New York Online Access to Health (NOAH) (http://www.noah-health.org/en/bns/disorders/other/angelman.html)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=72)
    • Penn State Children's Hospital (http://www.hmc.psu.edu/childrens/healthinfo/a/angelman.htm)
    • Swedish Information Center for Rare Diseases (http://www.socialstyrelsen.se/en/rarediseases/Angelman+syndrome.htm)
    • The Wellcome Trust: Imprinting Disorders (http://genome.wellcome.ac.uk/doc_WTD020853.html)
  • Patient support - For patients and families
    • Angelman, Rett, and Prader-Willi Syndromes Consortium (http://rarediseasesnetwork.epi.usf.edu/arpwsc/)
    • Angelman Syndrome Foundation (http://www.angelman.org/)
    • Epilepsy Foundation (http://www.epilepsyfoundation.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Angelman+Syndrome)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/angelman.html)

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

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=angelman)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2240)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22angelman+syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Angelman+Syndrome[MAJR])+AND+(Angelman+syndrome[TIAB])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1080+Days)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Molecular Cytogenetics of Contiguous Gene Syndromes: Mechanisms and Consequences of Gene Dosage Imbalance (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=65)
  • OMIM - Genetic disorder catalog (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=105830)

What other names do people use for Angelman syndrome?

  • AS

See 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?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Angelman syndrome?

ataxia ; cell ; chromosome ; deletion ; developmental delay ; DNA ; gene ; imprinting ; maternal ; microcephaly ; mutation ; nervous system ; pigmentation ; protein ; rearrangement ; reproductive cells ; seizure ; sign ; symptom ; syndrome ; tissue ; translocation ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Barry RJ, Leitner RP, Clarke AR, Einfeld SL. Behavioral aspects of Angelman syndrome: a case control study. Am J Med Genet A. 2005 Jan 1;132(1):8-12. Erratum in: Am J Med Genet A. 2005 Jul 1;136(1):111. Berry, Raymond J [corrected to Barry, Raymond J]. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15578589)
  • Bittel DC, Kibiryeva N, Talebizadeh Z, Driscoll DJ, Butler MG. Microarray analysis of gene/transcript expression in Angelman syndrome: deletion versus UPD. Genomics. 2005 Jan;85(1):85-91. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15607424)
  • Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet. 2000 Summer;97(2):136-46. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11180221)
  • Clayton-Smith J, Laan L. Angelman syndrome: a review of the clinical and genetic aspects. J Med Genet. 2003 Feb;40(2):87-95. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12566516)
  • Gene Review: Angelman Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=angelman)
  • Horsler K, Oliver C. The behavioural phenotype of Angelman syndrome. J Intellect Disabil Res. 2006 Jan;50(Pt 1):33-53. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16316429)
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11748306)
  • 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/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16470747)
  • Williams CA. Neurological aspects of the Angelman syndrome. Brain Dev. 2005 Mar;27(2):88-94. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15668046)

 

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: November 2006
Published: January 23, 2009