Angelman syndrome

Información en español Title

Other Names:

AS; Happy puppet syndrome (formerly)

Categories:

Congenital and Genetic Diseases; RDCRN

Summary Summary

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.^[1] Treatment is aimed at addressing each individual's symptoms and may include antiepileptics for seizures; physical, occupational, and speech therapy; and special education services.^[2]

Last updated: 12/31/2015

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Absent speech	Very frequent (present in 80%-99% of cases)
Ataxia	Very frequent (present in 80%-99% of cases)
Behavioral abnormality	Very frequent (present in 80%-99% of cases)
Blue irides	Very frequent (present in 80%-99% of cases)
Brachycephaly	Very frequent (present in 80%-99% of cases)
Broad-based gait	Very frequent (present in 80%-99% of cases)
Cerebral cortical atrophy	Very frequent (present in 80%-99% of cases)
Clumsiness	Very frequent (present in 80%-99% of cases)
EEG abnormality	Very frequent (present in 80%-99% of cases)
Intellectual disability, progressive	Very frequent (present in 80%-99% of cases)
Intellectual disability, severe	Very frequent (present in 80%-99% of cases)
Microcephaly	Very frequent (present in 80%-99% of cases)
Muscular hypotonia	Very frequent (present in 80%-99% of cases)
Seizures	Very frequent (present in 80%-99% of cases)
Hyperreflexia	Frequent (present in 30%-79% of cases)
Hypoplasia of the maxilla	Frequent (present in 30%-79% of cases)
Sporadic	Frequent (present in 30%-79% of cases)
Wide mouth	Frequent (present in 30%-79% of cases)
Widely spaced teeth	Frequent (present in 30%-79% of cases)
Inguinal hernia	Occasional (present in 5%-29% of cases)
Strabismus	Occasional (present in 5%-29% of cases)
Autosomal dominant inheritance	-
Constipation	-
Deeply set eye	-
Drooling	-
Exotropia	-
Fair hair	-
Feeding difficulties in infancy	-
Flat occiput	-
Hyperactivity	-
Hypopigmentation of the skin	-
Limb tremor	-
Motor delay	-
Myopia	-
Nystagmus	-
Obesity	-
Paroxysmal bursts of laughter	-
Progressive gait ataxia	-
Protruding tongue	-
Scoliosis	-
Sleep-wake cycle disturbance	-

Last updated: 9/1/2017

Cause Cause

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.^[1]

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.^[1]

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.^[1]

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.^[1]

Last updated: 3/31/2016

Inheritance Inheritance

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.^[1]

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.^[1]

Last updated: 3/31/2016

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Angelman syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

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

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Angelman syndrome. This website is maintained by the National Library of Medicine.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Angelman syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

How is Anglemans syndrome mistaken for Autism? See answer
We have a 2-year-old son who was diagnosed with Angelman syndrome. He has a deletion of the mother's part on chromosome 15. What are the chances of this syndrome occurring in our next baby? We have another 6-year-old son who is normal. See answer
What is the chance of having another child with Angelman syndrome if a mother has a translocation of chromosomes 15 and 7? Is there additional genetic testing that could be performed? See answer

Have a question? Contact a GARD Information Specialist.

References References

Angelman syndrome. Genetics Home Reference. May 2015; http://ghr.nlm.nih.gov/condition=angelmansyndrome.
Dagli AI, Mueller J, Williams CA. Angelman Syndrome. GeneReviews. May 14, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1144/.

Do you know of a review article? Send us your suggestions.