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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Absent speech	Absent speech development Lack of language development Lack of speech No speech development No speech or language development Nonverbal [ more ]	0001344
Ataxia		0001251
Behavioral abnormality	Behavioral changes Behavioral disorders Behavioral disturbances Behavioral problems Behavioral/psychiatric abnormalities Behavioural/Psychiatric abnormality Psychiatric disorders Psychiatric disturbances [ more ]	0000708
Blue irides	Blue eyes	0000635
Brachycephaly	Short and broad skull	0000248
Broad-based gait	Wide based walk	0002136
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
Clumsiness		0002312
EEG abnormality		0002353
Intellectual disability, progressive	Mental retardation, progressive Progressive mental retardation [ more ]	0006887
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Macroglossia	Abnormally large tongue Increased size of tongue Large tongue [ more ]	0000158
Mandibular prognathia	Big lower jaw Increased projection of lower jaw Increased size of lower jaw Large lower jaw Prominent chin Prominent lower jaw [ more ]	0000303
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Muscular hypotonia	Low or weak muscle tone	0001252
Seizures	Seizure	0001250
30%-79% of people have these symptoms
Hyperreflexia	Increased reflexes	0001347
Hypoplasia of the maxilla	Decreased size of maxilla Decreased size of upper jaw Maxillary deficiency Maxillary retrusion Small maxilla Small upper jaw Small upper jaw bones Upper jaw deficiency Upper jaw retrusion [ more ]	0000327
Sporadic	No previous family history	0003745
Wide mouth	Broad mouth Large mouth [ more ]	0000154
Widely spaced teeth	Wide-spaced teeth Widely-spaced teeth [ more ]	0000687
5%-29% of people have these symptoms
Inguinal hernia		0000023
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Constipation		0002019
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Drooling	Dribbling	0002307
Exotropia	Outward facing eye ball	0000577
Fair hair	Blond hair Fair hair color Flaxen hair color Light colored hair Sandy hair color Straw colored hair Towhead (hair color) [ more ]	0002286
Feeding difficulties in infancy		0008872
Flat occiput		0005469
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
Hyperactivity	More active than typical	0000752
Hypopigmentation of the skin	Patchy lightened skin	0001010
Limb tremor	Involuntary shaking of limb	0200085
Motor delay		0001270
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Obesity	Having too much body fat	0001513
Paroxysmal bursts of laughter		0000749
Progressive gait ataxia		0007240
Protruding tongue	Prominent tongue Tongue sticking out of mouth [ more ]	0010808
Scoliosis	Abnormal curving of the spine	0002650
Sleep-wake cycle disturbance		0006979

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

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

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.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes hypsarrhythmia in West syndrome or the petit mal variant pattern in Lennox-Gastaut syndrome (see these terms). Other differential diagnoses include Rett syndrome, Mowat-Wilson syndrome, X-linked alpha-thalassemia-intellectual deficit syndrome (ATR-X), and 22q13 deletion syndrome (see these terms). Visit the Orphanet disease page for more information.

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 related to 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? We want to hear from you.

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.

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

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.
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.

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/.

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