Authors: Douglas Nordli, MD, Mayo Clinic Florida/Nemours Jacksonville

Alison L. Christy, MD, PhD, Providence Pediatric Neurology at St. Vincent Medical Center—Portland, Oregon

Reviewed: April 2022

SUMMARY

Angelman syndrome (AS) is a genetic syndrome. It is characterized by:

• Severe learning difficulties 
• A small head size (microcephaly) 
• Poor balance and coordination 
• Distinct facial features 
• Seizures 
• A happy personality

A genetic variation involving chromosome 15 causes these symptoms.

The first sign of AS is often delayed development in early childhood. Young children may have delays in:

• Sitting 
• Pointing to objects 
• Standing 
• Walking 
• Language 

Many children with AS have trouble with feeding. It may be hard for them to gain weight as young children. 

As they grow older, they often have significant trouble with sleep. Many children with AS require much less sleep than others. The majority of children born with AS have seizures. 

There is no cure for AS. Treatment is focused on:

• Controlling seizures 
• Managing overall health 
• Improving sleep 

Children with AS can live a normal lifespan. However, controlling seizures may be important to survival.

Children with AS usually have severe intellectual disability. For this reason, they require lifelong care.

Disorder Overview

SIGNS AND SYMPTOMS

Angelman syndrome usually includes these characteristics:

DIAGNOSIS

A pediatric neurologist can usually diagnose AS with an evaluation. Three factors helpful for a diagnosis include:

• A medical history 
• A physical exam 
• A review of videos of the child 

LABORATORY INVESTIGATIONS

Certain kinds of tests can be helpful in AS. These tests include:

• Electroencephalography (EEG). EEG can detect seizures. Not all patients have seizures. However, AS often has a certain EEG pattern. Pediatric neurologists trained in interpreting EEG can recognize this. 
• Genetic testing. This can confirm a diagnosis of AS. There are three types of useful genetic tests in AS: 

• • Methylation test. A methylation test can determine whether the UBE3A gene is functioning properly. 
  • Chromosome studies. There are different ways to look at a person’s chromosomes. Methods include karyotyping, fluorescence in situ hybridization (FISH), and chromosome microarray. These tests look at the shape and size of the chromosomes. They can show a difference in the area of the UBE3A gene. 
  • Sequence analysis. An analysis of the UBE3A gene can be helpful in diagnosis. It can determine whether there are any abnormalities that could cause Angelman’s disease. 

CAUSES

Angelman syndrome is a genetic disorder. It involves a region of chromosome 15. Although it is genetic, it does not have to be inherited from a parent. Usually, it is caused by random genetic changes. These occur very early in the development of an embryo. 

AS is associated with the UBE3A genes. The UBE3A genes are located on chromosome 15. Humans inherit one UBE3A gene from each parent. In AS, the UBE3A gene that comes from the mother is accidentally deleted.  

UBE3A makes a protein important to brain development. In most humans, the UBE3A gene from the father cannot make this protein. This means the UBE3A gene from the mother is essential for normal development. AS occurs when the mother’s copy is deleted. In these cases, there is no functioning gene copy.  

AS can have other causes, too. For instance, AS can result when:

• Both copies of chromosome 15 are inherited from the father instead of the mother  
• A mutated variant of UBE3A appears 
• The UBE3A gene is “turned off” through a process known as imprinting 
• The UBE3A gene is missing for any other reason 

AS is usually diagnosed through a clinical evaluation by a doctor. However, genetic testing can confirm AS.

There is no way to prevent AS. However, it can sometimes be diagnosed with genetic testing early in pregnancy. In vitro fertilization (IVF) allows eggs to be fertilized outside the body. In IVF, an embryo can be tested for AS before it is implanted.

TREATMENT AND THERAPIES

There is no cure for AS at this time. However, supportive care can help children survive and reach their potential. Important therapies include:

OUTLOOK

AS cannot be cured, and children will not grow out of it. They will require lifelong assistance and care.

People with AS will have difficulties with language. However, they may learn to use technology to communicate their needs and desires. Physical therapy can help with balance and walking.

People with AS can live as long as people without this syndrome. Some issues—like sleep problems—may improve with age.

RELATED DISORDERS

Disorders that can look similar to AS include:

• Rett syndrome. This is a genetic disorder that occurs exclusively in people with XX chromosomes (females). Rett syndrome can also result in:  
  • Cognitive impairment 
  • Language delay 
  • Seizures 

• Lennox-Gastaut syndrome. This is an epilepsy syndrome with multiple types of seizures. It has particular abnormalities (slow spike wave) on an EEG. A patient with AS may also have a diagnosis of Lennox-Gastaut syndrome if they present with these characteristics.  
• Mitochondrial encephalopathy. Mitochondria provide energy to the cell. Though they reside inside the cell, they contain their own genes. Variations in mitochondrial DNA can lead to cognitive impairment and seizures. 
• Gurrieri syndrome. This is a genetic disorder that can cause: 
  • Seizures 
  • Cognitive impairment 
  • Physical symptoms like short stature and atypical bone growth

Disorders also related to chromosome 15 include: 

• Prader-Willi syndrome. This is a genetic disorder. It involves deletion of the father’s copy of chromosome 15. Patients usually have: 
  • Low muscle tone (also called hypotonia) 
  • Initial struggles with feeding 
  • Constant hunger 
  • Excessive eating

Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. 

Research 

ClinicalTrials.gov for Angelman Syndrome (birth to 17 years).

These are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently.   

 ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.    

 Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits. 

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

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