Angelman Syndrome: Genetic Disorder Diagnosis and More

Updated September 9, 2020

Latest Revision: September 9, 2020

Author and Contributing Experts to this Guide include:

Brenna Bentley Patient Education, Genetic Counselor LinkedIn

Angelman syndrome (AS) is a genetic disorder affecting chromosome 15. It's very rare, only occurring in 1 in 12,000 to 20,000 people 1, though researchers believe there may be many undiagnosed cases.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic. Read More...

Patients with the disorder will need lifelong care and treatment of their symptoms which range from jerky movements to severe intellectual disability.

Despite this, however, many patients have a long lifespan with good quality of life.

What Is Angelman Syndrome?

Angelman syndrome is a genetic disorder that affects the nervous system. It's named after the physician, Dr. Harry Angelman, who identified the disease in 1965 2.

The disorder is congenital, meaning it's present at birth. Most children start showing symptoms between the ages of 6 and 12 months of age.

At this stage, parents and pediatricians will likely notice delays in reaching specific milestones 3.

The lifespan of a person with Angelman syndrome is unaffected. However, patients with the condition would not be expected to live independently, though they can thrive in a group environment.

Who Does Angelman Syndrome Typically Affect?

Angelman syndrome does not impact certain ethnicities more than others, and both males and females are seen to be equally affected 4.

Angelman Syndrome Symptoms

There are multiple symptoms associated with AS and they vary in severity between people.

The most common symptoms tend to appear at specific age ranges, making it important to follow up with a doctor for regular wellness visits as scheduled.

At birth, it's not uncommon for a child to show no concerning signs. The first symptoms may not begin until 6 months and usually include failure to crawl or walk, and a lack of babbling common to babies of that age.

In mild cases children will learn to walk between the ages of 2 to 3 5, and in 15% of severe cases children may never walk on their own 6.

In early childhood, more than 80% of children with Angelman syndrome begin having seizures 7 8.

Other behaviors or traits that may suggest Angelman syndrome include, but are not limited to 9:

Most common; seen in nearly all patients 10:

  • Excitable personality with frequent bouts of laughter
  • Learning delays
  • Poor coordination
  • Jerky and/or stiff movements
  • Lifting arms and flapping hands while walking

Less common, but still frequently seen 11:

  • Problems sleeping
  • Fascination with water or crinkly items
  • Mouthing behavior

Other physical findings or unique aspects of how children with AS look can include 12 13:

  • Small head that is flat at the back
  • Lighter skin patches compared to the rest of the skin
  • A tongue that sticks out
  • Crossed eyes

What Other Complications Can Occur?

Certain complications may occur due to some of the features of Angelman syndrome. These can include 14 15:

  • Feeding difficulties for infants
  • Short attention span and hyperactivity
  • Disruptive behavior
  • A curved spine
  • Problems sleeping
  • Obesity

What Causes Angelman Syndrome?

The main cause of Angelman syndrome is a genetic change or deletion of the ubiquitin protein ligase E3A gene, also known as UBE3A. This is located on the long arm of chromosome 15 16.

Everybody inherits one copy of the gene from each parent, giving us 2 total copies of UBE3A. However, only the copy of the gene that came from our mother is active in parts of our brain.

If something happens to the UBE3A gene that came from mom, our body is missing an important piece of genetic instructions. The UBE3A from our father can’t make up for the missing copy from the mother. Most cases (70%) 17 of the Angelman syndrome occur when the maternal copy is missing.

Some cases (10%) 18 occur due to a genetic change in the UBE3A copy that came from the mother. When the correct DNA sequence has changed, the gene cannot carry out its normal job. 

There are some rare instances (5%) 19 of Angelman syndrome caused when a child inherits two paternal copies rather than one from each parent. This is known as paternal uniparental disomy, or UPD. 

Can You Prevent Angelman Syndrome?

Since the condition is caused by a spontaneous genetic event, there's no way to cause or prevent Angelman syndrome from occurring.

Those who have a family history of the condition should speak with a genetic counselor before getting pregnant to see what the risks are of passing it down to their children.

Is Angelman Syndrome Passed Down Through Families?

In short, not always. Angelman syndrome typically occurs with no prior family history of the condition.

However, there are some rare cases of it being passed down, particularly by those who have a non-working copy of the UBE3A gene on chromosome 15 20. For those who inherit the non-working gene, it's inherited in an autosomal dominant fashion.

This means that there’s a 50/50 chance of passing down the same genetic change to future children. 

If I Have a Child With Angelman Syndrome, What Are the Chances That Future Children Will Inherit it as Well?

There is no one answer. The chances depend on the type of genetic change that happened.

If Angelman syndrome occurred in a child due to a random event, and wasn’t an inherited form, the chance of this happening again in the same couple is <1% 21.

A genetic counselor can talk with you about the genetic change in a child with the condition. Based on this information they can discuss the chances of it happening again. 

Can People With Angelman Syndrome Have Children in the Future?

Currently, there's no reason to believe that people with Angelman syndrome cannot get pregnant or have children in the future.

Diagnosis of Angelman Syndrome

Diagnosing this condition requires a genetic test using a blood sample. Doctors can identify certain traits that suggest Angelman syndrome, but the blood test is needed for confirmation.


How Do You Diagnose Angelman Syndrome?

A doctor may suspect Angelman syndrome based on the way a child acts or looks. To confirm a diagnosis a genetic test is needed.

There are several different types of genetic tests that can be done. A geneticist or genetic counselor will know which type of test to use based on how they think the condition arose. 

How Do Doctors Test for Angelman Syndrome?

The blood tests that doctors can use to diagnose Angelman syndrome include DNA methylation, chromosomal microarray and UBE3A gene sequencing 22. Each test is looking to see if the UBE3A gene is working as expected, but they use different technology.

We need to have different testing technologies because AS can come about in different ways. 

The DNA methylation test looks at the UBE3A gene to see which parent provided the gene 23. Since AS occurs if the copy of UBE3A from the child’s mom is missing, the test can tell us if only a copy from the child’s dad is present.

Sometimes a child still has 2 full copies of UBE3A, but they are both shown to be from the father based on a DNA methylation test. Understanding the results of a DNA methylation test can be complicated and requires a genetics doctor.

A genetic counselor can help explain the results and what the results mean for future pregnancies or children. 

The chromosomal microarray can tell if one copy of the UBE3A gene is missing on one chromosome 24. Even if we know the gene is missing, a DNA methylation test would also be needed to figure out if the missing copy was from the child’s mother or father.

In AS, the missing copy would have been from the mother. If the missing gene was from the father, this would actually be a different condition called Prader-Willi.

Finally, the UBE3A sequencing test can tell if there's a mistake in the in the maternal copy of the gene that prevents it from working as expected 25.

Where are DNA Tests for Angelman Syndrome Available?

Only your child’s pediatrician or other medical professional can order a DNA test for Angelman Syndrome. This is not a condition that you will see as part of an at-home DNA test.

Testing For Angelman Syndrome Before Birth

If you're pregnant or someone in your family has Angelman, it's natural to wonder if your baby could be affected. 

You can ask your primary care provider for a referral to a genetic counselor. Before testing a pregnancy, we need to already have test results from an affected family member.

This helps make sure that we’re choosing the most appropriate testing. 

There are two diagnostic methods available for prenatal diagnosis: amniocentesis and chorionic villus sampling (CVS). Both involve extracting fluid or tissue from the uterus and carry a small risk to the pregnancy.

However, they can provide answers and help you prepare for the future.

Non-invasive prenatal screening (NIPS) offers a different approach to assessing risk for AS in a pregnancy. NIPS uses a blood draw from the mother, eliminating direct risk to the fetus.

NIPS is a screen, meaning the results provide a risk figure and are not diagnostic. These results can tell you whether your pregnancy is at a low risk or an elevated risk to be affected by AS.

At least one laboratory currently offers a NIPS panel that includes evaluation of AS 26.

Working closely with a prenatal genetic counselor can help a family understand testing options related to high-risk pregnancies. Learning about the type of results available and receiving education and proper consent before a test is ordered is a key part of genetic testing. 

Benefits and Limitations of DNA Testing

It's not uncommon for tests to come with specific benefits and limitations. 

Testing for AS can help parents understand the cause and whether it's likely to occur again in future children. This can be important information to share with family members who may also be at risk. 

Another benefit is that it can help parents seek out the proper treatment once they receive the diagnosis. The earlier a child begins treatment and interventions, the greater chance they have of reaching their fullest potential. 

The main limitation when it comes to DNA testing for AS is that there’s currently no cure. While testing and receiving a diagnosis can have a large positive impact on the health of the child, we are only able to manage symptoms. Healing the underlying cause is not possible at this time. 

Angelman Syndrome Treatment Options

Can Angelman Syndrome Be Treated?

Doctors can provide treatments and medications to manage the symptoms to keep patients comfortable and able to take part in daily activities.

There are multiple treatment options that may be a regular part of a patient's life, including 27:

  • Anti-seizure medications
  • Communication therapy
  • Physical therapy
  • Behavioral therapy

Each of these is likely to be part of every AS patient's life at some point in time, though the severity of the symptoms may vary widely. The response to the therapies and medications may vary as well, so it's important to develop an open line of communication with your doctor.

What is the Prognosis for Angelman Syndrome?

The prognosis for Angelman syndrome is relatively positive and patients can expect a standard lifespan.

Patients can have a good quality of life with early intervention and proper management of the symptoms 28.

Does Angelman Syndrome Go Away?

No, AS is a lifelong condition. Symptoms usually remain constant and do not get worse over time. Extra care throughout life is needed, sometimes that of an assisted living center. 

Is There a Cure for Angelman Syndrome?

No, there is no cure for the condition, but there are ongoing clinical studies and research efforts to identify new therapies.

Where can I get support if my family is affected by Angelman Syndrome?

There are many valuable support groups that meet both in person and virtually.

Some groups may have structured meetings, and some may communicate through an online message board or social media platform.

Regardless of the venue, finding support from families who truly know what you are going through can be very helpful. Support groups can offer advice for specific questions, help you to anticipate what will happen as your child grows, or just be an empathetic listening ear when you need someone to talk to.

Below are some links to patient support organizations for Angelman syndrome.

Referenced Sources

  1. Kleman M. On the prevalence of Angelman syndrome. Am J Med Genet. 1995;59(3):405.
  2. Clayton-Smith, J., & Laan, L. (2003). Angelman syndrome: a review of the clinical and genetic aspects. Journal of Medical Genetics, 40(2), 87–95. https://doi.org/10.1136/jmg.40.2.87
  3. NORD (National Organization for Rare Disorders). (n.d.). Angelman Syndrome. Retrieved July 17, 2020, from https://rarediseases.org/rare-diseases/angelman-syndrome/
  4. Dagli, A. I., Mueller, J., & Williams, C. A. (1993). Angelman Syndrome. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews®. Seattle (WA): University of Washington, Seattle. Retrieved from Angelman Syndrome
  5. Clayton-Smith, J., & Laan, L. (2003). Angelman syndrome: a review of the clinical and genetic aspects. Journal of Medical Genetics, 40(2), 87–95. https://doi.org/10.1136/jmg.40.2.87
  6. Clayton-Smith, J., & Laan, L. (2003). Angelman syndrome: a review of the clinical and genetic aspects. Journal of Medical Genetics, 40(2), 87–95. https://doi.org/10.1136/jmg.40.2.87
  7. Bird, L. M. (2014, May 16). Angelman syndrome: review of clinical and molecular aspects.
  8. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  9. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  10. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  11. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  12. Clayton-Smith, J., & Laan, L. (2003). Angelman syndrome: a review of the clinical and genetic aspects. Journal of Medical Genetics, 40(2), 87–95. https://doi.org/10.1136/jmg.40.2.87
  13. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  14. Bird, L. M. (2014, May 16). Angelman syndrome: review of clinical and molecular aspects.
  15. Williams, C. A. (2005). Neurological aspects of the Angelman syndrome. Brain and Development, 27(2), 88–94.
  16. Lalande, M., & Calciano, M. A. (2007). Molecular epigenetics of Angelman syndrome. Cellular and Molecular Life Sciences: CMLS, 64(7–8), 947–960.
  17. Lalande, M., & Calciano, M. A. (2007). Molecular epigenetics of Angelman syndrome. Cellular and Molecular Life Sciences: CMLS, 64(7–8), 947–960.
  18. Lalande, M., & Calciano, M. A. (2007). Molecular epigenetics of Angelman syndrome. Cellular and Molecular Life Sciences: CMLS, 64(7–8), 947–960.
  19. Lalande, M., & Calciano, M. A. (2007). Molecular epigenetics of Angelman syndrome. Cellular and Molecular Life Sciences: CMLS, 64(7–8), 947–960.
  20. Lalande, M., & Calciano, M. A. (2007). Molecular epigenetics of Angelman syndrome. Cellular and Molecular Life Sciences: CMLS, 64(7–8), 947–960.
  21. Williams, C. A., Driscoll, D. J., & Dagli, A. I. (2010). Clinical and genetic aspects of Angelman syndrome. Genetics in Medicine, 12(7), 385–395.
  22. Ramsden, S. C., Clayton-Smith, J., Birch, R., & Buiting, K. (2010). Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Medical Genetics, 11(1), 70.
  23. Ramsden, S. C., Clayton-Smith, J., Birch, R., & Buiting, K. (2010). Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Medical Genetics, 11(1), 70.
  24. NORD (National Organization for Rare Disorders). (n.d.). Angelman Syndrome. Retrieved July 17, 2020, from https://rarediseases.org/rare-diseases/angelman-syndrome/
  25. Ramsden, S. C., Clayton-Smith, J., Birch, R., & Buiting, K. (2010). Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Medical Genetics, 11(1), 70.
  26. Martin, K., Iyengar, S., Kalyan, A., Lan, C., Simon, A. L., Stosic, M., Kobara, K., Ravi, H., Truong, T., Ryan, A., Demko, Z. P., & Benn, P. (2018). Clinical experience with a single-nucleotide polymorphism-based non-invasive prenatal test for five clinically significant microdeletions. Clinical Genetics, 93(2), 293–300.
  27. DYSCERNE, A. S. G. D. (2010, January 24). Management of Angelman Syndrome: A Clinical Guideline. Retrieved from Orpha.net
  28. Dagli, A. I., Mueller, J., & Williams, C. A. (1993). Angelman Syndrome. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews®. Seattle (WA): University of Washington, Seattle. Retrieved from Angelman Syndrome