Angelman Syndrome: Genetic Disorder

What's In This Guide?

    Angelman syndrome is rare but serious. It requires constant, lifelong care and while research is ongoing, not all that much is known about what’s at the root of the disorder. At YourDNA, we want to make sure you’re fully informed so you can make the best decisions for yourself and your family.

    Quick Overview

    Angelman syndrome is part of a class of genomic imprinting disorders. It’s very rare, only occurring in 1 in 12,000 to 20,000 people, though researchers believe that there are many undiagnosed cases which can lead to skewed statistics.

    While its cause is identified as a mutation or deletion in chromosome 15, researchers still don’t know what causes this mutation or deletion to happen in the first place. Patients with the disorder will need lifelong care and treatment of the symptoms which range from jerky movements to a severe intellectual disability that requires constant care.

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

    What Is Angelman Syndrome?

    Angelman syndrome, often referred to as AS or Happy Puppet Syndrome, is a genetic disorder that affects the nervous system.

    It’s named after the physician who pinpointed the disease and brought it to light in 1965.

    The disorder is congenital, meaning it’s present at birth, though it’s often not diagnosed until the child is between the ages of 6 and 12 months. At this stage, parents and pediatricians will likely notice delays in reaching specific milestones.

    The Angelman syndrome lifespan is that of a normal person, there’s usually no defining factor that makes for a shorter life. However, patients with the disorder will never be able to live independently, though they can thrive in a group environment and even learn how to do specific tasks.

    Angelman Syndrome Symptoms

    There are multiple symptoms associated with AS and they vary in severity. There are usually specific age ranges when these symptoms appear, as well, which is why it’s important to follow up with a doctor for regular wellness visits as scheduled.

    At birth, it’s not uncommon for the child to appear perfectly normal. The developmental delays don’t begin until 6 months and usually include failure to crawl or walk, and a lack of babbling that babies typically do at that age.

    Between the ages of 2 and 3, many patients with Angelman syndrome begin having seizures.

    Other symptoms that may indicate Angelman syndrome include, but are not limited to:

    • Excitable personality with frequent bouts of laughter
    • Intellectual disability
    • Ataxia
    • Jerky and/or stiff movements
    • Microbrachycephaly
    • Smaller head size
    • Hypopigmentation
    • Thrusting tongue
    • Atypical behaviors that include lifting arms while walking and flapping hands
    • Drooling
    • Crossed eyes
    • Problems sleeping

    If you notice that your child is exhibiting any of these symptoms, it’s a good idea to express your concerns with your pediatrician.

    Is Angelman Syndrome Hereditary?

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

    However, there are some rare cases of it being passed down, particularly by those who have a UBE3A gene mutation on chromosome 15.

    Is Angelman Syndrome a Dominant or Recessive Trait?

    For those who inherit the gene mutation noted above, it’s inherited in an autosomal dominant fashion.

    What Causes Angelman Syndrome?

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

    Everybody inherits a copy of the gene from both parents, but typically the maternal copy is the one that’s active in specific parts of the brain. Most cases of the genetic disorder occur when the maternal copy is damaged or missing.

    However, there are some rare instances of Angelman syndrome caused when patients inherit two paternal copies rather than one maternal and one paternal. This is known as paternal uniparental disomy.

    Can You Prevent Angelman Syndrome?

    Since the disorder is caused by a spontaneous gene mutation or deletion, there’s no way to prevent Angelman syndrome from occurring. Those who have a family history of the condition should speak with a genetic counselor before conceiving to see what the risks are of passing it down to their children.

    Diagnosis of Angelman Syndrome

    Diagnosing this genetic disorder requires a blood test. Doctors can identify certain traits that indicate Angelman syndrome, but without the blood test, there’s no way to confirm the diagnosis.

    How Do You Diagnose Angelman Syndrome?

    Several different blood tests will not only confirm the presence of Angelman syndrome, but can also indicate which type of deletion or mutation is causing the genetic disorder.

    How Do Doctors Test for Angelman Syndrome?

    The blood tests that doctors use to diagnose Angelman syndrome include DNA methylation, chromosomal microarray and UBE3A gene sequencing. Each of these looks for specific mutations that point to the disorder.

    The DNA methylation test looks at the parental DNA pattern and looks for the genetic abnormalities that cause the disorder. The chromosomal microarray, or CMA, lets lab technicians see if there’s a deletion of portions of the chromosome.

    With Angelman syndrome, a deletion of 15q11 to 15q13 is indicative of either this disorder or another similar one known as Prader-Willi. Finally, the UBE3A sequencing test can tell if there’s a mutation in the maternal copy of the gene.

    Angelman Syndrome and Genetics

    In most occurrences, Angelman syndrome is not a hereditary disorder so there’s minimal concern when considering genetics.

    With AS, the abnormality exists on chromosome 15, and this is only noticeable when developmental delays are discovered.

    Genetic Tests for Angelman Syndrome – Are They Available?

    Yes, there are genetic tests for Angelman syndrome, but they’re typically only available through a laboratory. Since it’s not something you can test positive as a carrier for, you won’t find an at-home DNA test that identifies the missing portion or mutation of the chromosome.

    What Laboratory Studies Should You Request to Help Confirm the Diagnosis?

    There are three laboratory studies that can help confirm the diagnosis and they are:

    • DNA methylation
    • Chromosomal microarray
    • UBE3A gene sequencing

    Each one of these tests can confirm the presence of AS, either alone or when completed together.

    DNA Testing to Spot or Detect Angelman Syndrome Early

    Since the diagnosis is often made while the patient is a baby, there’s no real need to test for the disorder prior to this. The only real way to detect it early is to undergo prenatal testing at the patient’s request.

    Most people, however, don’t consider this unless there’s a family history of the disorder and prenatal testing doesn’t routinely look for the disorder because it’s so rare.

    Testing For Angelman Syndrome on a Pregnancy or Before a Pregnancy Is Achieved

    If you’re pregnant or someone in your family has Angelman, it’s natural to be cautious. However, it’s important to note that the chance of the disorder being passed down to children is very rare.

    However, speaking with a genetic counselor can help determine your risks prior to pregnancy, and if you’re already pregnant, you can ask your obstetrician to order the necessary tests. There are two methods available: 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.

    DNA Tests Currently Available for Angelman Syndrome Include:

    As aforementioned, there are three DNA tests currently available that your doctor may order and they include different methods of identifying whether or not the patient has AS.

    Where Can I Go For a Genetic Test?

    Currently, the only place you can go for a genetic test to look for the mutations or deletions associated with Angelman syndrome is to your child’s pediatrician. If they suspect the disorder is responsible for their symptoms, they will order the test and most times, your insurance will cover the testing.

    It’s possible to order DNA sequencing outside of a doctor’s office, but it tends to very pricey. Additionally, insurance companies typically don’t cover the cost unless the request comes from a physician associated with your child’s care.

    DNA Testing For Angelman Syndrome: Strengths and Limitations

    It’s not uncommon for tests to come with specific strengths and limitations. When it comes to DNA testing for Angelman syndrome, the strength lies within the methods of testing and identifying the exact cause of the occurrence.

    This can help parents determine whether it’s likely to occur in the future, such as being passed down to children.

    Another strength is that it can help parents seek out the proper treatment once they receive the diagnosis. They can also set up future care for when they’re no longer around.

    The biggest limitation when it comes to DNA testing for AS comes in the fact that there’s nothing that can be done to prevent or cure the disorder when it’s identified. Parents can only seek treatment for the symptoms.

    Who Does Angelman Syndrome Typically Affect?

    Angelman syndrome doesn’t appear to discriminate, affecting males and females equally with no ethnic predisposition.

    Since it’s congenital, it’s diagnosed early in infants and babies.

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

    This is a tricky question to answer simply because there is no one answer. The truth is the chances depend on the actual cause of the disorder.

    Doctors and genetic counselors have to pinpoint the specific mutation or deletion responsible for the disorder and then evaluate the risk based on that fact.

    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. However, due to the severity of the intellectual disability and the inability to care for themselves, there is a very high possibility that they will not be able to care for a child properly. This is a consideration that needs to be kept in mind.

    Angelman Syndrome Treatment Options

    Is Angelman Syndrome Treatable?

    When it comes to the disorder itself, AS is not treatable. However, doctors can regularly manage the symptoms to keep the patients comfortable and able to lead as normal a life as possible. There are multiple treatment options that may be a regular part of a patient’s life, including:

    • Anti-seizure medications
    • Various therapies
      • Communication
      • Physical
      • Behavior

    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.

    The Prognosis for Angelman Syndrome

    The prognosis for Angelman syndrome is relatively positive. Despite the fact that there may be severe intellectual disability, a patient can have a good quality of life with proper management of the symptoms.

    The good news is there is typically no developmental regression as they grow older.

    Does Angelman Syndrome Go Away?

    No, AS is a lifelong disorder that requires constant care, particularly that of an assisted living center if there’s no family around since people with the syndrome cannot live independently.

    Is There a Cure for Angelman Syndrome?

    No, as of 2019 there is no cure for the disorder, though there are ongoing clinical studies. Researchers continue to explore AS and its genetic occurrence to determine whether there’s a way to prevent or cure the disorder in the future.

    What Are Angelman Syndrome Care Options?

    The main care option for Angelman syndrome patients is the treatment of the existing symptoms. This can include medication, therapies or a combination thereof.

    However, it’s important to seek out long-term care for the patient because once there are no more family members to help care for them, they will need to be in a facility where they get the support they need. Intellectual disabilities and seizures make it difficult for them to live independently.