FAQ

Angelman syndrome (AS) and autism spectrum disorder (ASD) share some similarities in behavior, but they are distinct conditions with different causes. AS has been referred to Autism-adjacent

While some children with Angelman may also show signs of autism, diagnosing them with ASD would require a thorough evaluation by a specialist in autism, who would look for additional markers specific to ASD that are not a direct result of Angelman syndrome.

In Ireland, there are many services supporting people with ASD as well as specialist ASD preschools and primary school classes. Some families feel that an ASD diagnosis has helped their child with the additional resources available.

In addition, due to the common traits like sensory processing difficulties, ASD resources and advice can be incredibly useful to families.

Not everyone with Angelman Syndrome (AS) will experience epilepsy, but seizures are very common in individuals with the condition. Approximately 80-90% of individuals with AS are affected by epilepsy at some point in their lives, typically beginning in infancy or early childhood.

The type, frequency, and severity of seizures can vary greatly between individuals. Some may experience only occasional seizures that are well-controlled with medication, while others might have more frequent or challenging seizures.

96% of epilepsy in del+ genotype will occur before age of 5

Clinical Characterization of Epilepsy in Children With Angelman Syndrome, Cassater, Daiana et al.

In most cases, Angelman syndrome is not inherited. It is a result of a de novo (new) genetic event, meaning the mutation or deletion typically occurs for the first time in the affected child and is not passed down from the parents. However, there are rare instances when a parent carries a balanced chromosomal rearrangement (such as a translocation) that could increase the risk of passing on an altered version of chromosome 15.

Risk of Recurrence in a Sibling

Since AS is often caused by a de novo deletion or mutation, the risk of recurrence in a sibling is generally low. The chance of a second child being affected depends on the specific genetic cause of the AS in the first child:

1. If the cause is a de novo deletion: In most cases, there is no increased risk for future siblings, as the deletion typically happens randomly. The recurrence risk would be less than 1%.
2. If the cause is uniparental disomy (UPD): In this case, the parents are not carriers of the genetic change, and the recurrence risk is still low—usually around 1-2%.
3. If one parent is a carrier of a balanced chromosomal rearrangement (such as a translocation involving chromosome 15), the risk of recurrence in future pregnancies can be higher. In this situation, genetic counseling and testing can help estimate the recurrence risk more precisely.

What to Do if You Have Concerns About Recurrence

If you are concerned about the risk of Angelman syndrome in future pregnancies, it is helpful to consult with a genetic counselor in Crumlin Children’s hospital. A genetic counselor can assess the family history, discuss the specific genetic cause of AS in your child, and offer guidance on testing and recurrence risks for future children.

If there’s any chance that a balanced translocation or another inherited genetic factor could be involved, the counselor might recommend testing for both parents to determine whether one is a carrier.

Can angelman syndrome be detected in pregnancy?

Non-invasive prenatal screening (NIPS, also known by the brand name Natera Panorama) does not typically test for AS. Some NIPT providers may offer more expanded genetic panels that include a wider range of conditions, possibly including rare syndromes like Angelman syndrome, if specifically requested.

Amniocentesis and Chorionic Villus Sampling (CVS)

Both amniocentesis and CVS can be used to obtain fetal cells for genetic analysis. These diagnostic tests can detect deletions or mutations in the UBE3A gene, which causes Angelman syndrome. Amniocentesis is usually performed after 15 weeks of pregnancy, and CVS is typically done between 10 and 13 weeks.

• Amniocentesis: A sample of amniotic fluid is taken, which contains fetal cells for analysis.
• CVS: A small sample of the placenta is taken for genetic testing.

These tests can provide a definitive diagnosis of Angelman syndrome, but they carry a small risk of miscarriage, so the decision to proceed with them depends on the individual situation, such as a family history of Angelman syndrome or abnormal screening results.

The deletion+ genotype of Angelman syndrome is a phenomenon – because even though the disorder is based one one missing gene UBE3A… a del+ person can be missing up to 5-6 million base pairs of DNA.

So if all that DNA is missing – what are the other genes that are important?

In 2024s FAST Global Summit on Angelman Syndrome, Allyson Berent presented on some of these findings and indicated 2 genes that may be impacting on AS symptoms.

• GABRB3 – linked to epilepsy, ASD and Intellectual Disability
• GABRG3 – linked to sleep duration

Go watch this amazing video from FAST to find out more!