What Is Angelman Syndrome? 

Overview

Many health conditions are named after the doctors who first described them. Angelman Syndrome (AS) is one example of this practice.¹ Such names do not tell you much about the disease and might leave you confused if your child is diagnosed with it. So, if you want to learn more about AS, you are in the right place to get the information you need.

AS is a rare genetic condition that changes how nerve cells (neurons) in your brain and spinal cord develop and function. This leads to a range of physical and learning disabilities.¹ AS is named after Dr. Harry Angelman, the paediatrician (a medical doctor specialising in children and their diseases) who first described the characteristic symptoms of the condition in children.¹ It arises due to changes in a gene called ubiquitin-protein ligase E3A (UBE3A).²

People with AS have a normal life expectancy but require extra support due to their disabilities. There is currently no cure for AS, but the right supportive care can improve the quality of life for affected people and their families.¹

If your child has been diagnosed with AS or if you are interested in learning more about the condition and how it might affect your family, keep reading to discover valuable information and the potential support that can be helpful.

What causes angelman syndrome? 

AS is attributed to a genetic mutation within the UBE3A gene (a segment of DNA that contains the instructions needed to produce a protein).¹ The UBE3A gene contains the instructions required to make a  protein ( a molecule that has certain functions within our cells) called ubiquitin-protein ligase E3A, which is needed for neurons to function normally.²  

We all inherit two copies of each gene. One copy comes from our mother (maternal copy), and the other from our father (paternal copy). Our cells use information from both copies, but in a small number of genes, only one copy is active while, the other is switched off shortly after conception, leading to genetic imprinting.³ 

Normally, only the maternal copy of the UBE3A gene is active in the brain. AS is caused by mutations or deletions (missing) of the maternally inherited UBE3A gene.¹ Since the paternal copy of UBE3A is switched off and the maternal copy is either missing or mutated, neurons lack the necessary ubiquitin-protein ligase E3A they need. As a result, this impacts their development and function, ultimately leading to the symptoms of AS.⁴

Most people with AS have unaffected parents. The change in the copy of UBE3A inherited from their biological parents occurs shortly after conception.⁵

What are the signs and symptoms of angelman syndrome?

Developmental delay

Children with AS reach milestones such as crawling and walking later than other children. Some children are not able to walk on their own and may require long-term use of a wheelchair. Children who are able to walk may have a stiff, wide-based way of walking. Usually, signs of developmental delay are evident by the age of six months.¹

Neurological symptoms

Approximately 80% of children with AS will experience seizures between two and three years of age. Children often have impaired balance and coordination and may experience stiff or jerky movements (sudden, irregular movements). In addition, muscle tone may be reduced.^{1, 5}

Communication problems

Children with AS have reduced or no speech.¹

Behavioural symptoms

AS can result in a range of characteristic behaviours. Children are often happy and excitable and tend to smile or laugh frequently. Attention span is generally reduced and children may show obsessive tendencies.¹ Other behavioural symptoms, such as hyperactivity and hand flapping, are not unusual.⁵

Sleep problems

Most children with AS experience problems with their sleep and may wake up frequently during the night.⁵ These tend to improve with age.¹ 

Characteristic facial features

Children with AS tend to have some characteristic facial features, such as:¹ 

• Microcephaly (small head size) 
• Macroglossia (large tongue that may stick out of their mouth)
• A wide mouth with widely-spaced teeth
• A pronounced lower jaw
• A thin upper lip
• Strabismus (crossed eyes) 

It is important to remember that not all children with AS will show all the above symptoms and that features can vary between affected children.⁵ Speak to your paediatrician if you want to discuss your child’s individual symptoms in more depth. 

How is angelman syndrome diagnosed? 

If your healthcare team suspects that your child may have AS, the diagnosis will typically involve the following aspects:

History and examination

Your healthcare providers will take a detailed history of your child's development and health. This includes evaluating any other health problems your child may have, examining your family's medical history, and reviewing any medications your child is currently using. A physical examination will be conducted to identify the characteristic features of AS described above. Additionally, your child’s behaviour, language abilities, and motor skills will also be assessed.⁵

Genetic testing 

If AS is suspected, it is likely that your child's healthcare provider will use a specialised blood test to confirm the diagnosis. In the laboratory, scientists can then look for changes in the UBE3A gene that would support the diagnosis of AS.⁵

How is angelman syndrome managed?

Although there is currently no cure for AS, the right support can allow your child and your whole family to enjoy a good quality of life.¹ If your child is diagnosed with AS, they may benefit from the following: 

Medication

Medication can be used to manage the symptoms of AS. The commonly used medications include:

• Anti-seizure medications (anticonvulsants)

Seizures can be distressing for the whole family. Fortunately, there is a wide range of medications that can reduce the severity and frequency of seizures, and terminate seizures when they do occur.⁶

• Medications to support sleep

In addition to adhering to strict bedtime routines, melatonin can help your child enjoy a restful sleep.⁵ Melatonin is a hormone that is released naturally by the brain to induce sleep at nighttime.⁷

• Medications to manage gastrointestinal symptoms

Approximately 45-65% of children with AS suffer from acid reflux or constipation. If this is the case, then treatment with medications to regulate stomach acid and laxatives can offer relief.⁵ 

Most behavioural symptoms associated with AS can be managed without medications. However, if symptoms are causing significant impairment, drug therapy may be considered.⁵ Talk to your healthcare provider if your child’s behaviour is causing you concern.

Specialist therapy from allied health professionals

Physical, occupational, and speech therapists have an important role to play in the management of AS.⁵

• Physical therapy

Physical therapy can help to improve your child’s functional abilities and promote overall physical well-being.⁸ The right regimen of exercises and activities can help your child build muscle strength, improve coordination, and reduce stiffness.¹  Additionally, a physical therapist can recommend any aids or devices that may support your child's movement.⁵

• Occupational therapy

An occupational therapist can work with you and your child to develop strategies and adaptations to promote your child's independence.⁸ They may work on improving your child's motor skills, enabling them to engage in everyday activities more effectively. Moreover, an occupational therapist may suggest modifications to the home or school environment that could promote safety and independence for your child.⁵

• Speech therapy

Working with a speech therapist can help your child communicate more effectively.⁵ If verbal speech is limited, there are a range of aids and assistive devices that can provide alternative means of communication for your child.⁸ 

What is the outlook for my child with angelman syndrome?

People with AS generally have a normal life expectancy.¹ However, AS is a lifelong condition, so your child will require some extra support over the course of their life. For some people, it may be possible to live apart from family in adulthood, whilst others will need more intensive support.⁹ 

Frequently asked questions

How common is angelman syndrome? 

Approximately 1 in every 12,000 to 20,000 babies is estimated to be born with AS.⁹

I have a child with angelman syndrome, and I want to have another baby. Will they also be affected? 

Most cases of AS occur randomly in the population, and the risk to subsequent children is therefore low.¹ Occasionally, the condition can be inherited from a parent and thus run in the family. A genetic counsellor can help you understand more about the specific genetic change causing AS in your child and discuss the risk that exists for subsequent pregnancies.⁵ 

Are there any patient support organisations for families affected by AS? 

There are a number of patient support organisations around the world. Below, you will find a list of some of these organisations. Talk to your healthcare provider if you are looking for a patient support organisation in your country.

• United Kingdom: Angelman UK
• USA: Angelman Syndrome Foundation
• Ireland: http://www.angelman.ie/
• India: Angelman Foundation India
• Australia: ASA Australia

Will there ever be a cure for AS?

Ongoing research is aiming to find a treatment that can potentially cure or modify the progression of AS. One promising avenue involves reactivating the silenced UBE3A copy. This reactivation could compensate for the missing or defective copy inherited from the parent. Currently, several approaches are under investigation to achieve this goal.¹

Summary

Angelman syndrome (AS) is a rare genetic condition caused by changes in a copy of the UBE3A gene inherited from a parent. Symptoms typically become noticeable within the first year of a child's life, often with delays in reaching developmental milestones. The majority of AS cases occur randomly in the population, but in rare instances, AS can be inherited within families. 

AS is characterised by delayed development, movement disorders, speech impairment and behavioural problems. Diagnosis typically includes a combination of clinical assessment and genetic testing. Although there is no cure for AS, multidisciplinary supportive care can help to improve the quality of life for affected children and their families.