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Angelman Syndrome 

1. What is Angelman syndrome (AS)?

  • AS is a rare condition that occurs in approximately 1:15,000                                                                  

  • It affects the 15th chromosome resulting in a severe reduction of expression of the

      gene UBE3A in the brain. UBE3A (Ubiquitin Protein Ligase E3A) is a Protein Coding gene.

  • AS is not a degenerative condition. With a healthy and well managed lifestyle, individuals

      with AS have a normal life expectancy but will require life-long care.

  • AS affects males and females of all racial/ethnic groups, equally.     


In brief, Angelman syndrome is a neuro-genetic disorder that affects the nervous system causing

physical and intellectual impairments. A ‘syndrome’ means a group of recognisable characteristics

occurring together.

                                                                                                                                                                                             Dr Harry Angelman 

In the 1960s, English paediatrician, Dr Harry Angelman recognised a common set of unusual

characteristics in 3 children. He published a medical paper in 1965 documenting his observations.

It was only in the early 1990s that genetic testing was developed for what is now known as 

Angelman syndrome. Read more on the History of AS research here.  

Handy Resources

Facts About Angelman Syndrome -  (ASF)

Management of Angelman Syndrome A Clinical Guideline - DYSCERNE


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2. What causes Angelman Syndrome?

Angelman Syndrome is caused by a severe reduction of expression of a single gene UBE3a in the brain. UBE3A is a ubiquitin ligase whose function and targets relevant to AS are still unknown. AS occurs through 4 different genetic mechanisms, all involving chromosome 15. In about 80% of cases clinical diagnosis can be confirmed by laboratory testing. Most cases are sporadic but some genetic mechanisms have implications for other family members. 

  1. Deletion+ (15q11.2-q13 deletions), 68% of cases – the majority of AS cases are caused by deletions on the maternal copy of Chromosome 15.

  2. UBE3A mutations, 11% of cases – Mutations in the UBE3A gene either prevent its expression or function, thus these individuals do not have the appropriate levels of functional UBE3A in the brain.

  3. Uniparental disomy, UPD; 7% of cases –The individual has two copies of paternal Chromosome 15.

  4. Imprinting defect, ICD, 3% of cases – A deletion of the imprinting centre on Chromosome 15. Could also be caused by loss of imprinting information during the mother’s oogenesis.

  5. Clinical/other, 11% – When all testing for Angelman Syndrome is negative but they still meet the diagnostic criteria for AS. These individuals may have as yet unrecognized mutations that affect UBE3A or genomic imprinting on Chromosome 15.


The following links explain the clinical, genetic make-up and causes of Angelman syndrome in greater detail:


3. Characteristics of Angelman Syndrome

The disorder is characterized by global developmental delays, severe speech impairment and a movement/balance disorder. Many have a seizure disorder, which at times can be difficult to treat. Most children with AS seem to need very little sleep when young, and are usually very sociable and display a very happy demeanour.

People with AS may have some physical features in common but they also closely resemble their parents and family. While some characteristics of AS are directly attributed to the syndrome, any one person will only have some of them. It is often noted that fair skin, blonde hair and blue eyes is common, however there are also many people with brown eyes, dark skin and dark hair, who have a diagnoses of AS.

It is important for professionals to note that each person who has AS is an individual. Just like all other children, every person who has AS has their own unique appearance and personality and vary greatly in their abilities, talents, weaknesses, and achievements. Because of these differences, treatments, therapies and management will also vary from case to case. The extent to which a child shows the physical characteristics of the syndrome is no indication of his/her intellectual capacity.


Even though someone with Angelman syndrome cannot speak, they communicate using many other modes of communication. They are also able to hear your words, tone and attitude. They deserve the same respect as everyone else and we always assume competence. The Angelman Network advocates for full inclusion in NZ. Read more...

4. Common Traits 

  • In infancy and early childhood, many experience feeding complications and appear to require very little sleep.

  • Epilepsy occurs in approx. 80% of cases, usually beginning at around 2 years of age. Read more...

  • The syndrome causes a severe speech impairment (many have no words at all) and delays in development and learning. Access to a robust language system (AAC) from as early as possible is now opening new ways for expressive language development, literacy and numeracy. Read more…

  • Most people with AS tend to be very sociable, happy, and at times, over excitable. They frequently display what appears to be a happy demeanour however, the smiles and laughter can also express other feelings, such as anxiety, fear, and even pain.

  • Essentially all young children with Angelman syndrome have a component of hyperactivity. Attention span can be so short that social interaction and communication is adversely affected. Persistent and consistent behaviour modification can help decrease these behaviours. Observations in young adults suggest that hyperactivity decreases with age. Most children with Angelman syndrome do not receive drug therapy for hyperactivity, although some may benefit from the use of medications such as methylphenidate (Ritalin). Use of sedating agents is not recommended.

      Read more here: Hyperactivity in Angelman Syndrome

  • A strong attraction for water, music, lights and reflections can be common early on and water can therefore pose a potential accident risk.

  • Ataxia: Ataxia is a movement/balance disorder that results in an unusual gait and jerky movements.


Diagnostic criteria are based both on clinical features and on the currently available genetic information. Clinical diagnosis is difficult in the first two to three years of life. Conditions with a similar initial presentation are Rett syndrome, Lennox Gastaut syndrome, Autism and non-specific Cerebral Palsy. Based on the NZ population there could be approximately 300 people in NZ with AS, yet many remain undiagnosed or possibly even misdiagnosed with Autism, Cerebral Palsy (CP) or global developmental delay (GDD).

5. Related Conditions and Complications

Not all the conditions listed below are applicable to every individuals who has AS. Not all individuals will have epilepsy, some might sleep really well, many have no behaviours that require management, and some might only have mild problems with reflux and constipation. However when the following conditions are present they need to be carefully monitored and managed. Some of these conditions can cause pain, stress and disruptions to family life and can even become life threatening if not treated appropriately. 

1.  Epilepsy

     read more here

2.  Sleep Disorder:

  •  “...Serious sleep disorders are one of the symptoms of AS. These can be so serious that the children must sleep in special crib-like beds to keep them from wandering or harming themselves at night.” Read more here: Circadian clock linked to Angelman syndrome

  • “…A significantly high frequency of disorders of initiating and maintaining sleep, prolonged sleep latency, prolonged wakefulness after sleep onset, high number of night awakenings and reduced total sleep time were found in our AS patients, as compared to age-matched controls. We also found other types of sleep disorders, never reported before, such as enuresis, bruxism, sleep terrors, somnambulism, nocturnal hyperkinesia, and snoring.” Read more here: Sleep disturbances in Angelman syndrome: a questionnaire study 

  • Review, Sep 2020 study: Angelman syndrome and melatonin: what can they teach us about sleep regulation. Read full article here. 

  • “…According to Angelman-related literature, sleep problems with our children can’t just be put to bed. The degree to which sleep evades children with AS is enormous, and can include everything from difficulties with falling asleep to reduced sleep time, bedwetting, waking during the night, terrors, and even sleep walking. Like typical children, youngsters with AS also don’t like to stay in bed and often try to escape their beds or rooms to seek stimulation via toys, electronics, water, and even outside spaces. My son, as well as many other children with AS, sleeps in a specialized safety bed that keeps him enclosed and safe during the night.” Read more here: Why My Child’s Sleep Problems Just Can’t Be ‘Put to Bed’

  • Read more here:  Angelman syndrome children and adults have serious sleeping disorders

3.  Dysphagia and Gastrointestinal (GI) issues: 

     'Angelman Patients Frequently Have Gastrointestinal Problems': read more here

     GERD and Cyclic vomiting: Read more here: GERD and Cyclic vomiting (CVS)

     Reflux and constipation are common and can become serious if left untreated. Ideally GI issues should be treated                   holistically with an appropriate diet plan, correct positioning during and after meals, physical activity, as well as medical             intervention when necessary.  

     Dysphagia (swallowing problems): Some people with dysphagia have problems swallowing certain foods or liquids,               while others can't swallow at all.  Signs include coughing or choking when eating or drinking, bringing food back up,                   sometimes through the nose, a sensation that food is stuck in your throat or chest, persistent drooling of saliva 

     Over time, dysphagia can also cause symptoms such as weight loss and repeated chest infections.

     Eosinophilic Esophagitis (EE): Read more here - An Update on EE.

     Eosinophilic esophagitis is a chronic allergic inflammatory condition of the esophagus, characterized by symptoms such as       solid-food dysphagia (difficulty swallowing) and food impaction in adults, and feeding intolerance and GERD symptoms in         children. An EGD (Esophagogastroduodenoscopy) is a procedure that examines the esophagus, stomach and first portion         of the duodenum (small intestine) using a long flexible tube with a camera at the end of it. The scope is inserted into the             mouth and advanced to the small intestine.

     Constipation can be an ongoing issue and is best treated by adapting the diet, encouraging exercise, massage, and the

     intake of fluids. Medication should be used sparingly, only when really necessary.

     Elevated ammonia levels: Constipation and certain Epilepsy medications, eg. Epilim/Depakote (also known as valproic

     acid) can be causes of elevated ammonia levels, which can cause a variety of problems. Ammonia is a nitrogen waste               compound that is normally excreted in the urine. Elevated blood ammonia levels can affect a person at any age and

     happens for a variety of reasons. Read more here. 

4.   Anxiety and aggressive behaviours: 

      Watch on YouTube: Anxiety and Behavior Concerns with Christopher Keary, MD

      Read more on the Informational Series on Angelman Syndrome Behaviors.

      It is also important to access and model an appropriate communication system/device as early as possible to model 

      ‘self-  talk’ with AAC systems - as a tool necessary for self-regulating emotions. 

      Video modelling and the use of personal social stories on a tablet have also been known to help. 

      Current research study on: Anxiety in Angelman syndrome

      Behaviours that Challenge Associated with Frustration Related to Communication Difficulties

      Behaviours that Challenge Related to Anxiety

5.   Cyclic Vomiting: 

      Cyclic vomiting syndrome (CVS) can cause dehydration, injury to the food tube (sometimes the esophagus becomes so            irritated it bleeds), and tooth decay. The acid in vomit can corrode tooth enamel. If episodes occur more than once a                  month or require hospitalization, your doctor may recommend preventive medicine, such as amitriptyline, propranolol                (Inderal), cyproheptadine and topiramate.  Read more here.

      'Guidelines on management of cyclic vomiting syndrome in adults'

       'Treatment of Cyclic Vomiting Syndrome'

6.   Orthopedic conditions: 

      Scoliosis & Skeletal - see Management of Angelman Syndrome - A Clinical Guideline

      Gait and movement disorders: Physical therapy is essential to help improve ambulation. Sometimes bracing (AFOs) or          surgical intervention may be needed to properly align the ankles, feet and knees.

      OsteopeniaBone mineral density in Angelman syndrome

7.   Vision/Strabismus and CVI: 

      Angelman syndrome and Vision: read more here

      Management of strabismus requires evaluation by an ophthalmologist who will advise on a course of action. Read more

      on Cortical Visual Impairment Symptoms and Causes.

      Click on link here to watch a 2019 documentary about CVI, with explanations by Professor Gordon Dutton and Dr Cathy            Williams, Ophthalmologist from the CVI Project.

8.   Pica 

     The term pica originates in the Latin word for magpie (Picave), a bird that is famed for its unusual eating behaviors, where          it is known to eat almost anythingPica is the repeated or chronic ingestion of non-nutrient substances. In children with              developmental delay, pica occurs in 10–33%. Although many people with AS are picky eaters, they might still be impulsive        when it comes to chewing, biting and swallowing objects that are not food, eg. Foam stuffing, small objects, plastics, small        toys, gravel, balloons, etc.  This can cause choking and/or obstructions in the throat and digestive system that can become        serious and at times, lethal.

9.   Anesthetics and Surgery recovery: 

      Aspiration and respiratory distress: Though most people with AS are very resilient and seem to withstand anesthetics          and extensive surgeries well, many do struggle with recovery in the first few days after surgery. It is most important to                achieve good pain control while closely monitoring for aspiration and respiratory distress.

      Read more here: FAQs About Anesthesia in Angelman Syndrome

Despite the complex characteristics of this syndrome, there are many people who have Angelman syndrome who also enjoy a full life provided they have the right supports in place.


There are many people with AS, who:

...attend mainstream schools, are communicating and learning literacy & numeracy using AAC methods, enjoy taking their own photos and writing blogs (using technology), love eating out at restaurants, and regularly go out to the movies and attend live theatre productions. There are many sporty individuals with AS who love to be active. They may enjoy jumping on trampolines, riding bicycles, horse riding, swimming, snorkeling, snow skiing, ice skating, and even roller skating! And while some are able to participate actively in sports, those who are more physically affected by AS can get involved in other ways. Many participate in running events while being pushed in a buggy, or ride an adapted wheelchair bike, or support their team from the bench. See Emma’s story here.

The more adventurous individuals with AS (and their families) go camping and hiking in mountain ranges, and many love the thrill of surfing the waves, indoor skydiving, roller-coaster rides and tandem parasailing! Many also love to travel and see new places - by car, in a caravan/motor home, by plane, on sailing boats and even on cruise ships. One young lady with AS has even sailed across the world with her more adventurous family -

in their own sailing boat.

While most people with AS are very sociable, some may be more introverted or have anxieties around changing routines, going out, or being in unfamiliar places with strangers. However most are able to occupy themselves with technology (eg. watching YouTube videos) and enjoy their own hobbies such as cooking, board games, playing musical instruments, listening to music, making art, gardening and caring for animals.


Just like everyone else, people with AS have a wide range of abilities, talents and different areas of interest. They should all be respected as individuals and supported appropriately so that they can experience life to the fullest. 

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Key Recommendations
for Management

  • Diagnosis/Genetic counselling and testing. Specific gene sequencing tests are now available.

  • Access to a support association

  • Management plan for epilepsy – any type of seizure can occur. Recognition and management can be challenging

  • Management of hyperactive behaviour and disruptive sleep patterns if needed

  • Physiotherapy, occupational therapy and speech therapy

  • Respite and support for family

What does Angelman syndrome look like?​

  • What does Angelman Syndrome look like?:

      Short film by FAST (AU)