Angelman syndrome (AS) is a genetic condition that affects the nervous system (neurogenetic condition).^1,2 Symptoms and complications may vary between individuals with AS. In childhood, AS is often characterised by, but not limited to, developmental delay, intellectual disability, speech impairment, impaired movement and balance (ataxia), small head size (microcephaly) and seizures.^1-4 Individuals with AS tend to present with a happy demeanour, including frequent smiling, laughter, excitability and hand-flapping movements. These symptoms typically present after 1 year of age, although developmental delay may be observed prior.^3,4

AS is caused by the absence of a functional UBE3A gene.¹ There are several different genetic mechanisms that may result in the loss of the UBE3A gene function, with some observations of a phenotype-genotype correlation, in which the presentation of some symptoms (phenotypes) may be influenced by the individual’s genetic defect (genotype).^3,4

AS is not a degenerative condition but there may be other symptoms and complications that present during adulthood and individuals with AS will require life-long care.

There are no known synonyms.

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:72 Angelman syndrome

ICD-11: LD90.0 Angelman syndrome

Common features of Angelman Syndrome (AS) in childhood include development delay, usually presenting between 6 months and 2 years of age, with other clinical presentations often observed after 1 year of age, such as severe intellectual disability, speech impairment, issues with movement and balance (ataxia), small head size (microcephaly) and seizures.^1-4 Other complications may include feeding difficulties in babies, sleep disturbances, increased sensitivity to heat and sideways curvature of the spine (scoliosis).^2-4 There are also distinct behavioural traits, such as a happy demeanour consisting of frequent laughing, smiling, excitability and hand-flapping movements, as well as a tendency to be fascinated with water.

Adults with AS may have severe intellectual disability and speech impairment, requiring the use of Augmentative and Alternative Communication (AAC) tools.⁵ They may also have issues related with behaviour, anxiety, sleep, gastrointestinal health issues such as gastroesophageal reflux disease (GERD) and constipation, dental care, vision, obesity, scoliosis, bone density and mobility.

Another common feature in Angelman adolescents and young adults are movement disorders, including nonepileptic myoclonus (NEM), which is characterised by sudden, involuntary jerking of a muscle or group of muscles.⁶ NEM episodes could last seconds to hours, typically starting in the hands and may spread to the face and extremities. Although it does not affect consciousness or cause cognitive consequences, NEM can affect the quality of life significantly and treatment is difficult.⁶ This is distinct from the AS epileptic seizures that often start in childhood but can persist to and through adulthood, with some incidence of seizures improving in late childhood and then recurring or worsening in adulthood.^5,7

Symptoms and complications may vary between individuals with AS. Please speak to your medical team to learn more about the symptoms and complications of AS.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Angelman Syndrome (AS) is caused by the loss of function of the maternal UBE3A gene on Chromosome 15.³ All individuals have two copies of Chromosome 15 (a maternal copy from their mother and a paternal copy from their father). The paternal UBE3A gene is normally silenced (not expressed) due to a phenomenon called genomic imprinting and only the maternal UBE3A copy is active and responsible for normal function. Loss of maternal UBE3A expression results in AS.

Loss of maternal UBE3A expression can be caused by different genetic defects, with the most common being a deletion of the Chromosome 15q11.2-q13 critical region where the UBE3A gene is located. AS can also be caused by mutations in the UBE3A gene, uniparental disomy (inheritance of two paternal chromosome 15 and no maternal chromosome 15), imprinting defects (interfering with the normal genomic imprinting pattern) and structural rearrangements of chromosome 15.³ Most of these genetic defects causing AS are random occurrences and not inherited, but there are cases where the genetic cause is inherited from a parent.^1,3

In some cases, individuals have been clinically diagnosed with AS based on their symptoms but no genetic changes have been detected through genetic testing. However, there may be other genetic defects affecting UBE3A expression that are yet to be identified.³

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of Angelman Syndrome (AS) may be made through clinical examination of symptoms and/or molecular genetic testing.^1,2

Consensus criteria for clinical diagnosis of AS have been developed in the United States (US) together with the Scientific Advisory Committee of the US Angelman Syndrome Foundation.⁴ A list of these criteria can be found at

• GeneReviews®: Angelman Syndrome – Clinical criteria that help establish the diagnosis
• Clinical and genetic aspects of Angelman syndrome (2010 review)

An available genetic test for AS in Australia is genome-wide chromosome microarray testing, using a blood sample, to detect deletions on Chromosome 15 in the first instance. General information about genome-wide microarray tests can be found at Pathology Tests Explained: Genome-wide chromosome microarray testing. If no deletion is detected, this does not necessarily rule out an AS diagnosis – further genetic testing can be performed to identify if other genetic defects associated with AS are present.

There may be cases where genetic changes in the UBE3A gene may not be detected by current molecular diagnostic methods and a diagnosis of AS may be made based on clinical presentation; however, differential diagnosis should be carried out to rule out other conditions in those situations.³ Conditions that can be considered in the differential diagnoses may include, but are not limited to, autism spectrum Level 3 (non-verbal), cerebal palsy (Level III-IV), Pitt Hopkins syndrome and Christianson syndrome. More information about conditions to be considered in the differential diagnosis can be found at GeneReviews®: Angelman Syndrome – Differential Diagnosis.

Please speak to your medical team to learn more about the available diagnostic pathways for AS.

There is currently no curative treatment for AS. Treatment is targeted at managing symptoms, involves a multidisciplinary care team and could include lifelong care. Management strategies may consist of physiotherapy, occupational therapy, speech therapy, special education as well as social skills and communication training.² Anti-epileptic medication may sometimes used to control seizures. Monitoring of visual function should also be considered.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the management of Angelman Syndrome (AS) may include general practitioners (GP), paediatricians, geneticists, psychiatrists, neurologists, ENT specialists, respiratory/sleep specialists, orthopaedic and spinal specialists, speech therapists, physiotherapists, orthotists, dieticians, occupational therapists and clinical nurses. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome has been developed by an international team of specialists that manage patients with Angelman Syndrome (AS); this includes input from an Australian-based specialist. This collaborative project documents the common issues that accompany AS and the most common and established ways of providing care for those issues.

OrphanAnesthesia has Anaesthesia recommendations for Angelman Syndrome; please note this was last updated in 2019.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

Below are some considerations for the emergency management of individuals living with Angelman Syndrome, including when presenting to emergency departments:¹

• will need 24/7 attendant/carer support in Emergency and Hospital, regardless of age
• predominantly non-verbal and may use Alternative and Augmentative Communication tools and devices; will require a familiar communication partner
• will have stronger receptive communication skills (ability to understand information) than expressive communication skills (ability to produce language)
  *Healthcare professionals – please presume competence and explain in simple terms what is happening, to manage anxiety*
• may have a high pain threshold
• may be prone to seizures if unwell
• may present with laughing as part of their pain signature or in response to anxiety
• may have challenging behaviours if distressed

The Global Angelman Syndrome Registry collects and houses data of individuals diagnosed with Angelman Syndrome (AS), which can be used to advance learning and research as well as to support clinical trial design and patient recruitment.

Research on the healthcare and parental productivity costs of raising a child with AS in Australia:

• Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years
• The Cost of Raising Individuals with Fragile X or Chromosome 15 Imprinting Disorders in Australia

For information on other research on AS, please visit FAST Australia: Research.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

Australian Organisations:

In Australia, there are two organisations working collaboratively to support the Angelman community. Angelman Syndrome Association Australia (ASAA) provides support for all day-to-day aspects of living with AS, whilst FAST Australia is focused on funding AS research and initiatives that lead to new treatments and excellence in clinical care.

 Angelman Syndrome Association Australia (ASAA)
Website: https://angelmansyndrome.org/

Foundation For Angelman Syndrome Therapeutics (FAST) Australia
Website: https://cureangelman.org.au/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Angelman Syndrome (AS) varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

Angelman Syndrome Association Australia provides for families experiencing emergencies/crises through the Angelman Syndrome Family Support Fund.¹

Information on the National Disability Insurance Scheme (NDIS) relevant to Angelman Syndrome (AS) can be found at:

• Angelman Syndrome Association Australia: The NDIS – Information & Resources
• Angelman Syndrome Association Australia: NDIS guide for Angelman Syndrome

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on AS can be found at:

• healthdirect: Angelman syndrome
• Raising Children Network: Angelman syndrome in children
• Genetic and Rare Diseases (GARD) Information Center: Angelman Syndrome
• National Organization for Rare Disorders (NORD): Angelman Syndrome

Gene Reviews: Angelman Syndrome

Online Mendelian Inheritance in Man, OMIM^® #105830 – Angelman Syndrome; AS

Orphanet: Angelman Syndrome

Human Phenotype Ontology (HPO): Angelman Syndrome

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Angelman Syndrome Association Australia and Foundation For Angelman Syndrome Therapeutics (FAST) Australia.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.