Angelman Syndrome (AS)

Developmental Anomalies

Angelman Syndrome (AS)

IMPORTANT INFORMATION

The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.

Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.

RVA Partner(s)

Angelman Syndrome Association Australia (ASAA)
Foundation For Angelman Syndrome Therapeutics (FAST) Australia

For more information on this disease, please refer to Angelman Syndrome Association Australia1 and Foundation For Angelman Syndrome Therapeutics (FAST) Australia.2

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 misleading information, please let us know via the Contribute page.

Contributors

This page has been co-developed with RVA Partners, Angelman Syndrome Association Australia1 and Foundation For Angelman Syndrome Therapeutics (FAST) Australia.2

Emergency Management

Below are some considerations for the emergency management of individuals living with Angelman Syndrome, including when presenting to emergency departments1:

  • 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
Clinical Care Guidelines

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.

Synonyms

ORPHA:72

ICD-11 LD90.0 Angelman syndrome

Summary

Angelman Syndrome (AS) is a genetic condition caused by the absence of a functional UBE3A gene.1-3 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).4,5

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.1-6 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.4,5 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.1,2

Symptoms

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, including severe intellectual disability, speech impairment, issues with movement and balance (ataxia), small head size (microcephaly) and seizures.1-6 Other complications may include feeding difficulties in babies, sleep disturbances, increased sensitivity to heat and sideways curvature of the spine (scoliosis).1,4-6 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.2,4-6

Adults with AS may have severe intellectual disability and speech impairment, requiring the use of Augmentative and Alternative Communication (AAC) tools.7 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. 7

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.1,8 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.8 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.7,9

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.

Cause/Inheritance

Angelman Syndrome (AS) is caused by the loss of function of the maternal UBE3A gene on Chromosome 15.1,2 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. Defects resulting in 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 15.1,2,4 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.3,4

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.2,4

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 on genetic counselling can be found on the National Services page and specific State and Territory Services pages on the RARE Portal.

Diagnosis

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 AS5 have been developed in the United States (US) together with the Scientific Advisory Committee of the US Angelman Syndrome Foundation. A list of these criteria can be found at GeneReviews®: Angelman Syndrome – Clinical criteria that help establish the diagnosis4 as well as within a 2010 review: Clinical and genetic aspects of Angelman syndrome.

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.1,2 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.2

General information about Genome-wide Microarray tests can be found at Pathology Tests Explained: Genome-wide chromosome microarray testing.

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.2,4 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.1

Treatment

Whilst there is no overall curative treatment for Angelman Syndrome (AS), there are available therapies for managing symptoms. This may involve a multidisciplinary team and could include lifelong care. Management strategies may consist of physical, occupational and speech therapy, special education as well as social skills and communication training.1,6 Anti-epileptic medication are sometimes used to control seizures. Monitoring of visual function should also be considered.6

It is best to speak with your medical team to learn more about suitable management therapies.

Clinical Care

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.1,2,3 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Research

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:

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

Please visit Australian Clinical Trials to learn more about clinical trials for AS in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for AS in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

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

Rare Disease Organisation(s)

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) RVA Partner Australian Organisation
Website: https://angelmansyndrome.org/
Address: Angelman Syndrome Association Australia Inc
PO Box 554
Sutherland NSW 1499
Contact form: https://angelmansyndrome.org/contact

Foundation For Angelman Syndrome Therapeutics (FAST) Australia RVA Partner Australian Organisation
Website: https://cureangelman.org.au/
Phone: 1300 078108
Email: info@cureangelman.org.au
Address: PO Box 689
Bungalow Qld 4870
Contact form: https://cureangelman.org.au/contact/

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

Social Services

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:

Please visit the National and State Services pages for general social services.

Mental Health

Please visit the ‘Mental Health’ sections listed on the National and State Services pages.

Other

Further information on Angelman Syndrome (AS) can be found at:

References
  1. Angelman Syndrome Association Australia [Internet]. 2020. Available from: https://angelmansyndrome.org/
  2. Foundation For Angelman Syndrome Therapeutics (FAST) Australia [Internet]. 2023. Available from: https://cureangelman.org.au/
  3. Genetic and Rare Diseases (GARD) Information Center. Angelman Syndrome. Accessed 2 Feb 2023. https://rarediseases.info.nih.gov/diseases/5810/angelman-syndrome/
  4. GeneReviews® – Angelman Syndrome [Internet]. 1998. [updated 2021 April 22]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1144/
  5. Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA et al. Angelman syndrome 2005: Updated consensus for diagnostic criteria. Am. J. Med. Genet. A. [Internet]. 2006;140(5):413-8. Available from: https://doi.org/10.1002/ajmg.a.31074
  6. Orphanet. Angelman Syndrome. Accessed 2 Feb 2023. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=72
  7. Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL. Angelman Syndrome in Adulthood. Am. J. Med. Genet. A. [Internet]. 2015; 167A(2): 331-344. Available from: https://doi.org/10.1002/ajmg.a.36864
  8. Pollack SF, Grocott OR, Parkin KA, Larson AM, Thibert RL. Myoclonus in Angelman Syndrome. Epilepsy & Behavior [Internet]. 2018; 82:170-174. Available from: https://doi.org/10.1016/j.yebeh.2018.02.006
  9. Duis J, Nespeca M, Summers J, Bird L, Bindels-de Heus KGCB, Valstar MJ et al. A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome. Mol. Genet. Genomic Med. [Internet]. 2022; 10(3): e1843. Available from: https://doi.org/10.1002/mgg3.1843
Page Last Updated

12/09/2023 15:10