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Testing For Angelman Syndrome

Getting an Accurate Diagnoses

Genetic Health Service NZ provides genetic diagnostic and genetic counselling services, operating fourteen clinics throughout the country. They also provide assistance in managing genetic conditions, expert advice on genetic diseases and education on genetics.




How to test for Angelman Syndrome

AS diagnosis requires taking a blood sample from your child for genetic studies and it determines parental DNA pattern, missing chromosomes, and gene mutation. Parental DNA pattern, known as a DNA methylation test, screens for three out of four mechanisms that cause the syndrome. A fluorescence in situ hybridization test or a comparative genomic hybridization test can determine missing chromosomes. Sometimes, Angelman may occur when a person's maternal copy of the UBE3A gene is active, but mutated and that decides whether or not the child has the syndrome.

A breakdown of the main AS genotypes

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).

  1. Deletion +, or 15q11.2-q13 deletions (68% of cases) – the majority of AS cases are caused by deletions on the maternal copy of Chromosome 15. Due to genomic imprinting, only the maternal copy of UBE3A is expressed in the brain. The deletion removes the normal expression of this gene in AS individuals.

  2. UBE3A mutations (11% of cases) – In these individuals, 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) – in UPD, the individual has two copies of paternal Chromosome 15. Because UBE3A is not expressed from the paternal copy, these individuals lack normal levels of UBE3A in the brain.

  4. Imprinting defect (3% of cases) – These individuals may have a deletion of the imprinting center an Chromosome 15, but could also be caused by loss of imprinting information during the mother’s oogenesis. Loss of imprinting will prevent expression of the maternal UBE3A gene in the brain.

  5. Clinical/other (11%) – In these individuals, all testing for Angelman Syndrome is normal, 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.


Whole Exome Sequencing

Further testing: The purpose of whole exome sequencing is to find a genetic cause of your/your child’s symptoms. Most people who have WES have already had some genetic testing. WES is one of the most extensive genetic tests available. Because WES looks at more genes than most genetic tests, it may find a genetic cause, even if previous genetic testing did not. Read more on Whole Exome Sequencing

Prenatal Genetic Diagnosis for Angelman Syndrome: Read more here


Similar disorders / Differential diagnosis

While AS can initially be misdiagnosed as Autism or Cerebral Palsy (CP), there are many other conditions that may mimic AS. Read more here: Angelman syndrome: Mimicking conditions and phenotypes (Williams CA, Lossie A, Driscoll D, R.C. Phillips Unit)

List of conditions similar to AS:

  • Pitt Hopkins syndrome: Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features. People with Pitt-Hopkins syndrome typically do not develop speech; some may learn to say a few words. Many affected individuals exhibit features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills.

Facebook support groups



FB groups for rarer genotypes of AS

       If your child has similar traits to AS but all tests come         back negative, they may be given the Clinical/other             diagnoses.


Misdiagnosis Matters

Clinical research: Angelman gene variants alter symptoms:

‘About 10% of people diagnosed with Angelman syndrome do not have a clear genetic cause, even with the availability of advanced genomic technologies. A study published 29 January in the American Journal of Medical Genetics encourages clinicians to consider similar disorders, which all present with speech difficulties and delays, when diagnosing these children’. One of the first large-scale, ongoing studies documenting the symptoms of Angelman syndrome — a neurological disorder with features similar to autism — is calling into question some of the so-called characteristic symptoms of the syndrome. 


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