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About Angelman Syndrome

Testing & Diagnosis

Genetic testing for Angelman syndrome can be complicated! Angelman syndrome is always caused by a lack of functional UBE3A protein in the brain. But because there are different genetic causes, also called genotypes, there are multiple different methods to test for AS. This page is a quick summary of the typical testing methods.

The available tests for AS have changed over time, as understanding of AS and genetic testing methods have improved.  Please note that the best test for an individual can vary depending on the characteristics of that person and that not all tests are available in all places.   

Evolution of Genetic Testing

DNA Methylation Test

MS-MLPA

UBE3A Sequencing

Chromosomal Microarray (CMA, CGH, or microarray)

FISH

ICD Deletion Testing

UPD15

Standard Chromosome Analysis (karyotype)

Whole Exome or Whole Genome Sequencing (WES or WGS)

Testing Table

As you can see from the table above, there is not currently one test that can diagnose or rule out all AS genotypes.  New technologies that CAN diagnose all AS genotypes in just one test are currently being studied in some research laboratories.  One example is called long-read sequencing or nanopore long-read sequencing.  Having just one clear and accurate test would help health care providers and most importantly families get to a diagnosis quickly and with much less confusion!  

What if all the genetic testing is negative? 

Past data showed that up to 10% of individuals who have all of the key characteristics of AS had negative genetic testing for AS, meaning that methylation studies and sequencing of the UBE3A gene do not show any causes of AS. There are other conditions that have many of the same symptoms or features as AS, so it is important that the individual is also tested for these disorders as well.  If an individual has negative genetic testing for AS and for the other conditions that can look very similar AND a clinician familiar with AS makes the diagnosis, the person may be said to have a “clinical diagnosis” of AS. It is possible that some individuals with a clinical diagnosis may have a genetic variant in UBE3A or genomic imprinting that current genetic testing methods are not able to identify, or that they may have a different genetic condition that has very similar characteristics.   

A geneticist or genetic counselor can review the genetic testing that has been done thus far, to help you determine if additional genetic testing may be indicated. 

Click here to schedule with FAST’s genetic counselor if that would be helpful for you.   

Updated as of July 2024

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