Angelman syndrome

If you are concerned that your child may have Angelman syndrome, it is important to speak to your child's doctor. Referral to a specialist, such as a geneticist, can be helpful to see whether your child's symptoms fit with a clinical diagnosis of Angelman syndrome (i.e. a diagnosis based on physical, health, and developmental features). If Angelman syndrome is a possibility, a geneticist or genetic counselor can recommend which type of genetic testing would be most appropriate for your child based on his or her symptoms. It is possible that more than one type of genetic test will be required before the genetic diagnosis can be made. These tests are usually performed on a blood sample obtained from your child and include:

• DNA methylation analysis - this test is used to see whether there is a problem with the imprinting of the UBE3A gene. Individuals who have a deletion of the maternal copy of UBE3A, two paternal copies of UBE3A, or an imprinting center defect will have an abnormal result (~80% of all individuals with Angelman syndrome). DNA methylation analysis does not detect the type of genetic problem present, so to additional testing is needed to identify the actual genetic change. A deletion of the maternally-inherited copy of UBE3A is the most common cause, and may be identified using fluorescence in situ hybridization (FISH), a PCR-based analysis or chromosomal microarray analysis. If no maternal deletion is identified, the next step is usually to test for paternal uniparental disomy (UPD). If paternal UPD is not detected, the cause is thought to be due to an imprinting defect.
• Sequence analysis of UBE3A - If the methylation analysis is normal, it is possible that there a genetic change affecting UBE3A. Based on your child's symptoms, the doctor may order a test just for UBE3A, or one that includes UBE3A as part of a panel of genes.
• To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.