Angelman syndrome

Angelman syndrome (AS) is an inherited disorder characterized by intellectual disability, speech impairment, seizures, and movement and balance problems. Babies affected with AS appear normal at birth. Around 6-12 months delays begin to be noticed in learning to walk or talk and a diagnosis can be made. Seizures typically begin around 2-3 years of age. Affected children usually have a very happy disposition. They can also be hyperactive and have difficulty sleeping. As they age, the hyperactivity and sleeping issues will sometimes improve. Life expectancy is normal, though independent living is not possible for adults with AS. There is no cure for AS. Pathogenic variants in the UBE3A gene is one of the causes of AS.

AS is inherited in a number of different complex ways, most of which are associated with a genetic phenomenon called genomic imprinting. Most genes in the body have two working copies, one inherited from mom and one inherited from dad. A small number of genes follow genomic imprinting inheritance wherein only one copy of the gene works and the other copy is essentially "turned off". This process is dependent upon which parent the gene was inherited from. Some imprinted genes are only turned on when inherited from mom and some imprinted genes are only turned on when inherited from dad. The UBE3A gene follows genomic imprinting inheritance; the copy inherited from mom is turned on and the copy inherited from dad is turned off. Pathogenic variants in the UBE3A can only cause AS when the child inherits the mutated copy from mom. If the dad had a pathogenic variant in UBE3A, it would be turned off and would not cause AS in any of the children who inherit his pathogenic variant. However, for the daughter who did inherit his pathogenic variant, she has a 1 in 2 chance of having a child affected with AS because her UBE3A copy would be turned on in her kids.

There are generally no signs or symptoms associated with being a carrier for AS. However, the risk to have a child affected with AS is increased.

AS affects between 1 in 12,000 and 1 in 20,000 newborns worldwide.

The following websites may be informative: Genetic Home Reference: Angelman syndrome (http://ghr.nlm.nih.gov/)

Gene Reviews: Angelman syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1116/) OMIM: [105830: ANGELMAN SYNDROME] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing