Angelman Syndrome Health Article

Definition

Angelman syndrome (AS) is a genetic condition that causes severe mental retardation, severe speech impairment, and a characteristic happy and excitable demeanor.

Description

Individuals with AS show evidence of delayed development by 6–12 months of age. Eventually, this delay is recognized as severe mental retardation. Unlike some genetic conditions causing severe mental retardation, AS is not associated with developmental regression (loss of previously attained developmental milestones).

Severe speech impairment is a striking feature of AS. Speech is almost always limited to a few words or no words at all. However, receptive language skills (listening to and understanding the speech of others) and non-verbal communication are not as severely affected.

Individuals with AS have a balance disorder, causing unstable and jerky movements. This typically includes gait ataxia (a slow, unbalanced way of walking) and tremulous movements of the limbs.

AS is also associated with a unique "happy" behavior, which may be the best-known feature of the condition. This may include frequent laughter or smiling, often with no apparent stimulus. Children with AS often appear happy, excited, and active. They may also sometimes flap their hands repeatedly. Generally, they have a short attention span. These characteristic behaviors led to the original name of this condition, the "Happy Puppet" syndrome. However, this name is no longer used as it is considered insensitive to AS individuals and their families.

Genetic profile

The genetics of AS are complex. There are at least five different genetic abnormalities that can cause the condition, all of which involve a specific region of the chromosome 15 inherited from the mother. This region is designated 15q11-13 (bands 11 through 13 on the long arm of chromosome 15). The fact that AS occurs only when there are abnormalities in this region of the maternal copy of chromosome 15 reflects a unique phenomenon known as imprinting. Imprinting is a chemical modification of DNA which acts as an "identification tag" indicating which parent contributed the chromosome. Imprinted genes or chromosome regions are expressed or not expressed depending on which parent transmitted the chromosome. Abnormalities in the paternally (from the father) inherited 15q11-13 region cause a different genetic condition called Prader-Willi syndrome.

Chromosome deletion

The most common cause of AS is a small deletion (missing piece) in the maternally inherited chromosome 15. Specifically, the deletion occurs within 15q11-13. Approximately 70% of AS individuals have this deletion.