- intellectual and developmental delay
- sleep disturbance
- jerky movements (especially hand-flapping)
- frequent laughter or smiling
- and usually a happy demeanor.
AS is a classic example of genomic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced. The sister syndrome, Prader-Willi syndrome, is caused by a similar loss of paternally inherited genes and maternal imprinting.
AS is named after a British pediatrician, Dr. Harry Angelman, who first described the syndrome in 1965. An older, alternative term for AS, happy puppet syndrome, is generally considered pejorative and stigmatizing so it is no longer the accepted term, though it is sometimes still used as an informal term of diagnosis.
What is the cause and is testing available?
Angelman syndrome is caused by a defective gene on the maternally derived chromosome 15q11.2 region. The syndrome occurs with equal frequency in males and females. Approximately 70% of individuals with Angelman syndrome have a chromosome deletion (detected by fluorescence in situ hybridization or F.I.S.H.). Less than 5% have inherited both chromosome 15s from their father (uniparental inheritance) instead of one chromosome 15 from each parent; less than
5% have an imprinting defect in 15q11.2; and 10 to 15% have a small DNA alternation (or mutation) in the Angelman Syndrome Gene or UBE3A. In the remaining AS individuals (approximately 10%), the cause cannot yet be determined by laboratory testing and the diagnosis is based on clinical features. Depending on the cause of AS, families may have from less than 1% (i.e. that of the general population) up to a 50% chance of having another child with AS. Laboratory testing for AS is available at most major medical genetic clinics. Testing often includes a combination of chromosomal and