Angelman syndrome (AS) is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements especially hand-flapping, frequent laughter or smiling, and usually a happy demeanour. AS is a classic example of genetic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15.
What causes it?
Angelman syndrome is a chromosomal disorder caused by the absence of a gene. Interestingly, 75 per cent of those with Angelman syndrome have a similar genetic fault to that found in another genetic condition, Prader-Willi syndrome, but occurring on the chromosome 15 inherited from the mother rather than the father.
The genetic abnormality may be due to one of several possible types of problems with the chromosomes:
A small deletion of part of chromosome 15 - this accounts for about 75 per cent of cases
Paternal disomy - about two to three per cent of cases result from inheriting two copies of chromosome 15 from the father
Mutation of the UBE3A gene in 15 per cent - there's a risk the condition will recur in other children born to the mother
Translocation involving chromosome 15 in a few cases
An error in the imprinting of chromosome 15 in about five per cent
In some cases, the genetic abnormality has yet to be identified
Chromosome 15 is almost unique in that it carries an imprinted region, which means that it's marked so the copy inherited from the mother behaves differently from that from the father. Errors in imprinting can affect a baby's development. In this type of Angelman syndrome, there's a risk the condition will recur in other children born to the mother.
What are the symptoms?
Typical features of Angelman syndrome are a small head (microcephaly), epilepsy, severe learning difficulties (with poor communication skills and little or absent speech), an unsteady or ataxic gait, a characteristic facial appearance and a happy disposition.
How is it diagnosed?
Early developmental delay may be noticed but the diagnosis isn't usually made until the age of three or later, when other features become apparent.
Genetic tests can confirm the diagnosis. These may be done antenatally using CVS or amniocentesis if there's known to be a risk. However, in most cases the condition does not recur within one family.
What's the treatment?
There's no cure for Angelman syndrome. Support for specific problems such as learning difficulties is important.