What Is Angelman Syndrome?
Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling, and usually a happy demeanor. People with AS are sometimes known as “angels”, both because of the syndrome’s name and because of their youthful, happy appearance. Dr. Harry Angelman, a pediatrician working in Warrington (then in Lancashire) first reported three children with this condition in 1965.
Angelman later described his choice of the title “Puppet Children” to describe these cases as being related to an oil painting he had seen while vacationing in Italy in Castelvecchio Museum in Verona called . . . a Boy with a Puppet. Individuals with AS require continuous care and are unable to live independently. They have a normal life expectancy. This is life today for people living with Angelman syndrome, but hope is here. Scientists believe that AS has the greatest potential for being cured when compared to other neurogenetic disorders and FAST (Foundation for Angelman Syndrome Therapeutics) has a plan well underway to achieve just that.
Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body’s tissues. In certain areas of the brain, however, only the copy inherited from a person’s mother (the maternal copy) is active. This parent-specific gene activation is caused by a phenomenon called genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.
Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.
In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent. This phenomenon is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.
The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the disorder in these cases. In some people who have Angelman syndrome, the loss of a gene called OCA2 is associated with light-colored hair and fair skin. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.