About Angelman Syndrome

In 1965, Dr. Harry Angelman, an English physician, first described three children with characteristics now known as the Angelman syndrome (AS). He noted that all had a stiff, jerky gait, absent speech, excessive laughter and seizures. Other cases were eventually published but the condition was considered to be extremely rare and many physicians doubted its existence. The first reports from North America appeared in the early 1980s and within the last ten years many new reports have appeared. Dr. Angelman relates the following regarding his discovery of this syndrome.

"The history of medicine is full of interesting stories about the discovery of illnesses. The saga of Angelman's syndrome is one such story. It was purely by chance that nearly thirty years ago three handicapped children were admitted at various times to my children's ward in England. They had a variety of disabilities and although, at first sight, they seemed to be suffering from different conditions, I felt that there was a common cause for their illness. The diagnosis was purely a clinical one because, in spite of technical investigations which today are more refined, I was unable to establish scientific proof that the three children all had the same handicap. In view of this I hesitated to write about them in the medical journals. However, when on holiday in Italy I happened to see an oil painting in the Castelvecchio museum in Verona called . . . a Boy with a Puppet. The boy's laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman syndrome. This article was published in 1965, and after some initial interest, lay almost forgotten until the early eighties."

Angelman syndrome is usually not recognized at birth or in infancy since the developmental problems are nonspecific during this time. Parents may first suspect the diagnosis after reading about AS or meeting a child with the condition. The most common age of diagnosis is between three and seven years when the characteristic behaviors and features become most evident. A summary of the developmental and physical findings has recently been published for the purpose of establishing clinical criteria for the diagnosis and these are listed below. All of the features do not need to be present for the diagnosis to be made, and the diagnosis is often first suspected when the typical behaviors are recognized.

For several decades the chromosome study of AS individuals revealed no abnormalities, but with the development of improved methods a very small deleted area was found in chromosome 15. Molecular methods such as FISH (fluorescence in situ hybridization) now demonstrate a deletion in about 70% of individuals with AS. The deleted area, although extremely small, is actually quite large when viewed at the molecular level. It is believed to be about 4 million base pairs in length, enough to contain many genes.

The deleted region on chromosome 15 is known to contain genes that are activated or inactivated depending upon the chromosome's parent of origin (i.e., a gene may be turned on on the chromosome 15 inherited from the mother but off on the chromosome 15 inherited from the father). This parent-specific gene activation is referred to as genetic imprinting. Because the deletions seen in AS only occur on the chromosome 15 inherited from the mother, the gene(s) responsible for AS were predicted to be active only on the maternal chromosome 15. Disruption of genes that are active on the paternally-derived chromosome 15 is now known to cause another developmental disorder termed the Prader-Willi syndrome (PWS). The PWS gene(s) are actually located close to the AS gene, but they are different.

AS has been reported throughout the world among divergent racial groups. In North America, the great majority of known cases seem to be of Caucasian origin. Although the exact incidence of AS is unknown, an estimate of between 1 in 15,000 to 1 in 30,000 seems reasonable.