Angelman Syndrome

Excerpt

In 1965 Harry Angelman, a British pediatrician, described the "Puppet Children," later being renamed Angelman syndrome (AS). Angelman described three children who had similar symptoms of learning disability, minimal or absent speech, ataxic and jerky movements, and a happy social disposition.

Angelman syndrome is a rare neurogenic disorder. It is a classic example of genomic imprinting, where the expression of a genomic region differs depending on the chromosome's parent of origin. AS is a neurodevelopmental disorder affecting mostly the nervous system that manifests with intellectual and developmental disabilities, a puppet-like ataxic movement and phenotype, as well as sleep disorders, and hyperactivity.

One of the causes of AS was found in 1987 through high-resolution chromosome banding technique, which revealed de novo microdeletions in the long arm of chromosome 15 in the region 11-13 (15q11-13). Later it was shown that there are multiple mechanisms other than deletions that can cause AS involving the region 15q11-13. We know now that the primary cause of Angelman syndrome is a selective loss of function of ubiquitin-ligase E3A(UBE3A) in the brain, which is usually expressed maternally.