A painting in Verona gave Angelman syndrome its first name
In the mid-1960s an English paediatrician suspected three children on his ward shared one condition but could not prove it. On holiday in Italy he saw a painting of a laughing boy holding a puppet, and it prompted the paper he called Puppet Children. The disorder now bears his name: Angelman syndrome.
Harry Angelman worked in Warrington and published his three cases in 1965. The children had different disabilities, but he sensed a common cause in their jerky movements and cheerful faces. His diagnosis was purely clinical, which is why he hesitated before writing it up, and not every parent liked his label. The article drew brief attention and then lay largely forgotten until the early 1980s, when American doctors including Charles Williams and Jaime Frias began reporting cases of what was then called happy puppet syndrome.
Genetics then filled in the picture. In 1987 physician Ellen Magenis found that about half of affected children lack a small piece of chromosome 15, and in 1997 Arthur Beaudet traced the cause to a gene called UBE3A. The mechanism is unusual. Each child inherits a copy from both parents, but in parts of the developing brain the father's copy is switched off by a process called imprinting. The brain therefore depends entirely on the mother's copy, and when that copy is missing or faulty, development suffers.
There are several ways to lose it. In roughly 70 percent of cases the maternal stretch of chromosome is deleted; in about 11 percent the gene carries a mutation; around 6 percent involve a defect in the region that controls imprinting; and about 3 percent arise because a child inherited two paternal copies and none from the mother. The genetic route predicts severity, with deletions tending to cause the most serious symptoms.
Every diagnosed person shows severe developmental delay, little or no speech, movement or balance problems, and a strikingly happy, excitable manner with frequent laughter. Most also have a small head and seizures beginning before age three. Estimates suggest it affects around 1 in 15,000 people, and males and females equally.
Source: Angelman syndrome
