Prader–Willi syndrome shows why it matters which parent a gene came from
For a handful of genes on chromosome 15, only the copy inherited from the father does any work; the mother's is silenced. Lose the father's version and Prader–Willi syndrome follows: floppy, sleepy babies who grow into children with a hunger that no amount of food can satisfy.
The silencing process is called imprinting, and this condition, together with its mirror image, Angelman syndrome, were the first human disorders traced to it. In about 74% of cases part of the father's chromosome 15 has been deleted. In another 25% the child has two copies of the mother's chromosome and none from the father, so the imprinted genes stay switched off. When the mother's copy of a different gene in the same stretch is lost instead, the result is Angelman syndrome. Studies in people and mice point to the loss of 29 copies of a small RNA called SNORD116 as the main culprit.
The changes usually arise by chance as eggs or sperm form or in early development, rather than being inherited, and no risk factors are known. The chance of a brother or sister being affected depends on the mechanism: under 1% after a deletion, but up to 50% if the fault lies in the region that controls imprinting. The condition affects somewhere between 1 in 10,000 and 1 in 30,000 people, more than 400,000 worldwide, and a DNA methylation test picks up over 99% of cases. Because doctors see it rarely, it is sometimes mistaken for Down syndrome.
Infants typically have weak muscles, a feeble suck, a quiet cry and trouble waking. From childhood comes constant hunger, making it the most common genetic cause of severe obesity in children; families often put locks on refrigerators and cupboards. Researchers suspect disrupted signalling in the hypothalamus, including abnormal oxytocin-producing cells, plus high levels of the hunger hormone ghrelin. Short stature, small hands and feet, underdeveloped sex organs and mild learning difficulties are common.
Thinking skills are uneven. Many children read and handle visual tasks well and show a striking knack for jigsaw puzzles, though that may simply reflect practice, while arithmetic, short-term memory and processing of sounds lag. Between 70 and 90 percent develop stubbornness, tantrums or compulsive habits such as skin picking in early childhood. There is no cure, but in March 2025 US regulators approved a drug aimed at the intense hunger.
Source: Prader–Willi syndrome
