Which are the causes of Prader-Willi Syndrome?

Prader-Willi Syndrome (PWS) is a complex genetic disorder that affects various aspects of an individual's physical, cognitive, and behavioral development. It is caused by the absence or abnormal expression of certain genes on chromosome 15. PWS is typically characterized by hypotonia (low muscle tone) in infancy, followed by hyperphagia (excessive appetite) and obesity in childhood.

The causes of Prader-Willi Syndrome can be attributed to several factors:

1. Genetic Deletion: The most common cause of PWS is a deletion of a specific region on the paternal chromosome 15. This deletion occurs in approximately 70% of individuals with PWS. The deleted region contains several genes, including the SNRPN (small nuclear ribonucleoprotein polypeptide N) gene, which is believed to play a crucial role in the development of PWS.



2. Uniparental Disomy: In about 25% of PWS cases, there is a phenomenon called uniparental disomy (UPD). UPD occurs when an individual inherits both copies of chromosome 15 from one parent, instead of one copy from each parent. In PWS, this usually involves inheriting two copies of the maternal chromosome 15, while the paternal chromosome 15 is completely missing. This results in the absence of the necessary genetic material from the paternal chromosome, leading to the development of PWS.



3. Imprinting Defects: Imprinting is a process that regulates gene expression based on the parent of origin. In a small percentage of PWS cases (around 1-3%), there are imprinting defects that disrupt the normal expression of genes on chromosome 15. These defects can occur on either the maternal or paternal chromosome, leading to the development of PWS.



4. Rare Genetic Mutations: In a very small number of PWS cases, rare genetic mutations may be responsible for the syndrome. These mutations can affect the expression or function of genes involved in the development of PWS. However, such mutations are relatively uncommon and account for a minority of PWS cases.

It is important to note that Prader-Willi Syndrome is not caused by any actions or choices made by the parents or affected individuals. It is a genetic condition that occurs randomly and is not related to any environmental factors or lifestyle choices.

Understanding the causes of PWS is crucial for accurate diagnosis, genetic counseling, and potential future treatments. Ongoing research aims to further unravel the complex genetic mechanisms underlying PWS, which may lead to improved interventions and therapies for individuals with this syndrome.