Prader-Willi Syndrome: Osmosis Study Video

Summary

Prader-Willi Syndrome is a genetic disorder caused by mutations on the paternal chromosome 15, leading to a variety of physical and developmental challenges. In infancy, symptoms include poor feeding and low muscle tone, while childhood brings overeating, intellectual disability, and low sex hormone levels. Characteristic features include almond-shaped eyes, a narrow forehead, and small hands and feet. Genetic testing confirms diagnosis, and management focuses on food restriction and growth hormone therapy. While there is no cure for overeating, the condition is linked to imprinting and can be differentiated from Angelman Syndrome, which occurs with maternal mutations.

Takeaways

• 😀 Prader-Willi Syndrome (PWS) is a genetic disorder caused by mutations in the paternal copy of chromosome 15.
• 😀 Infants with PWS experience low muscle tone and poor feeding, while children develop overeating, intellectual disability, and low sex hormones.
• 😀 The condition is caused by the failure of certain genes to be expressed due to genetic imprinting, where only the paternal genes are active.
• 😀 Epigenetic processes, such as DNA methylation, play a key role in turning off the maternal genes, leading to PWS.
• 😀 The most common genetic causes of PWS include paternal gene deletions, maternal uniparental disomy, mutations in the imprinting center, and chromosomal translocations.
• 😀 Children with PWS have distinct physical features, including almond-shaped eyes, a narrow forehead, and small hands and feet.
• 😀 Symptoms of PWS include developmental delay, low IQ, short stature, and obesity caused by dysfunction in the hypothalamus that leads to constant hunger.
• 😀 PWS patients often have difficulty regulating food intake, which can lead to morbid obesity, type 2 diabetes, and obstructive sleep apnea.
• 😀 Diagnosis of PWS is confirmed through genetic testing, which identifies the specific mutations or genetic abnormalities responsible.
• 😀 Current treatment focuses on food restriction and the use of growth hormones to improve height and body composition, but there is no effective treatment for controlling overeating.

Q & A

What is Prader-Willi Syndrome?

Prader-Willi Syndrome (PWS) is a genetic disorder caused by mutations or deletions in the paternal copy of genes on chromosome 15, leading to developmental and physical abnormalities, including low muscle tone, poor feeding in infancy, overeating, obesity, intellectual disability, and hormone deficiencies.

How does imprinting contribute to Prader-Willi Syndrome?

Imprinting is a genetic process where only one copy of a gene is expressed, usually the paternal copy. In Prader-Willi Syndrome, the paternal copy of genes on chromosome 15 is either deleted or mutated, and the maternal copy is imprinted (silenced), leading to a lack of gene expression.

What role does DNA methylation play in the development of Prader-Willi Syndrome?

DNA methylation is an epigenetic process that silences genes. In Prader-Willi Syndrome, the methylation of the maternal copy of the genes on chromosome 15 prevents its expression, while the paternal copy is either deleted or mutated, leading to a lack of functional gene products.

What are the most common causes of Prader-Willi Syndrome?

The most common causes of Prader-Willi Syndrome include a deletion of the paternal genes on chromosome 15, maternal uniparental disomy (both copies of chromosome 15 from the mother), mutations in the imprinting center, and epimutations that prevent the erasure of methylation marks.

How do maternal uniparental disomy and trisomy 15 relate to Prader-Willi Syndrome?

Maternal uniparental disomy occurs when both copies of chromosome 15 are inherited from the mother, leading to silencing of all genes in the Prader-Willi region. Trisomy 15, which involves three copies of chromosome 15, is incompatible with life, and when a fetus loses one chromosome during early development (trisomy rescue), it may result in Prader-Willi Syndrome if the paternal chromosome is lost.

What is the function of the imprinting center in relation to Prader-Willi Syndrome?

The imprinting center is a region of DNA that directs the silencing of the maternal copy of genes on chromosome 15. If the imprinting center itself is mutated, it can result in silencing of both the maternal and paternal copies of the genes, leading to Prader-Willi Syndrome.

What are the typical physical features of individuals with Prader-Willi Syndrome?

Individuals with Prader-Willi Syndrome often have distinct physical features, including almond-shaped eyes, a narrow forehead, a thin upper lip, small hands and feet, and low muscle tone.

How does Prader-Willi Syndrome affect hormone levels and growth?

Prader-Willi Syndrome can lead to deficiencies in hormones such as gonadotropin-releasing hormone (GnRH) and growth hormone, resulting in delayed puberty, inadequate genital development, and short stature.

Why do individuals with Prader-Willi Syndrome tend to overeat?

Overeating in Prader-Willi Syndrome is caused by dysfunction in the hypothalamus, which is responsible for regulating hunger. This dysfunction results in abnormal hunger signals, leading individuals to feel hungry even when their stomach is full.

What are the current approaches to managing Prader-Willi Syndrome?

Management of Prader-Willi Syndrome typically involves strict food monitoring to prevent overeating and obesity, often by locking away food. Growth hormone therapy may be used to improve height and lean body mass, but there is currently no medication or surgery to control overeating.