Which syndrome is the leading genetic cause of obesity?

• A. Prader-Willi syndrome
• B. Lesch-Nyhan syndrome
• C. Cerebral palsy
• D. Down syndrome

Answer: (A)

Prader-Willi syndrome is the leading genetic cause of obesity because it causes a lifelong, insatiable appetite due to hypothalamic dysfunction that disrupts appetite regulation, along with reduced energy expenditure. This hyperphagia typically appears in early childhood and, without careful management, leads to severe obesity. The genetic basis usually involves loss of paternal gene expression on chromosome 15q11-q13 (often from a paternal deletion or maternal uniparental disomy), with additional features such as hypotonia in infancy, developmental delays, short stature, and hypogonadism. While other conditions may involve obesity or related symptoms, they do not present with this distinctive pattern of hyperphagia and hypothalamic dysfunction, making Prader-Willi syndrome the best fit.