PraderWili

Prader-Willi syndrome is a genetic imprinting disorder caused by loss of function of paternal genes on chromosome 15q11-q13. Most cases arise from a large deletion on the paternal chromosome, about a quarter from maternal uniparental disomy (two maternal copies), and a smaller percentage from imprinting defects. The condition is named after Andrea Prader and Heinrich Willi, who first described it in 1956. The disorder affects appetite regulation, growth, and development due to disrupted gene expression in the affected region.

Clinical features typically begin with severe hypotonia and feeding difficulties in infancy, followed by a period of poor growth and failure to thrive. In early childhood, individuals often develop hyperphagia and an insatiable appetite, which can lead to obesity if not tightly controlled. Other common features include short stature, hypogonadism, small hands and feet, and distinct facial characteristics. Intellectual impairment ranges from mild to moderate. Behavioral problems such as temper outbursts, anxiety, rigid routines, and skin picking are common. Sleep disturbances, including sleep apnea, are frequent, and orthopedic problems like scoliosis can occur.

Diagnosis is based on clinical suspicion confirmed by genetic testing. DNA methylation analysis of the 15q11-q13 region is diagnostic of Prader-Willi syndrome; additional tests (such as deletion analysis or single nucleotide polymorphism arrays) help determine the underlying mechanism (deletion, uniparental disomy, or imprinting defect) and guide genetic counseling.

Management requires a multidisciplinary approach. Early growth hormone therapy improves height, body composition, and muscle tone. Lifelong management focuses on strict dietary supervision to prevent obesity, regular physical activity, and treatment of hypogonadism when indicated. Supportive therapies (speech, occupational, and educational interventions) address developmental and behavioral needs. With comprehensive care, individuals with Prader-Willi syndrome can achieve a good quality of life, though obesity-related health risks remain a focus of ongoing care.