PraderWill

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of function of paternally expressed genes on chromosome 15q11-q13. In most cases this results from a deletion of the paternal 15q11-q13 region, but it can also arise from maternal uniparental disomy (two copies of chromosome 15 from the mother) or from an imprinting defect that prevents expression of paternal genes. PWS is characterized by hypotonia and poor feeding in infancy, followed by hyperphagia and obesity in later childhood, along with developmental and behavioral challenges.

Infancy typically presents with marked hypotonia, weak cry, feeding difficulties, and slow weight gain. After the first year, appetite increases dramatically and can lead to extreme obesity if not controlled. Other common features include short stature, small hands and feet, hypogonadism, learning difficulties, speech delay, and behavioral problems such as temper outbursts, rigidity, obsessive-compulsive traits, and skin picking. Sleep disturbances and sleep apnea are also common.

Diagnosis is achieved through genetic testing. DNA methylation analysis of the 15q11-q13 region detects the vast majority of cases, while additional testing with chromosomal microarray or sequencing can identify whether a paternal deletion, maternal uniparental disomy, or an imprinting defect is responsible.

Management requires a multidisciplinary approach. Growth hormone therapy is often used in children to improve height, body composition, and muscle tone. Dietary management, strict environmental controls, and structured meals are essential to mitigate hyperphagia and obesity. Physical, occupational, and speech therapies, educational support, and ongoing monitoring for endocrine issues, scoliosis, sleep disorders, and metabolic risks are part of routine care. Early diagnosis and coordinated care improve outcomes.

Prader-Willi syndrome was first described in the 1950s by Prader, Willi, and Laborde. Estimated prevalence is about 1 in 12,000 to 15,000 births, affecting all ages and both sexes.