Prader-Willi syndrome: Genetics, clinical symptoms, and model systems

Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder caused by the absence of paternal gene expression within the PWS critical region (15q11-q13) on chromosome 15. The loss of gene function can result from deletion, maternal uniparental disomy, or imprinting center defects. Occurring equally in both sexes, PWS is characterized by a spectrum of physical, behavioral, and cognitive symptoms, including hyperphagia and obesity, and presents with various co-occurring psychiatric conditions such as autism spectrum disorder (ASD) and psychotic spectrum disorders (PSD). Approximately 12%–40% of individuals with PWS meet the criteria for ASD, while a smaller subset, around 10%–30%, may develop PSD in late adolescence or adulthood. The treatment of PWS typically involves a multidisciplinary approach, including behavioral interventions to manage hyperphagia, growth hormone therapy to address its deficiency, and pharmacological treatments for psychiatric symptoms. Additionally, there is growing interest in genetic and molecular therapies as potential future interventions. By integrating clinical, neurobiological, and genetic findings, this review highlights the implications of PWS for understanding co-occurring development, psychiatric disorders, and therapeutic potential through new intervention models.