Prader Willi syndrome: advances in genetics.

Abstract

Prader-Willi syndrome (PWS) is a complex genetic disorder arising from abnormalities on chromosome 15q11.2-q13, characterized by distinct physical, cognitive, and behavioral features that evolve across the lifespan. Early manifestations include severe hypotonia, feeding difficulties, and failure to thrive in infancy, progressing to hyperphagia, obesity, intellectual disabilities, and behavioral challenges in later stages. Additional features include growth hormone deficiency, short stature, delayed puberty, and other endocrine abnormalities. Genetic advances have illuminated the role of imprinted genes, such as SNORD116, in driving the syndrome's core features, offering insights into its variability and severity. Emerging research on targeted pathways, including oxytocin and ghrelin signaling, holds promise for innovative treatments addressing hyperphagia and behavioral symptoms. This chapter provides a comprehensive overview of PWS's clinical features, natural history, and molecular underpinnings, underscoring the importance of early diagnosis, multidisciplinary care, and precision medicine in optimizing outcomes and enhancing the quality of life for individuals with PWS.