Introduction
Prader-Willi Syndrome (PWS) is a complex genetic disorder caused by the loss of function of specific genes in chromosome 15. It is characterized by a range of physical, mental, and behavioral features, and is most commonly known for causing a constant sense of hunger leading to excessive eating and life-threatening obesity. The syndrome presents a unique combination of endocrine, neurological, and psychological symptoms, making its management a multidisciplinary challenge.
Pathophysiology
The genetic basis of PWS involves the loss of paternal copies of imprinted genes on chromosome 15q11-q13. This loss leads to a deficiency of certain proteins necessary for normal body function, affecting the hypothalamus, which plays a key role in hunger, satiety, and hormone regulation. The exact mechanisms linking the genetic abnormalities with the diverse clinical features remain an area of active research, with a focus on understanding the role of hypothalamic dysfunction.
Clinical Presentation
Individuals with PWS typically exhibit hypotonia and feeding difficulties in infancy, followed by excessive eating and rapid weight gain starting around age 2-4 years. Developmental delays, cognitive impairment, and behavioral problems are commonly seen. Endocrine disturbances include growth hormone deficiency, hypogonadism, and hypothyroidism. The characteristic facial features, small hands and feet, and short stature are other notable clinical signs.
Diagnostic Approach
The diagnosis of PWS is confirmed through genetic testing, which identifies the specific chromosomal changes responsible for the syndrome. Methylation analysis is the most common diagnostic test used to detect the absence of paternal gene expression on chromosome 15. Early diagnosis is crucial for managing symptoms and improving quality of life, and it involves a combination of clinical assessment and genetic testing.
Management and Prognosis
Management of PWS is lifelong and multidisciplinary, focusing on controlling food intake, treating endocrine disorders, and addressing the behavioral and psychiatric issues. Growth hormone therapy plays a significant role in improving growth, body composition, and physical strength. Early intervention, including physical, occupational, and speech therapies, is vital for developmental support. While there is no cure, appropriate management can significantly improve the quality of life and lifespan of individuals with PWS.
