PraderWillisyndrom

Prader-Willi syndrome (PWS) is a genetic disorder caused by loss of function of paternally expressed genes in the 15q11-q13 region of chromosome 15. This loss can occur through a paternal deletion, maternal uniparental disomy (two copies of chromosome 15 from the mother), or an imprinting defect that alters gene expression. PWS is one of several imprinting disorders affecting this region and is distinct from Angelman syndrome, which arises from a different parental origin of the same genes.

People with PWS appear normal at birth but typically have marked hypotonia and poor feeding in infancy, followed by excessive appetite and rapid weight gain in early childhood. Other features include short stature, hypogonadism, learning difficulties, behavioral problems, sleep apnea, scoliosis, and a range of endocrine issues. Without management, severe obesity and related health problems are common.

Diagnosis is confirmed by genetic testing. A DNA methylation test of the 15q11-q13 region can diagnose PWS even when the specific genetic cause is not identified. Further testing (fluorescence in situ hybridization or microarray) can distinguish deletion from maternal UPD or imprinting defects and guide recurrence risk counseling.

Management requires a multidisciplinary approach. Growth hormone therapy may improve height, body composition, and muscle tone. Nutritional management with strict, supervised caloric control and regular physical activity helps prevent obesity. Endocrine management, including assessment of gonadal function and possible hormone replacement during adolescence, is common. Treating sleep apnea, monitoring for diabetes and thyroid disease, and providing behavioral support are important components.

Genetically, the majority of cases arise from paternal chromosome 15q11-q13 deletion (about 70%), with maternal UPD accounting for roughly 25–30%, and imprinting defects comprising the remainder. Genetic counseling is recommended for families.