Trisomy 21 occurs when nondisjunction during meiosis produces a gamete with an extra chromosome 21, resulting in 47 chromosomes instead of 46. The overexpression of genes on chromosome 21 leads to disrupted embryogenesis affecting the cardiac septum (endocardial cushion defects), craniofacial development, GI tract (duodenal atresia, Hirschsprung disease), and central nervous system (reduced neuronal density). Approximately 95% of cases are full trisomy 21, while 3-4% result from Robertsonian translocation and 1-2% from mosaicism. The nurse must coordinate comprehensive multidisciplinary care, manage cardiac and respiratory complications, perform developmental screening, and educate families on long-term health surveillance.