Down Syndrome: Genetic Basis, Epidemiology, and Key Facts

Down syndrome (trisomy 21) is the most common autosomal aneuploidy, occurring in ~1 in 700 live births.

Genetic Mechanisms

• Free trisomy 21 (95%): Meiotic nondisjunction (maternal 90%, paternal 10%).
• Robertsonian translocation (3–4%): 14;21 or 21;21 – can be inherited.
• Mosaicism (1–2%): Post-zygotic nondisjunction → milder phenotype.

Clinical Features

• Characteristic facies, hypotonia, single palmar crease, sandal gap.
• Intellectual disability (mild-moderate).
• Comorbidities: CHD (AVSD 40%), GI atresia, hypothyroidism, leukemia risk ↑, early Alzheimer’s.

Screening & Diagnosis

• Prenatal: cfDNA (NIPT) >99% sensitivity; diagnostic: CVS (10–13 wk), amnio (15–20 wk).
• Postnatal: Karyotype / FISH / microarray.

Key Facts

• Not caused by lifestyle, environment, or parental behavior.
• Not contagious.
• Life expectancy now >60 years with modern care.
• Early intervention, inclusive education, medical surveillance optimize outcomes.