A newborn male infant is diagnosed with Down syndrome. The karyotype notation marked **D** in the diagram reads 47,XY,+21. The parents are counseled about recurrence risk in future pregnancies. Based on this standard cytogenetic finding, what is the most likely mechanism of chromosome 21 nondisjunction and the recurrence risk in the next pregnancy?

Explanation

## Why "Meiosis I nondisjunction in maternal germ cells; recurrence risk ~1% above maternal-age baseline" is right The karyotype notation **D** (47,XY,+21) represents standard trisomy 21, which accounts for ~95% of Down syndrome cases. This karyotype results from nondisjunction during meiosis I, predominantly in maternal germ cells. The recurrence risk in future pregnancies is approximately 1% above the baseline risk for the mother's current age — a key distinction from the higher recurrence risks seen with Robertsonian translocations. This is the textbook standard for counseling families with standard trisomy 21 (Harrison 21e Ch 471; Nelson 21e). ## Why each distractor is wrong - **Meiosis II nondisjunction in paternal germ cells; recurrence risk ~5-10%**: While nondisjunction can occur in meiosis II, standard trisomy 21 arises predominantly from maternal meiosis I errors. Paternal nondisjunction accounts for only ~25% of cases, and the recurrence risk remains ~1% above baseline, not 5-10%. - **Robertsonian translocation inherited from balanced carrier father; recurrence risk ~1-2%**: The karyotype 47,XY,+21 is standard trisomy 21 (47 chromosomes total), not a translocation. Robertsonian translocations would show 46 chromosomes with 3 copies of 21q material. The 1-2% recurrence risk applies only if the father is a balanced carrier of a translocation. - **Postzygotic nondisjunction during early embryonic division; recurrence risk ~100%**: Postzygotic nondisjunction results in mosaic Down syndrome (~1-2% of cases), not standard trisomy 21. Mosaic karyotypes show a mixture of normal and trisomic cells. Recurrence risk for mosaic DS is not elevated above baseline (~1%), not 100%. **High-Yield:** Standard trisomy 21 (47,XY,+21 or 47,XX,+21) = maternal meiosis I nondisjunction in ~95% of cases; recurrence risk ~1% above maternal-age baseline (not 3-5% or higher — that's translocation carrier risk). [cite: Harrison 21e Ch 471; Nelson 21e]