What is the recurrence risk for Down syndrome (Trisomy 21) in a subsequent pregnancy when the mother is a balanced translocation carrier (14;21)?

Explanation

## Recurrence Risk in Balanced Translocation Carriers **Key Point:** When a **mother** carries a balanced 14;21 Robertsonian translocation, the empirical recurrence risk for Down syndrome in a subsequent pregnancy is **10–15%** (Option A). This is lower than the theoretical ~33% predicted by meiotic segregation analysis, due to selection against aneuploid gametes and embryos. ### Mechanism of Increased Risk A balanced translocation carrier has 45 chromosomes but is phenotypically normal because no genetic material is lost. However, during meiosis, unequal segregation of the translocated chromosomes can produce: 1. **Gametes with trisomy 21** (extra chromosome 21 material) → Down syndrome offspring 2. **Gametes with monosomy 21** (loss of chromosome 21) → Usually lethal (miscarriage) 3. **Normal or balanced gametes** → Normal or carrier offspring ### Recurrence Risk by Parental Carrier Status | Carrier Parent | Recurrence Risk for Down Syndrome | | --- | --- | | Mother (14;21 translocation) | **10–15%** | | Father (14;21 translocation) | 3–5% | | Mother (21;21 translocation) | ~100% (all viable offspring are trisomic) | | Father (21;21 translocation) | ~0% (very rare viable offspring) | **High-Yield:** Maternal carriers have a **higher recurrence risk** than paternal carriers because the egg is arrested in meiosis I and segregation errors are more common. Paternal carriers have lower risk because sperm are continuously produced and selection against aneuploid sperm may occur. **Clinical Pearl (Thompson & Thompson Genetics / Park's Textbook):** The empirical recurrence risk for a **maternal** 14;21 Robertsonian translocation carrier is **10–15%** (Option A). Option B (25–30%) does not correspond to any standard reference for this scenario. Option C (1–2%) represents the general population risk for older mothers, not translocation carriers. Option D (50%) is not applicable here. **Mnemonic:** **MAT-HIGH, PAT-LOW** — Maternal translocation carriers have higher recurrence risk (~10–15%); paternal carriers have lower risk (~3–5%). ### Clinical Management - Prenatal diagnosis (amniocentesis, CVS, or NIPT) is recommended for all pregnancies in translocation carriers - Genetic counseling before conception is essential - Partner karyotyping should be performed to exclude balanced translocation in the father