A 2-year-old boy with Down syndrome is referred for genetic counseling. Karyotyping reveals 46 chromosomes with a Robertsonian translocation der(14;21). The structure marked **B** in the diagram represents a balanced Robertsonian (14;21) translocation carrier. Parental karyotyping shows the mother is a balanced carrier. What is the empiric recurrence risk for Down syndrome in future pregnancies of this couple?

Question

Accepted Answer

D. 10-15% recurrence risk. ## Why 10-15% recurrence risk is correct

When the **mother is a balanced Robertsonian (14;21) translocation carrier** (structure **B**), the empiric recurrence risk for Down syndrome in future pregnancies is **10-15%**. This is significantly higher than the 1% recurrence risk seen with free trisomy 21. The elevated risk occurs because during maternal meiosis, unbalanced gametes can form carrying both a normal chromosome 21 and the der(14;21), resulting in effective trisomy 21 in the offspring. Although theoretical risk is ~33% (1 in 3 liveborn outcomes), empiric risk is lower due to in-utero loss of other unbalanced conceptions. Maternal carriers have higher recurrence risk than paternal carriers (1-3%) because of selection against paternal sperm carrying unbalanced material (Thompson & Thompson Genetics in Medicine 8e).

## Why each distractor is wrong

- **1% above maternal age-related background risk**: This is the recurrence risk for free trisomy 21 (non-disjunction), not translocation Down syndrome. Free trisomy 21 accounts for ~95% of Down syndrome cases and has minimal recurrence risk.
- **3-5% recurrence risk**: This approximates the recurrence risk when the father is a balanced carrier (~1-3%), not the mother. Maternal carriers have substantially higher risk due to meiotic segregation patterns favoring unbalanced gamete formation.
- **100% recurrence risk**: This applies only to the rare der(21;21) Robertsonian translocation (two chromosome 21s fused), where every viable gamete carrying the translocation results in trisomy 21. The der(14;21) translocation has much lower recurrence risk.

**High-Yield:** Balanced Robertsonian (14;21) carrier mothers have 10-15% recurrence risk; fathers have only 1-3% — maternal carriers are at much higher risk due to meiotic segregation patterns.

[cite: Thompson & Thompson Genetics in Medicine 8e]

Answer

A. 3-5% recurrence risk

Answer

B. 1% above maternal age-related background risk

Answer

C. 100% recurrence risk

Explanation

Why 10-15% recurrence risk is correct

Why each distractor is wrong

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