A 3-year-old child with Down syndrome is being evaluated for developmental delay and congenital heart disease. Which of the following is the most common chromosomal abnormality responsible for Down syndrome?

Explanation

## Chromosomal Basis of Down Syndrome ### Classification by Karyotype | Type | Frequency | Mechanism | Recurrence Risk | |------|-----------|-----------|------------------| | Free Trisomy 21 | 95% | Nondisjunction during meiosis | ~1% | | Robertsonian Translocation | 3–4% | Fusion of chromosome 21 with 14 (or 21;21) | 10–15% if mother is carrier | | Mosaic Trisomy 21 | 1–2% | Nondisjunction during early mitosis | ~1% | | Partial Trisomy 21 | <1% | Unbalanced translocation | Variable | **Key Point:** Free trisomy 21 (simple trisomy) accounts for **95% of all Down syndrome cases** and results from meiotic nondisjunction, most commonly during maternal meiosis I. ### Why Free Trisomy 21 is Most Common 1. **Nondisjunction is a random event** — occurs in ~0.1% of meioses, increasing with maternal age (especially >35 years). 2. **No prior familial predisposition required** — de novo occurrence in most cases. 3. **Viable karyotype** — presence of three copies of chromosome 21 is tolerated in utero and postnatally. **High-Yield:** The **maternal age effect** is critical: risk at age 20 is ~1/1500; at age 35 is ~1/350; at age 45 is ~1/30. This is the single strongest risk factor for free trisomy 21. ### Clinical Pearl Translocation Down syndrome (3–4% of cases) is the only form with **significantly elevated recurrence risk** (10–15% if mother is a balanced carrier). Prenatal counseling and karyotyping of parents is essential in translocation cases. **Mnemonic:** **"95-3-1-1"** — Free trisomy 95%, Translocation 3%, Mosaic 1%, Partial 1%.