GPAtlas🧭 When to suspect (and the screening pathway)
Down's syndrome (trisomy 21) is the most common chromosomal disorder, affecting around 1 in 700 live births. About 95% arise from non-disjunction (47,XX or 47,XY, +21), roughly 4% from a translocation (most often a Robertsonian translocation involving chromosome 14), and 1–2% from mosaicism (often a milder phenotype). Crucially, the great majority of Down's syndrome is sporadic and not inherited – non-disjunction, mosaicism and most translocations arise de novo; only a minority of translocation cases (around a quarter, so roughly 1% of all cases) are inherited from a parent carrying a balanced translocation. The single dominant risk factor is advanced maternal age – the chance rises from roughly 1 in 1,500 at age 20 to about 1 in 350 at 35 and steeply thereafter – but a baby with Down's syndrome can be born to a mother of any age.
There are two routes to suspicion: antenatal screening, and postnatal recognition of the characteristic newborn. After birth, the clues are a constellation rather than any single sign – hypotonia (floppiness), a flat facial profile, upslanting palpebral fissures, a single transverse palmar crease and a sandal-gap between the first and second toes. The key primary-care skills are to confirm the diagnosis and its genetic mechanism, screen early for treatable complications, and deliver lifelong scheduled surveillance.
| Test | When offered | What it assesses |
|---|---|---|
| Combined test (test of choice) | 11+2 to 14+1 weeks | Nuchal translucency + PAPP-A + free beta-hCG. Screens for T21, T18 and T13. |
| Quadruple test | 14+2 to 20+0 weeks | Used if too late for the combined test or nuchal translucency cannot be measured. AFP, uE3, free beta-hCG, inhibin-A. Screens for T21 only. |
| NIPT (cell-free DNA) | After a higher-chance result | Offered following a higher-chance result (1 in 2 to 1 in 150) on the combined or quadruple test. Highly sensitive but still a screening test. |
| CVS / amniocentesis | After higher-chance / NIPT | The only way to confirm. Fetal karyotype from chorionic villi (CVS, from ~11 weeks) or amniotic fluid (amniocentesis, from ~15 weeks). |
Source: NHS Fetal Anomaly Screening Programme · Genomics Education Programme (NHS)
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