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. Of all cases:
• 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).
• 1–2% from mosaicism (often a milder phenotype).
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 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.
• 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
• A sandal-gap between the first and second toes
Once suspected:
• Confirm the diagnosis and its genetic mechanism
• Screen early for treatable complications
• 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 • Alpha-fetoprotein (AFP), uE3, free beta-hCG, inhibin-A • Screens for T21 only |
| Non-invasive prenatal testing (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)
🔒 Sign up free to read the full topic
You're viewing a free preview. Create a free account to unlock the rest.
Sign up free →Sample topics are open to everyone in the Free Sample Bundle.