Bit · Genetics
Trisomy 13 vs 18 vs 21
Three autosomal trisomies that all share advanced maternal age as a risk factor but split hard on phenotype and survival. The pivot is which body part is wrecked the worst.
Mechanism
All three are autosomal trisomies arising from meiotic nondisjunction, with risk rising sharply with maternal age. They differ in which organ systems they hit hardest:
- Trisomy 21 (Down) — the most common live-born trisomy. Survival into adulthood expected. Predominantly affects facial development, the heart (AV septal defect), the GI tract, and the brain.
- Trisomy 18 (Edwards) — second most common. Severely affects everything — most die in the first year. Classic clenched fists with overlapping fingers and rocker-bottom feet.
- Trisomy 13 (Patau) — least common. Midline defects dominate: holoprosencephaly, cleft lip/palate, polydactyly, microphthalmia. Most die in the first year.
Differentiator Table
| Trisomy 21 (Down) | Trisomy 18 (Edwards) | Trisomy 13 (Patau) | |
| Incidence (live birth) | ~1 in 700 | ~1 in 6,000 | ~1 in 10,000 |
| Survival | Adulthood | Most die <1 year | Most die <1 year |
| Face / head | Flat facies, slanting palpebral fissures, epicanthal folds, small ears, protruding tongue | Micrognathia (small jaw), prominent occiput, low-set ears | Cleft lip/palate, holoprosencephaly, microphthalmia, cutis aplasia |
| Hands / feet | Single transverse palmar (simian) crease, gap between 1st and 2nd toes | Clenched fists with overlapping fingers, rocker-bottom feet | Polydactyly, rocker-bottom feet |
| Heart | AV septal defect (endocardial cushion); VSD | VSD, ASD, PDA | VSD, ASD, dextrocardia |
| Other | Duodenal atresia, Hirschsprung, ↑ AML/ALL, early Alzheimer | Severe intellectual disability, kidney malformations | Holoprosencephaly, omphalocele, kidney cysts |
| Quad screen (2nd trimester) | ↓ AFP, ↓ estriol, ↑ hCG, ↑ inhibin A | ↓ AFP, ↓ estriol, ↓ hCG, normal inhibin A | Normal quad screen typically |
The Pivot
Three questions on inspection:
- Midline defect (cleft, holoprosencephaly, polydactyly)? → Patau (13).
- Clenched fists with overlapping fingers, rocker-bottom feet, micrognathia, dying in infancy? → Edwards (18).
- Flat face, slanting eyes, single palmar crease, AV septal defect, growing up? → Down (21).
Mnemonic for survival: 13 + 18 = 31 weeks, neither makes it past one year on average. 21 ages backwards into adulthood.
NBME-Style Stem
A newborn boy has cleft lip, polydactyly of the right hand, microphthalmia, and a holoprosencephalic brain malformation on MRI. Echocardiogram shows a VSD. Karyotype is pending. Which of the following is the most likely diagnosis?
Concept Anchor
Maternal nondisjunction at meiosis I produces three lookalike trisomies — the pivot is the organ pattern: midline → 13, clenched fists + rocker bottom + early death → 18, flat face + AV septal defect + adulthood → 21.