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.