USMLE Step 1 · Biochemistry & Genetics

Trisomy 21 vs Trisomy 13 and trisomy 18

How to tell Trisomy 21 and Trisomy 13 and trisomy 18 apart when a board question makes them look alike.

Fastest separator

Trisomy 21 is Down syndrome with duodenal/cardiac/Alzheimer risk; trisomy 13 is midline/polydactyly; trisomy 18 is clenched fists and rocker-bottom feet.

Side by side

Trisomy 21Trisomy 13 and trisomy 18

Key clue

Trisomy 21 causes intellectual disability, flat facies, single palmar crease, duodenal atresia, endocardial cushion defects, Alzheimer risk, and AML/ALL risk.

Trisomy 13 causes holoprosencephaly, cleft lip/palate, polydactyly, and severe CNS defects; trisomy 18 causes clenched fists, rocker-bottom feet, micrognathia, and congenital heart disease.

Mechanism

Extra chromosome 21 dosage disrupts development, often from nondisjunction, Robertsonian translocation, or mosaicism.

Extra chromosome 13 or 18 dosage causes severe multisystem malformation with high infant mortality.

Labs and tests

Duodenal atresia, endocardial cushion defect, Brushfield spots, and early Alzheimer risk support trisomy 21.

Polydactyly/holoprosencephaly supports trisomy 13; clenched fists/rocker-bottom feet supports trisomy 18.

The trap

All cause developmental delay and congenital anomalies, so limb posture, midline defects, and duodenal/cardiac clues separate them.

The repair move

For trisomy stems, use the anomaly cluster rather than just intellectual disability.

Try a free question

Core

A newborn has hypotonia, upslanting palpebral fissures with epicanthal folds, a single transverse palmar crease, Brushfield spots on the iris, an endocardial cushion (AV canal) defect on echocardiogram, and feeding difficulties with bilious vomiting; double-bubble sign on abdominal X-ray suggests duodenal atresia. Which condition is most likely?

Show answer and explanation

Answer: A. Trisomy 21 (Down syndrome). Trisomy 21 features include hypotonia, upslanting palpebral fissures, single palmar crease, Brushfield spots, endocardial cushion (AV septal) defects, duodenal atresia, increased risk of leukemia (AML/ALL), and early-onset Alzheimer disease.

Why the other choices are tempting

B. Trisomy 13 features holoprosencephaly, cleft lip/palate, polydactyly, microphthalmia, omphalocele, and rocker-bottom feet with very poor survival.
C. Trisomy 18 features clenched fists with overlapping fingers, rocker-bottom feet, micrognathia, prominent occiput, and severe congenital heart disease with very poor survival.
D. Turner syndrome is 45,X with short stature, streak ovaries, webbed neck, coarctation of aorta in females, not the trisomy 21 phenotype.
E. Klinefelter syndrome is 47,XXY in tall males with hypogonadism, not infantile features described here.

Flashcards

Tap a card to flip it.

What clue supports Trisomy 21?

Choose Trisomy 21 when the stem gives this pattern: Trisomy 21 causes intellectual disability, flat facies, single palmar crease, duodenal atresia, endocardial cushion defects, Alzheimer risk, and AML/ALL risk.

What clue supports Trisomy 13 and trisomy 18?

Choose Trisomy 13 and trisomy 18 when the stem gives this contrasting pattern: Trisomy 13 causes holoprosencephaly, cleft lip/palate, polydactyly, and severe CNS defects; trisomy 18 causes clenched fists, rocker-bottom feet, micrognathia, and congenital heart disease.

Quick answers

What is the fastest way to tell Trisomy 21 from Trisomy 13 and trisomy 18?