Which test would best detect a balanced chromosomal rearrangement among prenatal tests?

• A. Karyotype
• B. FISH
• C. Chromosomal microarray
• D. PCR

Answer: (A)

Balanced chromosomal rearrangements rearrange parts of chromosomes without changing the total amount of genetic material, so the test needs to show the actual chromosome structure, not just copy number. A karyotype analyzes the entire chromosome complement in cultured fetal cells and uses staining to reveal the banding pattern, making it possible to see translocations, inversions, and other structural rearrangements. This genome-wide view is what allows detection of balanced changes that don’t affect copy number.

Chromosomal microarray, by contrast, detects gains or losses of DNA across the genome. Since balanced rearrangements don’t involve net DNA gain or loss, CMA often appears normal and misses these rearrangements. FISH can detect specific rearrangements with targeted probes but requires prior suspicion of a particular abnormality and isn’t as comprehensive for unknown or cryptic rearrangements. PCR would require exact knowledge of a breakpoint and cannot survey the whole genome.

So, to best detect balanced chromosomal rearrangements prenatally, evaluating the entire chromosome structure with a karyotype is the most effective approach.