Which of the following is a chromosomal abnormality?

• A. Sickle cell disease
• B. Cystic fibrosis
• C. Huntington disease
• D. Down syndrome (trisomy 21)

Answer: (D)

Understanding chromosomal abnormalities involves changes to the number or structure of whole chromosomes. Down syndrome is a classic example: there is an extra copy of chromosome 21, so the individual has trisomy 21. This changes the chromosome count (47 instead of 46) and is detectable on a karyotype, which is why it fits as a chromosomal abnormality.

The other conditions are due to mutations within single genes rather than changes in whole chromosomes. Sickle cell disease arises from a single base change in the beta-globin gene, while cystic fibrosis results from mutations in the CFTR gene. Huntington disease is caused by an expansion of a trinucleotide repeat within the HTT gene. In each case, the chromosome number is normal, so these are gene-level mutations, not chromosomal abnormalities.