A couple has a child with cystic fibrosis (homozygous F508del). Both parents are carriers. On genetic counselling it is found that the maternal grandfather also has a child with CF from an unrelated first marriage. The grandfather is phenotypically normal. What is the probability that a subsequent child of the CF couple will be affected?

• A 1 in 2 (50%) — because the father was already confirmed carrier from having an affected child
• B 2 in 3 (67%) — after correcting for the prior probability that the grandfather was a carrier
• C 1 in 8 (12.5%) — risk adjusted for the extended pedigree using Bayes theorem
• D 1 in 4 (25%) — standard Mendelian autosomal recessive risk for each pregnancy regardless of family history of prior affected members ✓

Explanation

Once both parents are confirmed carriers (proven by having an affected CF child), the Mendelian risk for each subsequent pregnancy is 1 in 4 (25%), independently of birth order, prior affected children, or family history. Each conception is an independent event. Additional family history confirming carrier status in the grandfather does not alter the per-pregnancy recurrence risk for this specific couple. Bayes theorem is applied when carrier status is uncertain (using conditional probability based on unaffected siblings), not when carrier status is already confirmed. This is a classic autosomal recessive inheritance question about residual recurrence risk.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.