Regarding the genetics of retinoblastoma, a child has bilateral retinoblastoma. He has a germline mutation in the RB1 gene. His sibling is unaffected. What is the probability that the unaffected sibling carries the germline mutation (assuming the proband's mutation arose de novo in the germline)?

• A 50% (autosomal dominant inheritance)
• B 25% (autosomal recessive)
• C 0% since the sibling is clinically unaffected
• D ~6% for de novo germline mutations in siblings ✓

Explanation

Bilateral retinoblastoma implies germline (heritable) RB1 mutation. When the mutation is de novo in the proband (not inherited from parents), the risk to siblings from parental gonadal mosaicism is approximately 1-9% (estimated ~6% by population data). If either parent carries the germline mutation, risk to siblings is 50%. Germline RB1 mutation carriers have ~90% penetrance for retinoblastoma, so an unaffected sibling could still be a carrier in the parental transmission scenario. Genetic counselling and RB1 testing of parents is essential.

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.