A 14-month-old girl presents with leukocoria of both eyes. Examination shows multifocal retinal tumors bilaterally. Her mother was treated successfully for unilateral retinoblastoma in childhood. The inheritance pattern and penetrance of the underlying condition are best described as:

• A Autosomal recessive with complete penetrance
• B X-linked dominant with complete penetrance
• C Autosomal dominant with incomplete penetrance, due to a germ line RB1 mutation ✓
• D Autosomal dominant with complete penetrance, due to an RB1 promoter methylation defect only

Explanation

Hereditary retinoblastoma follows autosomal dominant transmission because inheriting one defective RB1 allele leaves each retinal cell one hit away from transformation; the second allele is lost somatically, fulfilling Knudson's two-hit hypothesis. Penetrance is about 90 percent, not complete. Hereditary cases are characteristically bilateral and multifocal with earlier onset, whereas sporadic cases require two somatic hits in one clone and are typically unilateral and unifocal, which distinguishes them from this child's presentation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.