A neonate is noted to have a white reflex (leukocoria) in the right eye. Ultrasound B-scan shows a highly calcified intraocular mass with posterior shadowing. The lesion is unilateral and the child is 18 months old. Genetic testing of the tumor is planned. The gene involved in SPORADIC unilateral retinoblastoma is mutated in BOTH alleles:

• A In the germline (inherited from a parent)
• B One allele in the germline, one allele in the somatic cell
• C Only in the somatic (tumor) cells — 'two-hit' somatic mutations ✓
• D In the TP53 gene on chromosome 17

Explanation

Sporadic unilateral retinoblastoma follows Knudson's two-hit hypothesis: both mutations (hits) occur as somatic mutations in the same retinal cell — no germline mutation is inherited. In contrast, hereditary bilateral retinoblastoma involves one germline mutation (inherited or de novo) in one allele of RB1 on chromosome 13q14, requiring only one somatic hit in the second allele. Sporadic unilateral cases have two somatic hits in the tumor cells only, with no increased risk of second malignancies or transmission to offspring. The gene involved is RB1, not TP53.

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

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Written and medically reviewed by the StethoPrep medical team.