A 3-year-old girl is referred to the ophthalmology clinic for screening after her 5-year-old brother was diagnosed with bilateral retinoblastoma 6 months ago. On dilated fundoscopy of both eyes, the girl has normal-appearing retinae with no masses, calcifications, or vitreous seeding. Genetic testing of the brother reveals a germline RB1 mutation. The girl's genetic testing is pending. What is the most appropriate management for this child?

Explanation

## Hereditary Retinoblastoma and Familial Screening This child has a 50% risk of carrying the same germline RB1 mutation as her affected brother, making her at high risk for bilateral retinoblastoma development. ### Genetic Risk and Penetrance **Key Point:** Germline RB1 mutations confer: - **Penetrance:** ~90% (90% of carriers develop retinoblastoma) - **Bilaterality:** ~75% of germline cases are bilateral - **Age of onset:** Usually before age 5; median age ~18 months for bilateral disease **High-Yield:** Siblings of children with germline RB1 mutations have a 50% chance of inheriting the mutation. Even if genetic testing is negative, clinical surveillance is recommended until age 5 because: - De novo mutations can occur - Genetic testing has ~5% false-negative rate - Tumours can develop rapidly in young children ### Surveillance Protocol for At-Risk Children **Mnemonic:** **SCREEN** = **S**ystematic **C**linical **R**etinal **E**xamination **E**very **N**ot-too-long interval | Timing | Method | Frequency | |--------|--------|----------| | Birth to age 5 | Dilated fundoscopy under GA | Every 2–4 weeks | | Age 5–7 (if negative) | Dilated fundoscopy ± imaging | Every 4–8 weeks | | Age 7+ (if negative) | Dilated fundoscopy | Every 6–12 months | | Age 16+ (if negative) | Annual dilated exam | Lifelong | ### Role of Imaging in Surveillance **Clinical Pearl:** While dilated fundoscopy is the primary screening tool, adjuvant imaging (B-scan ultrasound or MRI) is reserved for: - Detection of small lesions not visible on fundoscopy - Confirmation of suspected lesions - Assessment of posterior pole tumours - Monitoring for vitreous seeding or extraocular extension Imaging is NOT routine in asymptomatic children with normal fundoscopy. ### Why Prophylactic Enucleation Is Not Indicated **Warning:** Bilateral prophylactic enucleation is ethically and medically unjustified because: - The child currently has no evidence of disease - Modern chemoreduction and focal therapies preserve vision in most cases - Enucleation causes permanent blindness and should only be performed for Group E disease or failed chemoreduction - Early detection through surveillance allows eye-salvaging treatment ### Why Systemic Chemotherapy Is Not Indicated Chemotherapy is reserved for treatment of diagnosed intraocular or extraocular disease, not prophylaxis in asymptomatic children. Prophylactic chemotherapy exposes the child to unnecessary toxicity without proven benefit. ### Genetic Counselling **Key Point:** This family requires: - Confirmation of germline RB1 mutation status in the girl - Parental genetic testing to identify the carrier parent - Counselling about recurrence risk in future siblings (50% if parent is a carrier) - Discussion of long-term surveillance needs and vision-preserving treatment options [cite:Yanoff & Duker Ophthalmology 6e Ch 6.19; American Academy of Ophthalmology Retinoblastoma Guidelines 2023]