What is the most appropriate next step in management for a 10‑year‑old child who recently recovered from an upper‑respiratory infection and has a family history of leukemia in an uncle and retinoblastoma in a brother?

Referral to Ophthalmology for Retinoblastoma Screening

The most appropriate next step is referral to ophthalmology (Option C) for retinoblastoma screening, given the brother's diagnosis of retinoblastoma, which places this child at elevated risk for hereditary disease requiring dedicated ophthalmic surveillance. 1, 2

Clinical Reasoning

Why Ophthalmology Referral is Critical

• Hereditary retinoblastoma risk: A sibling with retinoblastoma indicates this child has approximately 45% probability of carrying a germline RB1 pathogenic variant if the affected brother has hereditary disease 1
• High-risk classification: Children with a sibling diagnosed with retinoblastoma are considered "at risk" and require dedicated ophthalmic screening above population risk 2
• Time-sensitive intervention: Early detection through surveillance before leukocoria develops dramatically improves ocular survival (58% of screened patients diagnosed at Reese-Ellsworth group 1 vs. poor outcomes when leukocoria is the presenting sign) 3
• Genetic counseling integration: Ophthalmology referral should include genetic counseling and RB1 testing to clarify this child's actual risk and guide examination frequency 1, 2

Why Other Options Are Inappropriate

CBC (Option A) is not indicated:

• The uncle's leukemia does not establish a hereditary cancer syndrome requiring hematologic screening in this asymptomatic 10-year-old 4
• Respiratory viral infections in children with leukemia are common but this child does not have leukemia and has already recovered from the URTI 4
• No clinical indication exists for CBC in a well child 2 weeks post-URTI

CXR (Option B) is not indicated:

• The URTI has resolved and the child is asymptomatic
• No respiratory symptoms, fever, or clinical findings warrant chest imaging 5, 6
• Routine imaging for uncomplicated viral URIs is explicitly not recommended 5, 6

BRCA 1&2 testing (Option D) is not indicated:

• BRCA mutations are associated with breast, ovarian, prostate, and pancreatic cancers—not retinoblastoma or childhood leukemia 1
• Retinoblastoma is caused by RB1 gene mutations, not BRCA 1
• The family history does not suggest a BRCA-associated cancer syndrome

Recommended Screening Protocol

Initial Ophthalmology Evaluation Should Include:

• Dilated funduscopic examination by an ophthalmologist experienced in retinoblastoma screening 2, 3
• Genetic counseling to discuss RB1 testing for both the affected brother and this at-risk sibling 1, 2
• Risk stratification based on whether the brother's retinoblastoma was unilateral or bilateral, and genetic testing results 2

Examination Frequency Based on Risk:

• High-risk children (confirmed RB1 mutation carrier): Examinations under anesthesia every 1-2 months until age 2 years, then every 3-4 months until age 3-4 years 2
• Intermediate-risk children (sibling with retinoblastoma, genetic status unknown): Examinations every 2-3 months until genetic testing clarifies risk 2
• Low-risk children (sibling tested negative for familial RB1 mutation): Return to population-level screening 2

Critical Timing Considerations

• Age matters: Most hereditary retinoblastoma presents before age 24 months, but this 10-year-old still requires evaluation as late presentations can occur 7
• Bilateral disease risk: If the brother had bilateral retinoblastoma, this strongly suggests germline RB1 mutation and higher risk for this sibling 1
• Surveillance prevents blindness: Detection before leukocoria develops correlates with 58% diagnosis at early stage (group 1) versus only 4-29% ocular survival when leukocoria is the presenting sign 3

Common Pitfalls to Avoid

• Do not dismiss the family history because the child is 10 years old—while most cases present earlier, screening is still warranted 2, 7
• Do not order genetic testing without ophthalmology involvement—genetic counseling should be coordinated with retinoblastoma screening 1, 2
• Do not assume the uncle's leukemia is related—focus on the retinoblastoma risk, which is the immediate concern requiring action 1
• Do not delay referral for "routine" pediatric screening—dedicated ophthalmic surveillance by specialists is required for at-risk children 2, 3