What is the most appropriate next step for a child with a recent upper respiratory tract infection (URTI) and a significant family history of cancer, including an uncle with leukemia and a brother with retinoblastoma?

Ophthalmology Referral for Retinoblastoma Screening

The most appropriate next step is C - refer to ophthalmology for retinoblastoma screening, given the brother's diagnosis of retinoblastoma which indicates potential hereditary disease requiring immediate evaluation of this child. 1

Rationale for Ophthalmology Referral

Family History Significance

• About 45% of children with retinoblastoma have hereditary disease due to germline RB1 pathogenic variants, which confer >90% risk of intraocular disease in an autosomal dominant manner 1
• Siblings of affected children are at substantial risk and require urgent ophthalmologic evaluation regardless of symptoms 1
• The brother's retinoblastoma diagnosis is the critical red flag here - this represents a high-genetic risk solid tumor type that should prompt immediate family screening 1

Timing is Critical

• Hereditary retinoblastoma risks begin in early infancy with high penetrance of retinal tumors requiring close intraocular surveillance 1
• Early detection through surveillance dramatically improves outcomes and may allow for eye-preserving treatments rather than enucleation 2
• Genetic counseling and testing should occur at the time of tumor diagnosis in the family, with siblings evaluated immediately 1

Why Other Options Are Inappropriate

CBC (Option A)

• The uncle's leukemia is not an indication for CBC screening in an asymptomatic child who recently had a benign URTI 1
• Leukemia surveillance with CBC is only indicated for children with known leukemia predisposition syndromes (Fanconi anemia, dyskeratosis congenita, severe congenital neutropenia, etc.), not based on family history alone 1
• The recent URTI is a common viral illness and does not suggest hematologic malignancy 3, 4

Chest X-ray (Option B)

• No indication exists for chest imaging in a child with resolved URTI and no respiratory symptoms 3, 4
• Chest X-ray would only be considered in children with fever and neutropenia or persistent/severe respiratory symptoms, neither of which applies here 1

BRCA Testing (Option D)

• BRCA1/2 mutations are not associated with retinoblastoma or childhood leukemia 1
• BRCA testing is indicated for hereditary breast/ovarian cancer syndromes, not pediatric malignancies like retinoblastoma
• The relevant gene for this family is RB1, not BRCA 1

Clinical Pitfalls to Avoid

• Do not dismiss family history of retinoblastoma as unrelated to this child's care - siblings require immediate screening regardless of symptoms 1
• Do not wait for symptoms to develop - retinoblastoma screening must be proactive as early detection is crucial for vision preservation 1
• Do not confuse different cancer predisposition syndromes - leukemia predisposition and retinoblastoma predisposition are distinct entities requiring different approaches 1
• The recent URTI is a red herring - it is a common benign viral illness unrelated to the cancer family history 3, 4