Familial Retinoblastoma Surveillance

Retinoblastoma is the most common primary intraocular malignancy of childhood, caused by biallelic inactivation of the RB1 tumor suppressor gene (Knudson two-hit hypothesis). Hereditary (germline) retinoblastoma comprises 40% of cases, characterized by autosomal dominant inheritance, multifocal/bilateral disease, earlier age at diagnosis, and predisposition to second non-ocular malignancies. Sporadic cases (60%) typically present with unilateral disease without germline mutation.

Surveillance protocols for at-risk children (offspring or siblings of probands) begin at birth with examination at frequent intervals: every 2-4 weeks until 6 months, monthly to 1 year, every 2 months to 2 years, every 3 months to 3 years, every 4 months to 4 years, every 6 months to 7 years, and annually until early adulthood. Examinations include indirect ophthalmoscopy, often under anesthesia (EUA) with mydriasis, RetCam wide-field imaging, fluorescein angiography, and optical coherence tomography.

Genetic testing of probands identifies the RB1 mutation, enabling targeted prenatal or postnatal testing of at-risk relatives. Carriers without disease undergo intensive surveillance to detect tumors at the earliest stage when small tumors can be treated with focal therapies (laser, cryotherapy, intra-arterial chemotherapy, intravitreal chemotherapy, plaque brachytherapy) preserving vision. Survivors and germline carriers face elevated risk of second malignancies (osteosarcoma, soft tissue sarcoma, melanoma, lung cancer, breast cancer) requiring lifelong vigilance, sun protection, and avoidance of radiation therapy when possible.