Retinoblastoma: Genetic Counseling and Testing

Genetic counseling and testing for retinoblastoma (RB) pose unique challenges for clinicians and patients. Despite RB being a single-gene disorder, there are complexities in the genetic and clinical phenotype that can make providing guidance to patients and their families difficult. Retinoblastoma may present as a unilateral or bilateral disease. This laterality alone influences the likelihood of a germline pathogenic variant in the RB1 gene being present. All cases of bilateral RB harbor a germline RB1 pathogenic variant; however, in unilateral cases, a germline pathogenic variant is present approximately 15–20% of the time. Mosaicism and incomplete penetrance are other factors that may cloud the interpretation of a family history and recurrence risk estimates. Adult RB survivors with a germline RB1 pathogenic variant have an increased risk for other cancers; however, clear guidelines on cancer surveillance have yet to be established. Finally, with the advancements in genetic testing technology, molecular analysis is readily available to diagnose patients. One must keep in mind, though, that not all genetic tests are equal in their detection rates and sensitivities. It is important to be cognizant of the limitations still present when selecting and offering genetic testing to patients, in the interpretation of test results, and in the provision of recurrence risks.