Danish retinoblastoma patients 1943-2013 - genetic testing and clinical implications.

Background: In heritable retinoblastoma there is a 50% risk of transmitting the RB1 mutation, and offspring carriers have more than 90% risk of developing retinoblastoma. Today, all newly diagnosed retinoblastoma patients in Denmark are screened for mutations in RB1, as opposed to only a minority of patients diagnosed before DNA testing was offered. Knowledge of heredity increases the chance of early diagnosis in offspring, leading to improved prognosis. We present data from the Danish retinoblastoma patients that emphasize the need for genetic counseling and RB1 screening in all untested retinoblastoma survivors.
Material and Methods: Data are extracted from The Danish Ocular Oncology Group Database, a national population database containing data on all Danish retinoblastoma patients since 1943.
Results: In total 323 retinoblastoma patients have been diagnosed between 1943 and 2013. Since 1963, the rate has been stable around 1 per 14 000 live births with 95% of the patients surviving their retinoblastoma. Stratifying data on the time of diagnosis and status of genetic testing, the number of screened patients gradually increased from 5% in the beginning of the period to 96% in the last five-year period. A cohort of 181 retinoblastoma survivors with sporadic disease (15% heritable) did not receive genetic testing. Since the introduction of routine testing, one of 14 sporadic unilateral patients tested (7%) has been identified with a germline mutation. Before routine testing, five additional sporadic unilateral patients have been identified as heritable.
Conclusion: Only a minority of Danish retinoblastoma patients diagnosed before routine genetic testing was offered have been RB1 screened. To counsel the remaining untested patients and their families sufficiently regarding the risk to offspring and elevated risk of second primary cancers, we recommend information and access to genetic counseling and RB1 screening. This has ethical, psychological and possible economic consequences, and should be handled with caution.