Introduction: Retinoblastoma due to germline mutation has a greater risk of bilateral presentation, and multifocal or extraocular involvement. In solitary unilateral retinoblastoma, the inheritance pattern is less understood and assumed to be somatic. We assessed the likelihood of germline inheritance in children with unilateral retinoblastoma and whether it varies based on age at presentation.
Methods: This was a retrospective case study assessing 482 consecutive patients with solitary unilateral retinoblastoma at Wills Eye Hospital between 1972 and 2020 for the likelihood of germline inheritance based on age at presentation (≤1 year vs. >1 year). Germline inheritance was deemed likely if there was a family history of retinoblastoma, positive genetic testing, and/or progression to bilateral retinoblastoma. Only patients with >1-month follow-up were included. Chi-square test and Odds Ratio analyses were performed.
Results: 465 of the 482 patients had sufficient follow-up data. 16% (n=72) of all patients, and 29% (n=37) of patients ≤1 year of age with unilateral retinoblastoma were likely to have germline disease (p=0.001). When compared to patients >1 year of age (n=339), patients ≤1 year (n=126) demonstrated a greater likelihood of germline inheritance with a 2.96 odds ratio ([1.55 – 5.65]).
Discussion: The inheritance of unilateral retinoblastoma is poorly understood. We found that 16% of children with unilateral retinoblastoma likely have germline inheritance, with a greater likelihood in children ≤1 year of age. Therefore, early assessment of inheritance and genetic testing of unilateral retinoblastoma may uncover germline disease and potential bilateral progression, for which a more conservative management approach to preserve vision should be considered.
Calotti, Martin; Shields, MD, Carol L.; Dockery, MD, MPH, Philip; Ruben, Megan; Yaghy, MD, Antonio; Sunday, Madalyne A.; Duffner, Emily R.; Levin, Hannah J.; Taylor, Olivia S.; Lally, MD, Sara E.; and Shields, MD, Jerry A., "Likelihood of Germline Mutation with Solitary Unilateral Retinoblastoma Based on Patient Age at Presentation. A Real-World Analysis of 482 Consecutive Patients." (2021). Phase 1. Paper 40.