Germline mutation risk in solitary unilateral retinoblastoma
Reviewed by Fiona Rowe

This study aimed to determine the true risk for germline mutation in a child presenting with solitary unilateral RB and whether this risk differs by age at presentation. This was a retrospective review of 482 cases from 1972-2020. Age groups were determined as 0-12 months, 12-24 months, 24-36 months and >36 months. Younger children were more likely to be of white race and with positive family history. Age group was not associated with gender or the involved eye. The youngest had lowest intraocular classification of retinoblastoma (ICRB) group, lowest rate of spontaneous regression at presentation, smaller mean tumour basal diameter and most posterior tumour location in the macula. The youngest had less primary enucleation and greater use of intravenous chemotherapy (IVC). Mean follow-up was 81.4 months. Three hundred and thirty-three children had formal genetic testing results. The youngest had longer follow-up, higher frequency of genetic testing positive for germline mutation, higher incidence of ultimate bilateral disease and higher incidence of likely germline disease. The youngest had increased odds of demonstrating RB germline mutation on genetic testing (OR 2.91), developing bilateral disease (OR 17.28), developing new tumours (OR 6.89) and demonstrating likely germline disease (OR 2.96). These ratios indicate the importance of possible germline disease in the youngest age groups. Limitations of this study are the potential underestimate as just 333 cases in the cohort had genetic testing. However, the authors also used acceptable alternative surrogates for genetic testing and therefore suggest these results represent useful real-world data. The authors conclude solitary unilateral RB carry a 16% likelihood of germline disease which is more prevalent in the younger age group >12 months although this also occurs to a lesser extent in older children.

Likelihood of germline mutation with solitary unilateral retinoblastoma based on patient age at presentation: analysis of 482 consecutive patients.
Shields CL, Dockery P, Ruben M, et al.
JOURNAL OF PEDIATRIC OPHTHALMOLOGY AND STRABISMUS
2021;58:355-64.