Age at retinoblastoma diagnosis aids genetic risk stratification for bilateral conversion
- 27-03-2026
- Retinoblastoma
- Editor's Choice
- News
medwireNews: Considering age at diagnosis alongside genetic risk stratification could help identify children with unilateral retinoblastoma who are likely to convert to metachronous bilateral disease, show findings published in JAMA Ophthalmology.
Peiquan Zhao (Xin Hua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, China) and colleagues found that patients positive for the retinoblastoma transcriptional corepressor 1 (RB1) gene, biallelic inactivation of which causes retinoblastoma, were at “very low” risk for metachronous bilateral conversion if they were diagnosed at 9 months or older.
“Risk-adapted follow-up may help identify metachronous disease earlier among higher-risk children. At the same time, it may reduce the frequency of examinations in lower-risk patients, thereby minimizing burden without compromising safety,” they say.
The retrospective study was conducted at a tertiary center in Shanghai, China, and involved 1108 children (median age 22.2 months; 53.3% boys) diagnosed with unilateral retinoblastoma between July 2010 and October 2024.
On peripheral blood tests performed using next-generation sequencing combined with multiplex ligation-dependent probe amplification, 5.6% of children tested positive for pathogenic or likely pathogenic RB1 gene variants, 22.9% tested negative, and 71.5% were untested.
The age of the children at diagnosis differed depending on the RB1 gene subgroup, with those testing positive for variants aged a median of 14 months, while patients who were negative or untested had median ages of 24.1 months and 22.3 months, respectively.
Over a median follow-up of 43.4 months, 24 (2.2%) children developed metachronous bilateral disease. Children who were RB1 variant-positive were the most likely to convert, at a rate of 24.2%, compared with 1.6% of RB1 variant-negative children and 0.6% of untested children. The study authors note that most conversions occurred in the first 24 months.
When the researchers grouped the RB1 variant-positive patients into four subgroups according to penetrance class (high vs low) and whether genetic variation was inherited via germline or through mosaicism, they found age differences between the children with and without bilateral conversion.
Specifically, individuals with germline high-penetrance RB1 variants who developed bilateral disease (n=6) were younger at diagnosis than those who maintained unilateral disease (n=22), at median ages of 2.43 versus 26.15 months. The corresponding rates for germline low-penetrance RB1 carriers who did and did not develop bilateral disease (n=16 and 3, respectively) were 2.69 and 18.04 months.
Similarly, children carrying mosaic high-penetrance RB1 variants who converted to bilateral disease (n=3) were a median of 3.38 months old at diagnosis, whereas those who did not (n=7) were a median of 17.25 months, and there were insufficient numbers of mosaic low-penetrance RB1 variant carriers to statistically compare those who did and did not convert.
“These findings indicate that converters were consistently much younger at initial presentation than nonconverters within each genetic subtype, whereas neither penetrance class nor mosaic status showed an association beyond age at diagnosis,” the team writes.
Further stratification of the children into 3-month age bands revealed that all conversions to bilateral disease in children positive for RB1 variants occurred in those who were diagnosed before the age of 9 months and within 24 months of the initial diagnosis.
“Beyond this window, we did not observe additional events in this subgroup,” Zhao and team point out.
“RB1 variant–positive children diagnosed at or after 9 months had very low conversion risk across surveillance. RB1 variant–negative children had overall low conversion risk, but rare late conversions occurred.”
They say that “[t]aken together, these data support surveillance that is triggered by genetic status and calibrated by age at diagnosis.”
But they acknowledge that external validation of the findings in diverse populations is needed, as is longer observation to “definitely characterize” late conversion patterns in children who are RB1 variant negative.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2026 Springer Healthcare Ltd, part of Springer Nature
