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Updated: Sep 13, 2025
Reconstruct Human Retinoblastoma In Vitro
Published on: October 11, 2022
Late-Onset Retinoblastoma: Clinical and Genetic Features in Children Presenting Over 5 Years Old
William I Evans1, Barrett N Thompson2, Benjamin A King1
1Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee, Memphis, Tennessee; Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee.
Insights
Late-onset retinoblastoma in older children is often misdiagnosed. Genetic predisposition, including RB1 mutations, is more common than expected in these unilateral cases, impacting prognosis.
Area of Science:
- Ophthalmology
- Pediatric Oncology
- Clinical Genetics
Background:
- Retinoblastoma is typically diagnosed in infants and young children.
- Late-onset retinoblastoma (diagnosed at age ≥5 years) is rare but presents unique clinical and genetic challenges.
- Understanding these cases is crucial for accurate diagnosis and management.
Purpose of the Study:
- To define the clinical characteristics of retinoblastoma in children diagnosed at age five or older.
- To investigate the genetic factors associated with late-onset retinoblastoma.
- To identify potential reasons for delayed diagnosis in this patient group.
Main Methods:
- Retrospective chart review of children treated for retinoblastoma at a single institution (1999-2022).
- Analysis of demographics, genetic testing results, laterality, presenting symptoms, and prior misdiagnoses.
- Evaluation of tumor classification, treatments, outcomes, and RB1 gene status (germline mutations and promoter hypermethylation).
Main Results:
- 25 of 529 retinoblastoma patients (4.7%) were diagnosed at age ≥5 years (median age 6.0 years).
- Most presented with unilateral disease (96%), and 36% were initially misdiagnosed.
- Pathogenic germline RB1 mutations were found in 25% of tested patients, and RB1 promoter hypermethylation in 2 of 6 tumors.
Conclusions:
- Children diagnosed with retinoblastoma at an older age are frequently misdiagnosed prior to presentation.
- Germline genetic predisposition is more common in late-onset unilateral retinoblastoma than previously thought.
- These findings have significant implications for improving diagnostic accuracy, treatment strategies, and patient prognosis.
Objective:
To define the clinical features and genetics of children with retinoblastoma diagnosed at ≥5 years of age.
Design:
Retrospective review.
Subjects:
Children ≥5 years of age treated for retinoblastoma at a single institution between January 1999 and January 2022.
Methods:
A chart review including demographics, genetic testing, laterality, presenting signs and symptoms, initial diagnosis if not retinoblastoma, and procedures performed on affected eyes before diagnosis of retinoblastoma.
Main Outcome Measures:
Tumor classification, treatments and outcomes, and genetic data on tumors.
Results:
Of the 529 retinoblastoma patients identified, 25 (4.7%) were diagnosed at ≥5 years of age (median age 6.0 years, range 5.1-11.3 years). Most patients (24 of 25, 96%) presented with unilateral disease. Nine of 25 (36%) were misdiagnosed before presentation. Pathogenic RB1 germline mutations were identified in 6 of the 24 (25%) patients who underwent testing; 1 child had a positive family history. Further evaluation in 6 tumors (from 6 patients) identified hypermethylation of the RB1 gene promoter in 2 patients.
Conclusions:
Older children with retinoblastoma are commonly misdiagnosed before presentation. Germline predisposition to retinoblastoma was more common than anticipated for patients with late-onset unilateral disease. This may have important implications for treatment and prognosis.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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