Retinoblastoma is a primary malignant intraocular tumour of childhood accounting for ~1% of tumours in infancy. In most cases, it arises as a consequence of the silencing/loss of both copies of the tumour suppressor gene RB1 in developing retinal cells. The incidence of sporadic retinoblastoma is 1 in 15, 000–20,000 live births, with no gender or racial predilection. The median age at presentation is under 12 months in heritable cases (i.e. individuals with a family history of the condition), and closer to 24 months in sporadic cases. Presentation after the age of 6 years is extremely rare, although there are isolated reports of cases presenting as late as 26 years. Heritable retinoblastoma is prototypical of a cancer susceptibility syndrome. Affected individuals carry a single pathogenic copy of the RB1 gene that predisposes to retinoblastoma formation. All individuals with bilateral retinoblastoma carry such a pathogenic RB1 allele. Importantly, they also have a risk of developing other cancers and lifelong surveillance is required. Nearly 20% of individuals with unilateral retinoblastoma carry a pathogenic RB1 allele that can be transmitted to their children. For a unilaterally affected person with no detectable pathogenic allele with high sensitivity testing, the chance of having heritable retinoblastoma is <1%. Early recognition and diagnosis, alongside effective/optimised multidisciplinary care, results in a 95% cure rate for affected individuals. By contrast, delayed diagnosis results worldwide in around 70% mortality. Understanding the genetics of retinoblastoma has enabled clinicians to develop targeted screening guidelines based on genetic risk, minimising unnecessary screening exams, and focusing resources on individuals at greatest risk.
Clinical Ophthalmic Genetics and Genomics 2022, Pages 457-463,