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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2000 Jul 18 [updated 2015 Nov 19].

Author information

Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany
Professor, University of Toronto, Head, Cancer Informatics, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada



Retinoblastoma (Rb) is a malignant tumor of the developing retina that occurs in children, usually before age five years. Rb develops from cells that have cancer-predisposing variants in both copies of RB1. Rb may be unifocal or multifocal. About 60% of affected individuals have unilateral Rb with a mean age of diagnosis of 24 months; about 40% have bilateral Rb with a mean age of diagnosis of 15 months. Heritable retinoblastoma is an autosomal dominant susceptibility for Rb. Individuals with heritable retinoblastoma are also at increased risk of developing non-ocular tumors.


The diagnosis of Rb is usually established by examination of the fundus of the eye using indirect ophthalmoscopy. Imaging studies can be used to support the diagnosis and stage the tumor. The diagnosis of heritable retinoblastoma is established in a proband with Rb or retinoma and a family history of Rb or by detection of a germline pathogenic variant in RB1.


Treatment of manifestations: Early diagnosis and treatment of Rb and non-ocular tumors can reduce morbidity and increase longevity; care is best provided by multidisciplinary teams of specialists including ophthalmology, pediatric oncology, pathology, and radiation oncology. Treatment options depend on tumor stage, number of tumor foci (unifocal, unilateral multifocal, or bilateral), localization and size of the tumor(s) within the eye(s), presence of vitreous seeding, the potential for useful vision, the extent and kind of extraocular extension, and the resources available. Treatment options include enucleation; cryotherapy; laser, systemic, or local ocular chemotherapy including intra-arterial chemotherapy combined with or followed by laser or cryotherapy; radiation therapy using episcleral plaques; and, as a last resort, external beam radiotherapy. Prevention of secondary manifestations: If possible, radiation (including x-ray, CT scan, and external beam radiation) should be avoided in individuals with heritable Rb to minimize the lifetime risk of developing late-onset second cancers. Surveillance: In children known to have an RB1 germline pathogenic variant: eye examination under anesthesia every three to four weeks until age six months, then less frequently until age three years. Clinical examinations with cooperative children are performed every three to six months until age seven years, then annually and eventually biannually for life. Individuals who have unilateral Rb without an identified heterozygous germline RB1 pathogenic variant are at risk for low-level mosaicism and should have regular clinical examination of the eyes, including clinical ultrasound. Individuals with retinomas are followed with retinal examinations and imaging every one to two years. To detect second non-ocular tumors in individuals with retinoblastoma, physicians and parents should promptly evaluate complaints of bone pain or lumps because of the high risk for sarcomas and other cancers; however, effective screening protocols have not yet been developed. Agents/circumstances to avoid: Limiting exposures to DNA-damaging agents (radiation, tobacco, and UV light) may reduce the excess cancer risks in survivors of heritable retinoblastoma. Evaluation of relatives at risk: Molecular genetic testing for early identification of asymptomatic at-risk children in a family reduces the need for costly screening procedures in those at-risk family members who have not inherited the pathogenic variant.


Heritable retinoblastoma is inherited in an autosomal dominant manner. Individuals with heritable retinoblastoma have a heterozygous de novo or inherited germline RB1 pathogenic variant. Offspring of affected individuals have a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the RB1 pathogenic variant has been identified in an affected family member.

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