Hereditary Retinoblastoma (RB) – RB1 gene

Baby Detect > Ophtalmology > Hereditary Retinoblastoma (RB) – RB1 gene

Also known as: Familial retinoblastoma, Bilateral retinoblastoma, Trilateral retinoblastoma, and unilateral retinoblastoma

– OMIM#180200 https://omim.org/entry/180200

1. The disease

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

2. The symptoms

RB manifests most often in young children (90% of cases <3 years old). Lack of early signs or symptoms does not exclude the diagnosis.

  • Hereditary RB refers to those that arise due to a genetic predisposition (not always related to the family history); most of these patients have a bilateral disease and they are at increased risk to develop secondary tumors, mainly sarcoma but also pineoblastoma/supra-sellar tumor (both named ”trilateral retinoblastoma”), glial tumor, melanoma, and carcinoma.
  • Early clinical signs are leukocoria and strabismus. RB is most often painless, and children rarely complain of visual impairment despite its rapid progression towards loss of vision in the affected eye. In later stages, rarely seen in high income countries (HIC), intracranial dissemination and hematogenous metastasis, mainly to bones and bone marrow, are observed and are life-threatening.
  • Other rare signs include inflammation of the anterior chamber of the eye, vitreous haemorrhage, non-hematogenous retinal detachment, neovascular glaucoma and orbital cellulitis.

3. Actions to take in case of early diagnosis

  • The diagnosis of retinoblastoma 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.
  • Early diagnosis and treatment of retinoblastoma and non-ocular tumors can reduce morbidity and increase longevity; care is best provided by multidisciplinary teams of specialists including ophthalmology (see Ophthalmology Center list), paediatric 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.
  • Conservative treatments for at least one eye are possible in most bilateral cases and increasingly used in unilateral cases. Laser treatment alone or combined with systemic chemotherapy, cryotherapy and brachytherapy are very efficient tools, and newly developed chemotherapy using intra-arterial and/or intravitreous delivery. Enucleation is still frequently used in large unilateral RB as well as in bilateral with large unilateral tumor. External beam radiotherapy is now avoided (risk of late effects, including second cancers in irradiated field).
  • Vital prognosis is excellent in RB. Visual prognosis is dictated by tumor location and size at diagnosis (macular involvement has a poor visual prognosis). Eye preservation is possible with early diagnosis. After conservative treatment, visual prognosis depends on macular involvement.
  • Agents/circumstances to avoid: Limiting exposure to DNA-damaging agents (radiation, tobacco, and UV light) may reduce the excess cancer risks in H1 survivors of heritable retinoblastoma.
  • Genetic counselling should be offered to at-risk family members.

4. For more information: