The packet definition associates a predisposition to retinoblastoma with 13q14 cytogenetic abnormalities and notes that the inherited form is accompanied by increased risk of secondary nonocular malignancies such as osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma. No genes are listed in the packet's gene field, and no inheritance patterns are recorded there. The GeneReviews chapter states that heritable retinoblastoma is an autosomal dominant disorder. It describes most individuals with heritable retinoblastoma as simplex cases, meaning the only known affected person in the family. According to GeneReviews, most individuals with bilateral tumors who are simplex cases have heritable disease resulting from a de novo germline pathogenic variant, while some inherit the variant from an unaffected parent who may be mosaic or may carry a reduced-penetrance variant, and some inherit it from an affected parent. GeneReviews presents the proportions of presentation as follows: about 60% of probands have a negative family history with unilateral disease, about 30% have a negative family history with bilateral disease, and about 10% have a positive family history.

According to GeneReviews, retinoblastoma is suspected in children with leukocoria, strabismus, a change in eye appearance, or reduced visual acuity. The diagnosis is described as established by retinal examination with full pupillary dilatation by an ophthalmologist or optometrist, with confirmation and determination of disease extent through examination under anesthesia. Ocular imaging is described as able to help confirm the diagnosis, and pathology is described as not required. GeneReviews notes that biopsy may cause the tumor to spread beyond the eye. Heritable retinoblastoma is described as established in a proband with retinoblastoma or retinoma and a family history, while most individuals have no family history and molecular genetic testing for a germline pathogenic variant is the described way to determine whether the disease is heritable. Testing approaches listed include single-gene sequence analysis and deletion/duplication analysis on blood or tumor DNA, and chromosomal microarray. GeneReviews lists several conditions that can clinically simulate retinoblastoma, including tuberous sclerosis complex, Norrie disease, incontinentia pigmenti, familial exudative vitreoretinopathy, Von Hippel-Lindau syndrome, and ocular infection with Toxocara canis. The packet lists no newborn screening information for this condition.

The packet lists a cyclophosphamide record with NDA approval type, an approval date of July 30, 2020, and an active market status; the packet does not state the indication for this record. Orphan drug designations, which are not approvals, are recorded in the packet for several investigational products with an indication of treatment of retinoblastoma. These include episcleral topotecan, topotecan, two melphalan products, an adenovirus-based product encoding human PH20, an MDM2/HDM2-directed agent, thioureidobutyronitrile, and a small-molecule compound from Oxular Ltd. The GeneReviews management section describes treatment goals in order of priority as preservation of life and then sight. Optimal treatment is described as complex, with specialists from ophthalmology, pediatric oncology, pathology, and radiation oncology collaborating. GeneReviews states that choice of treatment depends on factors including the number of tumor foci, tumor size and location, vitreous seeding, potential for useful vision, extraocular extension, and available resources. Treatment options for the eye listed there include enucleation, cryotherapy, laser, systemic or local ocular chemotherapy (including intra-arterial chemotherapy) combined with or followed by laser or cryotherapy, radiation using episcleral plaques, and, as a last resort, external beam radiotherapy. GeneReviews notes that radiation is limited where possible to reduce the lifetime risk of subsequent malignant neoplasms, and that treatment of those later neoplasms is not presently distinct from similar cancers arising without heritable predisposition. GeneReviews also describes published surveillance schedules for affected persons and persons at risk, with frequent follow-up eye examinations after successful treatment for early detection of newly arising intraocular tumors.

The packet does not provide a structured natural history field. The GeneReviews clinical description states that retinoblastoma of the eye is generally curable, whereas pinealoblastoma is described as rare and usually fatal. It also states that the incidence of subsequent malignant neoplasms is more than 50% in individuals with retinoblastoma who received external beam radiation therapy. Subsequent malignant neoplasms are described as usually manifesting in adolescence or adulthood. Outcomes for any individual are not certified in this packet.

ClinicalTrials.gov records in the packet include studies that are recruiting and studies that are active but not recruiting. Retinoblastoma-specific records include a phase 2 study of treatment given inside the eye, a protocol for intraocular retinoblastoma, a phase 2 expanded access trial, a study of the effect of multiple anesthesia exposures on cognitive function in affected children, and a clinical database and tissue repository. Broader records include CAR T cell immunotherapy studies for recurrent or refractory solid tumors in children and young adults, a pediatric tumor omics repository, a childhood cancer predisposition study, and an expanded newborn screening study. The packet's trial summary lists intervention categories of drug therapy, procedural interventions, medical devices, and other interventions, and indicates that gene therapy trials are present. Its publication landscape summary classifies basic science and preclinical work as the dominant research type.