Virginia Commonwealth University

VCU Massey Cancer Center

What causes retinoblastoma?

Retinoblastoma occurs due to mutations in a tumor suppressor gene (called RB1) located on chromosome 13. Two mutations (or gene changes) are necessary to “knock-out” this gene, and cause uncontrolled cell growth. In inherited retinoblastoma (40 percent of the cases), the first mutation is inherited from a parent, while the second occurs during the development of the retina. In sporadic retinoblastoma (60 percent of the cases), both mutations occur during development of the retina. Sporadic means “occurs by chance.” Alterations in the RB1 gene also have been found in other tumors, including osteosarcoma and breast cancer.

Most children with inherited retinoblastoma generally have tumors involving both eyes. (In fact, all cases involving both eyes should be considered hereditary). The RB1 gene is an autosomal dominant gene, which means that both males and females are equally affected, and there is a 50/50 chance, with each pregnancy, for a parent to transmit the gene to a child. When a child inherits the gene, there is a 75 percent to 90 percent chance for the second mutation to occur, resulting in retinoblastoma, meaning that some children who inherit the mutation may never get the second mutation, and may, therefore, never develop retinoblastoma. (They can still transmit the gene to their offspring, however, so that their children could develop the disease.)

Consider the following statistics:

  • 70 percent to 75 percent of retinoblastoma cases involve one eye (unilateral). Of these, 15 percent to 20 percent are inherited and the remainder are sporadic.
  • 25 percent of retinoblastoma cases are bilateral (both eyes) and hereditary. 
  • 15 percent of retinoblastoma cases are unilateral (one eye) and hereditary.
  • 60 percent of retinoblastoma cases are unilateral (one eye) and sporadic (non-hereditary).

Any individual with a positive family history of retinoblastoma may want to seek genetic counseling to identify the specific risks of passing the gene or disease to their children.