Retinoblastoma

Retinoblastoma is a rare type of eye cancer that develops in the retina, the part of the eye that detects light and color. Although this disorder can occur at any age, it usually develops in young children.

Most cases of retinoblastoma occur in only one eye, but both eyes can be affected. The most common sign of this disorder is a visible whiteness in the normally black pupil (the opening through which light enters the eye). This unusual whiteness is particularly noticeable in photographs taken with a flash, and is called "cat's eye reflex" or leukocoria. Other signs and symptoms of retinoblastoma include crossed eyes or eyes that do not point in the same direction (strabismus); persistent eye pain, redness, or irritation; and blindness or poor vision in the affected eye.

People with the hereditary form of retinoblastoma may also develop a tumor in the brain called pinealoma. Pinealoma develops in the pineal gland, which is located at the base of the skull. The presence of retinoblastoma and pinealoma together is called trilateral retinoblastoma. Later in life, people with hereditary retinoblastoma also have an increased risk of developing bone cancer (osteosarcoma), soft tissue cancers, a form of skin cancer called melanoma, and other types of cancer.

Retinoblastoma affects an estimated 1 in 15,000 to 20,000 live births. This disease is diagnosed in about 250 children per year in the United States. It accounts for about 3 percent of all cancers in children younger than 15 years.

Mutations in the RB1 gene are responsible for most cases of retinoblastoma. RB1 is a tumor suppressor gene, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Most mutations in the RB1 gene prevent it from making any functional protein, so it is unable to effectively regulate cell division. As a result, cells divide uncontrollably and form a tumor.

A small percentage of retinoblastoma cases are caused by a deletion in the region of chromosome 13 that contains the RB1 gene. Geneticists refer to this region as 13q14. Children with these chromosomal deletions may also have intellectual disability, slow growth, and characteristic facial features (such as prominent eyebrows, a short nose with a broad nasal bridge, and ear abnormalities).

Read more about the RB1 gene and chromosome 13.

Mutations in the RB1 gene are inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to increase cancer risk. A person with retinoblastoma may inherit an altered copy of the gene from one parent, or the altered gene may be the result of a new mutation. For retinoblastoma to develop, a second mutation in the other copy of the RB1 gene must occur in retinal cells during the person's lifetime.

If there is a family history of the disease or if a person develops tumors in both eyes, the RB1 mutation is probably in all of the person's cells, including sperm or egg cells. This person is said to have the inherited form of retinoblastoma, and there is a risk of passing on the mutated RB1 gene to the next generation. However, if only one eye is affected and if there is no family history of the disorder, the RB1 gene may be mutated only in tumor cells. This person likely has the noninherited form of retinoblastoma, and there is no increased risk to other family members.

The small number of retinoblastoma cases caused by chromosome 13 deletions are usually not inherited. These chromosomal changes occur as random events during the formation of reproductive cells (eggs and sperm) or during cell division early in fetal development.