Retinoblastoma: Causes and Risk Factors

What causes this rare eye cancer?

Table of Contents
View All
Table of Contents

Retinoblastoma is a rare form of eye cancer that is almost always diagnosed in children under the age of 5. Doctors are not always able to pinpoint or risk factors of retinoblastoma, but there are known genetic biomarkers that can cause this disease.

Research is still underway to understand the process that induces tumor growth in retinoblastoma. Patients and caregivers can learn a lot about the pathology (medical causes and effects) of their disease from laboratory results.

Lab worker putting medical blood sample in place after examining for sediments

sukanya sitthikongsak / Getty Images

Where Retinoblastoma Occurs

Retinoblastoma begins at the back of the eye, in the retina, a thin, light-sensitive layer of tissue, and continues to grow from there.

White pupil, or leukocoria, is caused by light reflecting against the tumor's white surface as it grows.

Crossed eyes (strabismus), bulging eyeballs (proptosis) or enlargement of the eyeball (buphthalmos), and an accumulation of inflammatory cells (hypopyon) are all caused by the growing tumor as it crowds out and dislodges parts of the eye.

When trying to make sense of a retinoblastoma diagnosis, it can be helpful to fully understand the anatomy of the eye.

What Causes Retinoblastoma?

Retinoblastoma is almost always genetic, whether inherited (passed on from parent to child) or spontaneous (occurring without outside influence). Researchers are still exploring what prompts nerve cells to mutate into this rare form of eye cancer, but doctors know that it is most likely set in motion by a random error in gene transcription (the development of genes) that generates faulty instructions within cells.

When that genetic error occurs, DNA in cells of the eye becomes corrupted. This causes cells to grow out of control, creating a mass, or tumor. In addition, while healthy cells are born and die to make room for new cells, cancer cells have been deprogrammed from dying. This further contributes to out of control growth and spread (metastasis).

Does Retinoblastoma Occur in Adults?

Retinoblastoma is so incredibly rare in adults that statistics are scarce. With inherited mutations, scientists believe that the patient may have gone into remission years ago from undetected childhood retinoblastoma that has now resurfaced. In these cases, the original tumor is called retinocytoma or retinoma.

RB1 Gene Mutation

Scientists have identified an RB1 gene mutation as one of the primary causes of retinoblastoma. In fact, mutations in RB1 cause most retinoblastoma cases. Doctors rarely identify mutations in other genes in patients with retinoblastoma. In a very small number of cases, the retinoblastoma is caused by mutations in the MYCN gene instead of RB1. Even more rarely, doctors find no genetic mutation at all and can not identify any causes.

There is a relationship between how the mutation occurs (inherited vs. spontaneous) and where it occurs (in one eye, in both eyes, and in the pineal gland, a small endocrine gland in the brain). Here is an overview;

  • Unilateral (occurrence in one eye): In nearly 85% of children who have retinoblastoma in only one eye (unilateral), a genetic alteration, called a germline mutation, has occurred spontaneously. This means that doctors do not know why it suddenly appeared (it is not inherited from a parent) and caused cancer.
  • Bilateral (occurrence in both eyes): In the other 15% of cases, in which retinoblastoma is in both eyes (bilateral), the genetic mutation has been passed down from parent to child, leading to tumor growth. Even if the parent never actually developed retinoblastoma themselves, they have passed down the predisposition (the likelihood that the disease will develop) to their children in these cases. 
  • Trilateral (occurrence in both eyes and pineal gland): A third type of the disease, trilateral retinoblastoma, starts in the pineal gland and then develops in both eyes as well. Trilateral retinoblastoma is always inherited from one or both parents.

How Mutations Affect the Cells

Whether they have it in one eye or both, one-third of people with retinoblastoma have inherited a gene mutation. Among those with the inherited form of retinoblastoma, the RB1 mutation is in every cell of their bodies. Of the other two-thirds whose mutation developed spontaneously, most have the RB1 gene mutation only in some, but not all, of their cells.

Risk Factors

No other retinoblastoma causes have been identified outside of genetic mutations, and scientists have not yet proven that there are any environmental or lifestyle factors that can cause it. Research into suspected risk factors is ongoing.

The only known risk factor for retinoblastoma, other than inheriting the mutation, is a very young age. Most children diagnosed with retinoblastoma are under the age of 5 years, and many are even infants. Children of all races develop retinoblastoma at near-equal rates, though children living in underserved communities tend to have worse outcomes of the disease because of healthcare limitations.

Scientists are still studying whether other factors might increase the risk for retinoblastoma. Among those factors actively suspected and being researched are:

  • Older age of the father at child's birth (there is a greater risk of genetic damage to sperm with advancing age)
  • Father's previous exposure to radiation
  • Mother's exposure to gasoline or diesel exhaust during pregnancy
  • A maternal diet low in fruits and vegetables during pregnancy

Risks Are Not Causes

It is important to remember that even if scientists prove that these factors increase the risk of a child developing retinoblastoma, a risk factor is not a cause. It simply makes it slightly more likely that a child will develop the disease.

Scientists believe that retinoblastoma causes are by and large random and often unpredictable. Once parents receive a diagnosis of retinoblastoma, it is most important to focus on understanding the disease and its treatment.

Summary

Retinoblastoma is a rare form of eye cancer that begins in the retina. It is mostly diagnosed in children under the age of 5 . Retinoblastoma is caused by a genetic mutation that can either be inherited or spontaneous. Scientists have identified an RB1 gene mutation as one of the primary causes of retinoblastoma, but other genetic mutations are possible.

Other than age, there are no known lifestyle risk factors that contribute to the development of retinoblastoma.

A Word From Verywell

People often want to know what causes a disease, what they could have done to prevent it, and how to prevent it in other family members. It is important for parents not to blame themselves for a genetic anomaly. Understanding the causes is important since genetic testing can let you know whether your child's disease is unilateral or bilateral and the other eye is at risk. It can also reveal whether other family members could be at risk.

A cancer diagnosis can cause a lot of stress for a family. Self-care is so important for both parent and child. This could be in the form of meditation, a support group, or getting out with friends to decompress.

Frequently Asked Questions

  • What is retinoblastoma?

    Retinoblastoma is a rare cancer that begins in the eye's retina, a thin layer of tissue at the back of the eye that helps process light. Of those children diagnosed with the disease, 1 in 4 have it in both eyes, and 3 out of 4 develop the cancer in one eye.

  • What causes retinoblastoma?

    Retinoblastoma is caused by a mutation in a gene that is involved in eye development. It can run in families, in which a child inherits the mutation from a parent who may or may not have had the disease themselves. It can also appear spontaneously.

  • Can retinoblastoma be prevented?

    Currently, doctors do not know of any way to prevent retinoblastoma, but early detection and treatment can greatly improve the prognosis.

  • Are there risk factors for retinoblastoma?

    Aside from age (under 5 years old) or an inherited mutation, scientists have not proven that there are risk factors for developing retinoblastoma.

  • What causes retinoblastoma to spread?

    Left untreated, retinoblastoma cells will continue to reproduce and will almost certainly spread to the other eye or other parts of the body, making it much harder to treat. If you detect any white in the pupil, eyes that appear crossed, a lazy eye, eye discomfort, or any visual disturbances, schedule an eye exam right away so that you can catch and treat the disease as early as possible.


5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cleveland Clinic. Retinoblastoma (cancer of the eye).

  2. Sengupta S, Pan U, Khetan V. Adult onset retinoblastomaIndian J Ophthalmol. 2016;64(7):485-491. doi:10.4103/0301-4738.190099

  3. Zugbi S, Ganiewich D, Bhattacharyya A, et al. Clinical, genomic, and pharmacological Study of MYCN-amplified RB1 wild-type metastatic retinoblastomaCancers (Basel). 2020;12(9):2714. doi:10.3390/cancers12092714

  4. Pandey AN. Retinoblastoma: An overview. Saudi J Ophthalmol, 2014;28(4):310-315. doi:10.1016/j.sjopt.2013.11.001.

  5. American Cancer Society. Risk factors for retinoblastoma.

By Jennifer Leavitt
Jennifer Leavitt, MS, is a health advocate, award-winning writer, and editor who empowers readers with evidence-based information.