Retinitis pigmentosa

Inheritance

How is retinitis pigmentosa inherited?

Retinitis pigmentosa is a term that describes a group of inherited progressive retinal diseases. As of October 2016, all forms of retinitis pigmentosa are thought to be caused by genetic changes. This may or may not mean that the gene changes were inherited. There are a subset of cases of retinitis pigmentosa that are known to be "simplex". Simplex cases of retinitis pigmentosa are those that are the first and only known occurrence within a family. Even within simplex cases, however, a genetic cause is often identified and or assumed to be the cause. It should be noted that there are some vision disorders that can mimic some of the symptoms of retinitis pigmentosa that are not inherited. For example, certain toxic drug reactions, eye disturbances due to syphilis, infections, complications secondary to cancer, and ophthalmic artery blockages can cause vision loss similar to that experienced in retinitis pigmentosa. These can be readily differentiated from retinitis pigmentosa after evaluation by a specialist.

Over 60 forms of nonsyndromic retinitis pigmentosa have been identified and dozens of genes associated with this condition. The different forms of nonsyndromic retinitis pigmentosa can be inherited in basically every manner in which diseases are known to be inherited: autosomal recessive (5-20% of cases), autosomal dominant (15-25% of cases), X-linked (5-15% of cases), mitochondrial (rare), and digenic (also rare). It should also be noted that 10-50% of cases are known to be simplex, and the underlying genetic cause in these cases is often unknown, making the form of inheritance in these cases uncertain.

Forms of inheritance:

  • Autosomal recessive: in this form of inheritance the gene change is present on one of the first 22 pairs of chromosomes, which are referred to as autosomes. "Recessive" means that in order to have the disease, both copies of the gene are abnormal, or changed. One each of the pair of abnormal genes are typically inherited from both of an affected individual's parents. The parents, being unaffected carriers of the condition, do not display signs of retinitis pigmentosa themselves. For this reason, cases of autosomal recessive retinitis pigmentosa typically "pop up" in the family, seemingly from nowhere. Many cases of simplex retinitis pigmentosa may be due to autosomal recessive gene changes that have not yet been identified.
  • Autosomal dominant: this form of inheritance also involves a gene change on one of the autosomes. "Dominant" means that the gene change must be present on only one of the two copies of the gene in order to cause in the condition. When a parent has autosomal dominant retinitis pigmentosa, each of their offspring are at 50% risk to inherit the gene and also be affected. Although most people with autosomal dominant retinitis pigmentosa have an affected parents, it is possible for two unaffected parents to have a child with autosomal dominant retinitis pigmentosa if a spontaneous gene change, known as a "de novo" change, occurs in the copy of the gene in the egg or sperm cell.
  • X-linked: in this form of inheritance the gene change is present on the X chromosome, one of the 23rd pair of chromosomes that determines gender. In the X-linked forms of retinitis pigmentosa, females who carry the gene changes may not manifest any signs of the disease. Those that do, about 20% of carrier females, are typically more mildly affected than males in the same family. The offspring of a mother with X-linked retinitis pigmentosa are each at 50% risk to inherit the gene, with male offspring being more likely to be more severely affected than their sisters. Only the daughters of a male with X-linked retinitis pigmentosa can inherit the gene for the condition, as men pass a Y chromosome, not an X, to their sons. Therefore, a hallmark of X-linked inheritance is that there is no transmission of the disease from father to son.
  • Mitochondrial: in this form of inheritance, the changed gene is located on DNA housed within a structure in cells known as mitochondria. Mitochondria have their own set of DNA which is separate from the standard, "nuclear" DNA. Mitochondrial DNA, unlike nuclear DNA, is inherited from the mother only. The severity of the disease depends on the percentage of abnormal mitochondrial DNA which a person inherits. This can vary from sibling to sibling.
  • Digenic: in this form of inheritance, changes in two separate genes are required to develop the associated disease. This is a rare cause of retinitis pigmentosa.

To discuss how retinitis pigmentosa runs in families as well as risks for particular family members, or your future offspring, to develop this condition, you can contact a genetic counselor. To find a genetic counselor in your area, go to the search page on the National Society of Genetic Counselors website.

Show More Content Like This

More Inheritance Content

What does it mean to have inherited a "variant" or "variant of unknown significance" in a gene associated with retinitis pigmentosa?

Are there forms of retinitis pigmentosa that aren't genetic?

What does it mean to have inherited a "variant" or "variant of unknown significance" in a gene associated with retinitis pigmentosa?

Although the diagnosis of retinitis pigmentosa can be made clinically based on visual examination and history without genetic testing, genetic testing can be used to confirm the diagnosis in an individual with symptoms suspicious for the disorder. Many individuals with a clinical diagnosis of retinitis pigmentosa have no genetic change identifiable by current genetic testing methodologies. A smaller number of affected individuals are found to have a change in the spelling of one of the genes associated with retinitis pigmentosa, but it is unknown whether the specific gene change found would cause disease, and so the genetic test result is not conclusive. This is known as a "variant of unknown significance".

We all have differences in the way our genes are spelled (gene variants). In many cases, these spelling changes do not appear to change the protein that the gene produces and therefore do not seem to lead to any health or developmental problems. Some changes, though, can alter the way a gene works, leading to an abnormal protein product being made. When this happens, a disease can occur. There are several changes that have been identified in the 50+ genes associated with retinitis pigmentosa that are known to cause the disorder. In other cases, however, a variant of unknown significance is found, the effect of which, if any, is unknown.

When a person who is suspected to have retinitis pigmentosa has genetic testing and a variant in one of those genes is found, we can not be sure whether that gene change is the cause of the symptoms that person has. If the person had enough symptoms to allow for the diagnosis of retinitis pigmentosa to be made clinically, the finding of a variant will likely not lead to the doctor changing or removing the diagnosis. Over time, as more people have genetic testing for the condition, unclear gene variants may be reclassified as disease-causing if identified in enough affected individuals, or benign if identified in enough unaffected individuals.

It is also possible that a person with signs of retinitis pigmentosa but with only a variant identified on genetic testing may have a change or changes in other genes that have not yet been identified as being associated with the disease. Over time, we may identify more genes that cause retinitis pigmentosa, leading to more extensive genetic testing for this condition to be possible.

If you have questions about what it means to have a variant of unknown significance in a gene associated with retinitis pigmentosa, talk to your doctor or contact a genetic counselor. To find a genetic counselor in your area, go to the search page on the National Society of Genetic Counselors website.

Are there forms of retinitis pigmentosa that aren't genetic?

As of October 2016, all forms of retinitis pigmentosa are thought to be caused by genetic changes. Nonetheless, there are some vision disorders that can mimic some of the symptoms of retinitis pigmentosa that are not inherited. For example, certain toxic drug reactions, eye disturbances due to syphilis, infections, complications secondary to cancer, and ophthalmic artery blockages can cause vision loss similar to that experienced in retinitis pigmentosa. These can be readily differentiated from retinitis pigmentosa after evaluation by a specialist. An ophthalmologist is a specialist who can typically perform these evaluations. If you have questions about this, talk to your doctor about being evaluated or being referred to a specialist.

We use cookies to ensure that we give you the best experience on our website. By continuing to browse this site, you are agreeing to our use of cookies.

Continue Find out more about our use of cookies and similar technology

This content comes from a hidden element on this page.

The inline option preserves bound JavaScript events and changes, and it puts the content back where it came from when it is closed.

Remember Me