The Inheritance of Retinal Degenerations

Page 8

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The science of genetics is expanding rapidly. New techniques are available to locate disease-causing genes on each of the 23 pairs of chromosomes, to isolate and study these genes and to determine their mutations. Retinal degeneration researchers have already located and characterized some of the genes that cause these diseases and continually search for others.

In medicine, genetic research has the greatest impact so far in testing for retinal degenerations. As more retinal degeneration genes are identified, new gene-based tests are being developed. Genetic tests allow for faster and more accurate diagnosis.

Early discovery of a retinal degeneration can lead to earlier use of known treatments that may slow the disease. For example, if a doctor knows that a patient has an altered gene, he or she may suggest that the patient start taking vitamin A palmitate. If a child were at a significant risk for a retinal degeneration, earlier diagnosis of the condition could mean earlier interventions, such as evaluation of the benefit of low vision aids, school adaptations, or orientation and mobility training.

Although the use of genetic testing allows the diagnosis of these diseases, treatments that cure retinal degenerations are still not available. Continued genetic research will lead the way to future treatments, especially in the development of gene therapy for retinal diseases. Discovering the genetic causes of a disease is a crucial first step in developing means for prevention and cure.


Many people affected by retinal degenerative disease ask about genetic testing for themselves or their families. In some cases it is now possible to diagnose retinal degeneration through a gene test. Genes can be obtained from a blood or tissue sample. Researchers can separate DNA from the rest of the sample and test for the presence of disease-causing genes.

Once a gene has been located, it is possible, in certain families, to perform tests on the genetic material found in blood and other cells to determine which members of the family have a retinal degeneration gene. Two categories of tests are available for retinal degenerative diseases: direct testing and indirect testing. The results of direct and indirect genetic testing can be used to determine if an individual carries a gene (carrier detection), to predict the presence of disease before symptoms appear (presymptomatic diagnosis), or to find out if an unborn child will be affected later in life (prenatal diagnosis).

Direct Testing

Direct tests are much like any other medical blood tests in that they show whether or not a certain disease is present. A direct test requires that the gene and the specific mutation, the change that causes the disease, are known. Researchers can then look for the disease-causing mutation. If it is present, then the individual has the genetic disorder.

For example, mutations can be detected in any of 3 genes that cause autosomal dominant RP (ADRP) known to date. If an individual with ADRP has a mutation, other family members can be tested for that mutation. Family members who are found to have the same mutation are likely to have ADRP also. If the individual with ADRP does not have any of the known mutations, the individual and his or her family might want to pursue indirect gene testing.

Unaffected individuals with a family history of retinal degeneration and individuals who are affected but do not have a family history can also have direct tests for all the known gene mutations. However, if their tests were negative this does not guarantee that they do not carry a mutation, or will not pass it on to children. The genes known to date do not cover all cases. Scientists are still searching for more genes and mutations. In many cases, direct testing is possible for ADRP, Usher syndrome type I B, some macular dystrophies, choroideremia, and gyrate atrophy. Direct testing may take a period of weeks to be completed by the laboratory service.

Indirect Testing

Indirect tests take advantage of the fact that genes and other DNA regions that lie close together on the same chromosome are usually inherited together. In other words, these genes are "linked." To find the links between genes, scientists perform a specific type of study using markers. Markers are DNA fragments with harmless variations that are unique to families. Markers are not involved in causing disease themselves but might have a disease gene next to or sandwiched in-between them--they can act as "flags" for the area that contains a disease gene. If the disease gene is linked to a marker, scientists can detect where that gene is located.

Because all individuals inherit markers from both parents, researchers must compare markers from affected and unaffected individuals to sort out which ones are associated with the disease. Therefore, several family members are needed from more than one generation. The certainty of indirect testing results depends on how close the disease gene is linked to markers. Sometimes, markers cannot be readily identified and a disease gene cannot be traced through a family. Continued research and identification of new markers may be helpful in genetic diagnosis at a later time for these families. While direct testing may take a few weeks, indirect testing might take much longer. Most of the known retinal degeneration genes were found by linkage analysis.

Who Does Genetic Testing?

Because the development of genetic tests is still new, most of the laboratories testing for genes and mutations are full-time research laboratories, not fee-for-service diagnostic laboratories.

How Can I Have Genetic Testing?

Reports obtained from genetic testing are often difficult to interpret. That is why most researchers involved in genetic testing require that the individual or family interact with a local genetic or medical provider who will arrange for the testing, explain the results and address any concerns before or after testing. If you are interested in exploring genetic testing, the first step is to contact your ophthalmologist family doctor or genetic counselor (see below) Then, call the Information and Referral Office at The Foundation with the full name, address and phone number of your doctor or counselor. Foundation staff will send testing information to your provider. Costs for genetic counseling vary and are sometimes covered by health insurance. To answer questions about coverage, individuals must explore their own health insurance plans. Fees for genetic testing vary greatly; at this time most laboratories charge no or low fees.


Questions about your family's risks for developing a genetic disorder like retinal degeneration are best answered in a genetic counseling session. Genetic counseling can provide practical information to you and your family about the inheritance of genetic conditions. The process includes discussion of family history (and construction of a pedigree), available tests, treatments and research options; examination of medical records; and assessment of the chances that the disease might occur again in your family. Such counseling can be provided by an ophthalmologist or family doctor with special training in genetics. However, most certified genetic counselors are Masters degree-level health care professionals who have followed a specific educational course.

Who should consider genetic counseling?

Any person with an inherited retinal degenerative disease or with a family history of one of these diseases is a candidate for genetic counseling.

Why should you participate in genetic counseling?

You may choose to have genetic counseling:
1. to learn how the disease is inherited in your family and to learn about the chance of passing it to your children,
2. to learn more about presymptomatic diagnosis or carrier detection,
3. to learn more about prenatal diagnosis,
4. to learn about the latest advances in research and testing, and to determine if they are useful to your family.

When should I consider genetic counseling?

You should consider genetic counseling immediately after you or a family member are diagnosed with a retinal degenerative disease, before you marry, or before you have children. If you intend to use this information to plan a family, it is best to plan long in advance of any pregnancy.

How can I find a genetic counselor?

If you are interested in genetic counseling, the following can help you to identify an appropriate professional:
1. ask your ophthalmologist to refer you to an ophthalmologist trained in retinal diseases and/or genetics, to a medical geneticist or to a genetic counselor;
2. contact the departments of ophthalmology genetics obstetrics or pediatrics at the nearest university medical school or major hospital;
3. contact your state department of health and ask for genetic counseling referrals;
4. contact your local March of Dimes chapter (see the Resource List at the bottom of this page);
5. contact the National Society of Genetic Counselors (see Resource List at the bottom of this page);
consult one of The Foundation Research Centers; write or call The Foundation Fighting Blindness at the address and phone found in this booklet.


Alliance of Genetic Support Groups
35 Wisconsin Ave, South 440
Chevy Chase, MD 20815
(800) 336-4363

March of Dimes, National Office
1275 Mamaroneck Ave.
White Plains, NY 10605
(800) 367-6630

National Center for Education in
Maternal & Child Health

2000 15th Street North, Suite 701
Arlington, VA 22201-2617
(703) 524-7802
National Organization for Rare Disorders

P.O. Box 8923
New Fairfield, CT 06812
(800) 999-6673

National Society of Genetic Counselors
233 Canterbury Drive
Wallingford PA 19086-6617
(215) 872-7608

Foundation Fighting Blindness
Executive Plaza, Suite 800
11350 McCormick Road
Hunt Valley, MD 21031-1014
(800) 683-5555
(800) 683-5551 TDD

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Date last modified December 4, 1998