Duchenne Muscular Dystrophy Genetic Testing

Duchenne Muscular Dystrophy Genetic Testing

Duchenne Muscular Dystrophy

What is Duchenne muscular dystrophy?
Muscular dystrophy refers to a group of disorders characterized by muscle weakness. In Duchenne dystrophy, a defective gene causes muscles to produce abnormally low levels of a protein called dystrophin. When dystrophin levels are low, the membranes around muscle cells become weak and tear easily, eventually leading to the death of muscle fibers.

Duchenne muscular dystrophy is the most common form affecting children, mostly boys. Symptoms usually begin during the toddler or preschool years (around ages 2 to 6). The muscle weakness affects many muscles, including those in the trunk and hips. The trunk muscles can become so weak that the spine curves, creating a condition known as scoliosis. Weakness also affects muscles of the arms and legs, the heart muscle and the diaphragm muscle. Children with Duchenne muscular dystrophy will need a wheelchair by the time they are teen-agers. Weakness of the heart muscle, called cardiomyopathy, occurs by age 18 in 100 percent of people with Duchenne muscular dystrophy. Life expectancy depends on how quickly and intensely the disease progresses and on how it affects the ability to breathe. The average lifespan is less than 30 years.

How common is Duchenne muscular dystrophy?
About one out of every 3,500 boys is born with the mutation for Duchenne muscular dystrophy. In about two-thirds of cases, a child inherits the gene from his mother. A new mutation in the child accounts for the other one-third of cases.

Who is at risk for Duchenne muscular dystrophy?
Every couple has a potential risk of having a boy with Duchenne. No particular group of people has higher rates of being carriers. Family history is the only determining factor.

Is there a cure?
There is no cure for muscular dystrophy, but there are some guidelines for treatment of the symptoms. The best treatments prolong survival and improve a person’s quality of life. For example:

  • Physical therapy helps to prevent stiff muscles.
  • Monitoring for scoliosis allows for early treatment. (Untreated scoliosis can hamper breathing.)
  • Regular monitoring of the heart (with echocardiograms) allows early detection and treatment of cardiomyopathy. Early treatment of heart problems can result in improved heart function.
  • Attention to diet helps to control the patient’s weight.
  • A type of steroid may help improve muscle strength.
  • There are also guidelines for special precautions to be taken when a patient with Duchenne dystrophy needs anesthesia or sedation.

The Gene For Duchenne Muscular Dystrophy

What does it mean to have an altered gene for Duchenne?
The gene involved in Duchenne muscular dystrophy tells the body how to make a protein called dystrophin. This protein is important in maintaining healthy muscle cells. Seventy percent of Duchenne muscular dystrophy cases have a large part of the gene missing, which means the muscle cells are unable to make dystrophin. The muscle fibers die, causing the entire muscle to become weak and ineffective.

The Duchenne muscular dystrophy gene is located on the X chromosome. Every male child inherits an X chromosome from his mother and a Y chromosome from his father. Female children get two X chromosomes, one from each parent. If there’s a change in an X-chromosome gene, the typical female has a second X chromosome that almost always carries a normal version of the gene. Males, on the other hand, do not have a second X chromosome. As a result, girls almost never get Duchenne. If a boy has a changed gene, he will automatically get the disease.

Should You Be Tested?

Should you or your future child be tested for Duchenne?
That depends on whether you are a likely to be a carrier of the disease. Your chances of being a Duchenne muscular dystrophy carrier partly depend on your family history. If you are the mother of a boy with this disease and you have another family member with the disease, such as a brother or a nephew, you must be a carrier. If you are the mother of a boy with the disease, but nobody else in your family has it, you still may be a carrier. (About two-thirds of mothers in this situation turn out to be carriers due to the high rate of new mutations.) The only way to learn if you are a carrier is by getting a DNA test. If you are a carrier, you also should have an echocardiogram to look for cardiomyopathy.

Should your child be tested for Duchenne if symptoms exist?
Symptoms of Duchenne muscular dystrophy usually start during the toddler years (ages 2 to 6). An affected child usually will start walking later than expected, have difficulty walking up stairs, walk with flat feet or on the toes. There are different kinds of tests to look for Duchenne. All people with Duchenne muscular dystrophy have high levels of a muscle enzyme called creatine kinase. Therefore, if your child has symptoms of the disease, the first step is the creatine kinase test, as well as some other types of blood tests. DNA testing can be used to confirm a diagnosis in a child who has symptoms.

Understanding Test Results and Options

How Do You Make Sense Of The Results?

If I test positive as a carrier, what does that mean for my family and me?
A DNA test can confirm that you are a carrier for Duchenne muscular dystrophy. If you are a carrier, you will not have the disease. However, you may have some of the symptoms. The most common symptoms among carriers are muscle weakness and muscle pain or cramping. Note: Cardiomyopathy can affect all Duchenne carriers, so it is important to get an echocardiogram even if you are not experiencing symptoms.

If a DNA change is identified in one family member, then other family members can be tested for the same change. In other words, if you are a carrier and your mother was a carrier, each of your sisters has a 50-percent chance of having inherited the gene. Your sisters may want to be tested before they start families.

If my child tests positive, what does that mean for my family and me?
If your child has symptoms of Duchenne muscular dystrophy, and his creatine kinase is high, your doctor should get a DNA test to confirm the diagnosis. If the child has a change in the Duchenne muscular dystrophy gene, the mother should be tested to see if she is a carrier.

Does anyone ever get a positive test result, but not get the disease (a “false” positive)?
Changes to the Duchenne muscular dystrophy gene can cause two other types of muscular dystrophy. In Becker muscular dystrophy, symptoms start later and progress more slowly. The other type of muscular dystrophy is X-linked dilated cardiomyopathy, which is limited to the heart muscle.

Does anyone ever get a negative test result, but actually have a mutation in the gene (a “false” negative)?
Yes. About 30 percent of people with Duchenne muscular dystrophy will get a negative result with the standard test for deletions. Because the Duchenne muscular dystrophy gene is very large, it has been difficult to test every single part of the gene. A deletion test is done first because it is easier to do. If the deletion test is unsuccessful, your doctor may suggest a different DNA test to look for small changes in the gene. However, even the second DNA test sometimes fails to find any change. But after doing both types of DNA tests, a change will be found in about 90 percent of people with Duchenne muscular dystrophy. This makes the false-negative rate about 10 percent.

When DNA testing fails to detect the Duchenne muscular dystrophy gene in a boy with symptoms of the disease, a muscle biopsy can confirm the diagnosis. A very small piece of the thigh muscle is removed and examined for the presence of the dystrophin protein. A muscle biopsy used to be required to diagnose Duchenne muscular dystrophy, but due to the success of DNA testing, a biopsy is now required in only a minority of cases.

Personal Questions

If I have the Duchenne gene, can I have children who don’t have it?
If you’re a Duchenne muscular dystrophy carrier (and remember, men can’t be carriers), you have a 50-percent chance of passing the gene on to each child you have. Boys who inherit the gene will develop Duchenne muscular dystrophy. All girls who inherit the gene will be carriers.

While I’m pregnant, can I determine the risk my baby has of developing Duchenne?
To discover whether your unborn child has inherited Duchenne muscular dystrophy, you and your partner can get prenatal testing. Prenatal DNA testing is only performed if someone in your family has the gene or is known to be a carrier. Early in the pregnancy, a doctor can use either chorionic villus sampling or amniocentesis to get a sample of tissue from the fetus. A lab then tests the tissue sample to determine if the fetus has inherited the disease.

If you are using in vitro fertilization, you may be able to have the embryo examined right after the egg and sperm are combined and before the resulting embryo is implanted in the womb.

Be sure to talk with your obstetrician or a genetic counselor about your options.

If I am a Duchenne carrier, could I give birth to a girl with the disease?
In rare cases, a girl can get Duchenne muscular dystrophy. However, this only occurs in conjunction with some other problem in the inheritance of the X chromosomes. So, a muscular dystrophy specialist should evaluate any girl with symptoms of Duchenne muscular dystrophy.

If I DON’T have the Duchenne gene, can I have children who DO have the gene?
If you’re not a carrier, then your children cannot inherit the gene from you. But there is a relatively high occurrence of new changes in the Duchenne gene. Because of this, there is no guarantee that you won’t have a child with Duchenne muscular dystrophy.

Is there any harm in finding out if I carry the gene?
Carrying the gene can cause medical problems for some women. The most significant problem for women who carry a Duchenne muscular dystrophy mutation is dilated cardiomyopathy. A standard echocardiogram can detect this complication. Early detection helps to prevent later complications.

Test Details

How does the test work?
There are two types of DNA tests for Duchenne muscular dystrophy:

  1. Deletion testing looks for large deletions and duplications in the gene. This test reveals the genetic change responsible for the disorder in about 70 percent of patients with Duchenne muscular dystrophy.
  2. Point-mutation testing detects smaller changes than the ones found by the deletion test, such as small insertions, deletions and point mutations.

Some patients with symptoms of Duchenne have normal genetic testing. A muscle biopsy will clarify the diagnosis in patients with symptoms, but who have received a normal DNA test. Muscle biopsy also helps when the symptoms are not classical but some type of change is found. The muscle is examined under a microscope and a special stain is used to detect dystrophin protein.

What is the cost of the test?
Cost varies slightly depending upon which lab is doing the testing. The DNA deletion test costs about $500. The DNA point-mutation test costs over $1,000. The special stain for dystrophin in the muscle biopsy costs about $800.

Does insurance pay for the test?
Most health-insurance companies will pay 80 percent or more of the cost of the test. Some companies pay all of the cost; others won’t pay any portion. If you are considering this test, call your insurance company and ask about its coverage.

How long does it take to get results?
Once you have blood drawn for the deletion test, you will receive the results in 2 to 3 weeks. Results for the point-mutation test take 6 to 8 weeks. Staining for dystrophin protein in the muscle biopsy takes 1 to 2 weeks. The test results will not be reported directly to you. Instead, the laboratory provides the results to the medical center that ordered the test. You would then return to the center for another appointment to discuss the results.

Can a health-insurance company raise my rates or drop me from coverage if I test positive?
In 2008, the U.S. government passed a law called GINA (Genetic Information Nondiscrimination Act). This law prohibits discrimination by health insurers and employers on the basis of genetic information. Learn more here.

The Federal Health Insurance Portability and Accountability Act (HIPAA) of 1996 also prohibits health-insurance discrimination based on any “health status-related factor,” (including genetic information) by group health plans. People with group insurance are usually covered by HIPAA, while people who are self-employed are covered only by state laws.

Some states have enacted legislation to cover the gaps. Thirty-four states prohibit health-insurance companies from using genetic information to deny coverage. Other states require specific justification for the use of genetic information in denying a claim.

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