DuchenneConnect Advice about Genetic Testing

We get many questions about genetic testing.  Some of the most common questions are listed below.  Choose any of the questions to see what the testing plan we recommend.  If you have questions that are not answered in the information below, visit the DuchenneConnect registry to create a profile, and then contact us.

My child is suspected to have DMD/BMD, and no one else in our family has muscular dystrophy. My child has not had genetic testing or a muscle biopsy. What do we do now?

If he/she has not already done so, your doctor will most likely order CPK (creatine phosphokinase) blood testing as a first step in the diagnostic process. Your doctor will then order genetic testing to confirm the diagnosis. In rare cases, a muscle biopsy may be necessary. DuchenneConnect suggests the following logical testing process for obtaining a diagnosis of Duchenne or Becker muscular dystrophy.

Step 1. Use a blood sample to test for large deletions and duplications to the Glossary Link gene

Your healthcare provider should consider beginning with a Glossary Link DNA testing method that detects large deletions and duplications of one or more exons in the dystrophin gene.

Step 2. Use a blood sample to test for small changes to the gene using gene sequencing

If no deletion or duplication is identified after step 1, you and your healthcare provider may want to use gene sequencing as a follow-up testing method. Your provider should look for laboratories offering full gene sequencing (Sanger sequencing) or re-sequencing array technologies.

Step 3. Muscle biopsy and biochemical testing

If no Glossary Link mutation is found after genetic testing (using very informative testing strategies like steps 1 and 2 above), you and your healthcare provider may want to use muscle biopsy and biochemical testing. Your provider should specifically order immunostaining (looks at the presence of the dystrophin Glossary Link protein) as well as immunoblot, also known as Western blot (looks at the size, amount, and quality of the protein).

If I have had a muscle biopsy, do I need genetic testing?

A muscle biopsy that shows a smaller amount or complete lack of dystrophin protein can confirm a diagnosis of Duchenne or Becker muscular dystrophy. Genetic testing offers benefits beyond diagnosis, however, and many families choose to have genetic testing after a diagnostic muscle biopsy. Benefits of genetic testing after a diagnostic muscle biopsy include:

Family planning: Knowing the genetic mutation in your family allows for more informed reproductive planning. Once the genetic mutation is found, women in your family may choose to have Glossary Link carrier testing so that they know the chance of having a (or another) child with Duchenne or Becker muscular dystrophy. Some carriers choose to have Glossary Link prenatal testing. Others may consider reproductive techniques that can increase the chances of having female children. Some families choose adoption. Other women decide that their carrier status will not change their reproductive plans.

Participation in research studies: Some clinical treatment studies will require that you have a known genetic mutation to be in a study. For example, studies that are attempting to correct the gene change in some way (for example, exon skipping or PTC124) require a known mutation for participation.

Clarifying relationships between the genetic mutation and progression of the disorder: As more people with Duchenne and Becker muscular dystrophy have genetic testing, researchers will have more data that will allow them to figure out the relationship between different types of gene changes and the disorder outcome.

If a you or a relative had a muscle biopsy and tissue is still available, you can use a testing method called cDNA to look for mutations in tissue from the muscle biopsy.

If I had genetic testing in the past and no mutation was found, should I be retested?

You should discuss your results with a genetics professional or the neuromuscular clinic that provides your care. Genetic testing methods have changed a lot since the first genetic testing was offered in the late 1980s. It is possible that a mutation could be detected today that was not found by earlier testing methods.

If I had genetic testing in the past and a mutation was found, do I need to do any more genetic testing?

You should discuss your results with a genetics professional or the neuromuscular clinic that provides your care. It may or may not be worthwhile to have more genetic testing. 

Single base pair mutations (replacement of one base for another) and small insertions or deletions found by sequencing are not expected to change and more genetic testing is probably not needed.

If past testing found a large deletion of one or more exons, re-testing may provide more information about the exons involved in your deletion.

This is because for many years deletion testing looked only for changes in the 18 most commonly deleted exons (referred to as the Beggs and Chamberlain sets). If a deletion went beyond these exons, it may not have been accurately reported. For example, exons 50, 51, 52, and 60 were routinely tested. If a deletion spanned exons 50-55 this would likely have been reported as a deletion of 50-52. Knowing the true size of the deletion probably won’t change carrier testing or reproductive options, but may help us learn more about the relationship between specific mutations and disorder progression, and may affect your eligibility for research studies.

Should I have genetic testing if I am an adult female with a relative with Duchenne or Becker muscular dystrophy, but no affected children?

In this case, carrier testing will help you know if you are a carrier and the chance that you could have a child with Duchenne or Becker muscular dystrophy. Carrier testing is disease specific. Females who may be carriers should only be tested for the condition in their family. If you do not know what type of muscular dystrophy is in your family, you should try to get medical records on your affected family member and share that information with a healthcare provider familiar with muscular dystrophy. If the specific type of muscular dystrophy can be found in the medical records, or through blood or muscle samples that may have been stored on the affected family member, genetic testing may be able to determine your carrier status.

If you are found to be a carrier

If you are found to be a carrier, you should have your heart checked. Carriers have an increased chance for changes in heart function. Prenatal testing and other reproductive options are available for carriers who are interested in such testing. Other women may choose to proceed without reproductive options, understanding the chance. Some women decide to adopt. See the section on “Information for Carriers, Potential Carriers, and Mothers of Affected Children” to learn more.

Should I have genetic testing if I am an adult female with a child with Duchenne or Becker muscular dystrophy?

Any woman with a child Duchenne or Becker muscular dystrophy should be offered carrier testing for 3 reasons:

  1. Carriers for Duchenne and Becker muscular dystrophy are at increased risk of changes to heart function, and carriers should have a cardiac evaluation. 
  2. Carrier testing may help women make reproductive plans because the testing provides information about the chance for muscular dystrophy to happen again. Prenatal testing and other reproductive options are available for carriers who are interested in such testing. Other women may choose to proceed without reproductive options, understanding the chance to have an affected child. Some women decide to adopt. 
  3. Carrier testing for the mother of an affected child will help clarify whether other females in the family may be at risk to be a carrier for Duchenne or Becker muscular dystrophy.

If you have a child with DMD or BMD and you have other affected male family members, for example an affected brother or nephew, it is extremely likely that you are a carrier.

If you have no other affected family members, there is a 66% (or 2 in 3) chance that you are a carrier. Approximately 33% (or 1 in 3) of cases of Duchenne muscular dystrophy are caused by what are called new mutations. These are random changes to the genetic code in the dystrophin gene that happen in only one egg or sperm. That one egg or sperm could create an affected male; rarely, an affected female; or a carrier female child who could later have affected children.

The possibility for new mutations is one of the reasons why 1/3 or more of individuals with Duchenne muscular dystrophy will have no family history. Another possibility is that some families have several generations with mostly or all females (that is, they have no boys to express the disease). These families may not know that there are several generations of carriers. See the section on “Information for Carriers, Potential Carriers, and Mothers of Affected Children” to learn more.

The DuchenneConnect Coordinator can help you and your healthcare provider evaluate a genetic testing strategy or your past genetic testing. To contact the Connect Coordinator, visit the DuchenneConnect registry to create a profile, and then contact us.