Carrier Inheritance

What is a Carrier?

A carrier is a person who ”carries” a genetic variant on one copy of a gene, while the other copy is as we would expect it to be. Carriers for many conditions do not have symptoms, but could pass the variant onto their children. Since the DMD gene is located on the X chromosome, and most females have two X chromosomes whereas most males have just one, females with one DMD variant may be called “carriers” while males with a DMD variant are expected to have a diagnosis of dystrophinopathy. It is important to note that with DMD variants and many other X-linked genes, carriers are at risk to have a child with dystrophinopathy, and are at risk to develop symptoms themselves. Carriers can have some symptoms of dystrophinopathy, such as muscle weakness and cardiomyopathy. All carriers should be evaluated by a healthcare provider familiar with Duchenne.

It is important to remember that dystrophinopathy is not always inherited from a mother who is a carrier. Approximately 70% (2 out of 3) of children born with Duchenne have inherited the genetic variant from their mother who is a carrier. However, approximately 30% (1 out of 3) of children born with Duchenne have a genetic change that started in them and was not inherited. This is called a “spontaneous” or a “de novo” variant. 

For Becker, the rate of a de novo variant is lower, approximately 10%, and the rate of inheriting the gene variant from their mother is higher, approximately 90%. This means that an individual diagnosed with Becker who has no known family history has a 90% chance of having a mother who is a carrier.

HOW IS DYSTROPHINOPATHY PASSED THROUGH CARRIERS?

This illustration shows how a variant that causes an X-linked disorder can pass from a carrier to her children. 

Each time a carrier has a son, there is a 50% chance (or 1 out of 2) that he will have dystrophinopathy, and each time a carrier has a daughter, there is a 50% chance (or 1 out of 2) that she will be a carrier. Carriers have no control over which copy of their X chromosome they pass on to their children.

HOW IS DYSTROPHINOPATHY PASSED THROUGH GERMLINE MOSAIC CARRIERS?

If you have a child with dystrophinopathy and you have had negative carrier testing, your doctor or genetic counselor may have mentioned the chance of germline mosaicism. Please read our section on Germline Mosaicism to learn more.

A WOMAN HAS A CHILD WITH DYSTROPHINOPATHY. HOW LIKELY IS IT THAT SHE IS A CARRIER?

• If a female has a child with dystrophinopathy and she has other affected male family members (such as an affected brother or nephew), it is extremely likely that she is a carrier.
• If a female has a child with Duchenne, and there are no other affected family members, there is approximately a 70% (⅔ or 2 in 3) chance that she is a carrier. Approximately 30% (⅓ or 1 in 3) of children born with Duchenne have a genetic change that started in them and was not inherited. This is called a “spontaneous” or a “de novo” variant. 
• If a female has a child with Becker, and there are no other affected family members, there is approximately a 90% chance that she is a carrier and a 10% chance that the gene variant started in their child with Becker.

The possibility for new variants is one of the reasons why 1/3 or more of individuals with Duchenne will have no family history. Another possibility is that some families have several generations with mostly or all females, and few or no males to present with Duchenne or Becker. These families may not know that there are several generations of carriers.

WHAT IS THE CHANCE OF DYSTROPHINOPATHY HAPPENING AGAIN IN A FAMILY?

• If a woman is a carrier, each time a carrier has a son, there is a 50% chance (or 1 out of 2) that he will be affected with Duchenne or Becker, and each time a carrier has a daughter, there is a 50% chance (or 1 out of 2) that she will also be a carrier.
• If a woman has a son with Duchenne or Becker but her carrier testing was negative, she should be told about the chance of germline mosaicism. It is not known exactly how often germline mosaicism occurs in women with negative carrier testing, though some studies have suggested up to an 11% chance to have a second child affected. Learn more about germline mosaicism.

Once dystrophinopathy has been diagnosed in a family, it is important for family members to talk with a genetic counselor. A genetic counselor will take a detailed family history and will determine who else in the family may need genetic testing. Learn more about genetic counseling.

The only way to know for sure if a female is a carrier is by genetic testing. However, carrier testing is much more accurate if the variant is first confirmed in an affected relative. If you have a relative who needs genetic testing for dystrophinopathy, please refer them to our Decode Duchenne program, which provides free genetic testing for individuals with dystrophinopathy and their family members. Learn more about carrier testing.