For Carriers

What is a Carrier?

Historically, the word carrier referred to someone who has a genetic variant that cannot affect their health, but could be passed on to a child who develops symptoms. Women with two X chromosomes (referred to as “females” on these pages) and a single DMD gene variant are referred to as carriers because it used to be assumed that a woman with a DMD variant would never develop symptoms.

Now we know that carriers do sometimes develop symptoms, such as muscle weakness and heart problems. Though it is rare, some females even have the classic symptoms of Duchenne or Becker. Carriers with symptoms are often referred to as manifesting carriers or females with dystrophinopathy, although the language continues to evolve as we learn more about what it means to be a carrier. Dystrophinopathy is an umbrella term that refers to any health condition caused by DMD gene variants, including Duchenne, Becker, or milder symptoms. Carriers have an increased chance of having children with dystrophinopathy. All carriers should be evaluated by a healthcare provider familiar with dystrophinopathy. 

A carrier can:

• have a child or children with dystrophinopathy
• have family members with dystrophinopathy
• have symptoms of dystrophinopathy
• have no family history of dystrophinopathy and no symptoms of dystrophinopathy

It is important to remember that dystrophinopathy is not always inherited from a carrier mother. For example, about 70% (2 out of 3) of children born with Duchenne inherited the gene variant from their mother who is a carrier. However, about 30% of children born with Duchenne have a new gene variant that happened randomly and was not inherited. This is called a “spontaneous variant” or a “de novo” variant. The mother of a child with a spontaneous variant but no variant herself is not described as a carrier.

Why do carriers sometimes develop symptoms?

Scientists aren’t sure why some carriers have symptoms and some do not. While there are tests to see if a female is a carrier of a dystrophinopathy variant, there are no tests that can show for certain if a female will develop symptoms. 

In order to understand why some females have symptoms of dystrophinopathy while others do not, it is helpful to understand some background information about chromosomes. Chromosomes contain our genes and are the unit of DNA that is passed from parents to their children. Most males are born with one X chromosome (from their mother) and one Y chromosome (from their father). Because males typically only have one X chromosome, if the X chromosome they receive has a DMD gene variant, they will be affected with dystrophinopathy.

Females are born with two X chromosomes (one from their mother and one from their father), but in most cells of the body, only one X chromosome is “turned on” or active. One theory for why some females develop symptoms is that in their muscle or heart cells, the X chromosome with the “working” DMD gene is the one that is mostly turned off. This would leave the cells relying on the copy with the gene variant, making symptoms more likely. On the other hand, if most of a female’s muscle and heart cells turn off the X chromosome with the DMD variant, she may have few or no symptoms. Currently, there is no easy way to test which X chromosome is turned on in someone’s cells (called X-inactivation studies), so it’s important for all carriers to get regular screening to check for any signs of symptoms over time. 

Most carrier females (about 80-90%) have no problems with their skeletal muscles. Some have mild muscle weakness, fatigue (a tired feeling), pain, or cramping in their muscles. Rarely, a carrier has symptoms that are as severe as those of a male with muscular dystrophy. These issues should be addressed by specialists in these areas (ie, neuromuscular specialists (neurology or physical medicine and rehabilitation (PM&R), physical therapy, etc.) and followed regularly. They may suggest stretches, exercises, and/or medication for pain that may be helpful. 

Carrier females have an increased chance of changes to heart function. It is not yet known how common heart changes are, but some studies have estimated that 10-50% of carriers have heart changes. Because a small percentage of carriers may have serious heart concerns, however, it is important for all women who are carriers and women who are at risk to be carriers (for example, women with a son or brother with Duchenne) to have regular heart evaluations, beginning in their late teens/early adult years and, if normal, repeated every 3-5 years.

How is dystrophinopathy passed through female carriers?

Each time a carrier has a child, there is a 50% chance (or 1 out of 2 chance) that they will inherit the same DMD gene variant. For male children (sons), inheriting this DMD gene variant is usually expected to result in dystrophinopathy. For female children (daughters), inheriting this DMD gene variant means that they are carriers and also have some chance to develop symptoms of dystrophinopathy. Learn more about Inheritance here.

How do I know if I’m a carrier?

Sometimes, a personal or family history can suggest if someone is likely to be a carrier or not, but the only way to confirm carrier status is with genetic testing. Genetic testing usually uses DNA from a blood draw or cheek swab to analyze the DMD gene for variants. Genetic testing is not perfect, but if the laboratory completing your testing has a copy of the genetic test results from a relative with a DMD variant, it is very accurate. Learn more about carrier testing.

How can being a carrier affect a woman’s health?

Learning that you are a carrier can be overwhelming, especially if it coincides with your child being diagnosed with dystrophinopathy. Talk to your doctor to develop a timeline for taking these next steps. 

1. Find your sources of support: It is important to take time to process a diagnosis and find your support resources. Support looks different to every person. This could mean sharing with friends or family, reaching out to our PPMD for You team to learn more about a new diagnosis, joining a Connect group to meet other families, or keeping a journal to process.
2. Establish your medical team: While some carriers will never experience any physical symptoms, others will go on to experience a variety of symptoms with variable severity. While you may need none, some, or all of the specialists below, an experienced medical team can help offer guidance on appropriate screenings, symptom management, or offer guidance and answers to your questions.
   • Heart Care: It is strongly recommended that carriers see a cardiologist for regular heart screening, even if they don’t think they have heart symptoms. A referral to a cardiologist is generally made at the time of diagnosis as a carrier, and regular screenings will often be scheduled, even if symptoms or heart changes are not found at the first appointment.
   • Muscle Care: Symptoms vary and may include weakness, balance issues, muscle pain or fatigue, difficulty with exercise, as just some of the potential symptoms.  A neuromuscular specialist can help with understanding the cause of your symptoms and explore resources to feel better.
   • Mental Health Care: Carriers can have psychological symptoms, either related to the DMD variant itself or the impact of learning about a variant. A therapist or psychologist can be a useful ally in navigating psychological symptoms.
   • Reproductive Care: If you are thinking of having children in the future, you have many options to grow your family. Speaking to a prenatal genetic counselor can help you decide which option is best for you.
     Click here to learn more about who your medical team might include. Some states have clinics dedicated to carriers, which you can learn more about here.
3. Talk to biological relatives about genetic testing: Once a genetic variant is found in someone, relatives of that person – including extended relatives – can complete genetic testing themselves to know if they are at risk for dystrophinopathy symptoms. There could be several more carriers or even young relatives with dystrophinopathy found in an extended family. Relatives can use the Decode Duchenne program to receive genetic testing for free.

What if my carrier testing came back negative?

Most people who receive negative genetic test results are not at risk of dystrophinopathy symptoms and do not have an increased chance of passing on a DMD variant. Talk to your doctor or genetic counselor to understand if there were any limitations to your genetic testing that could reduce its accuracy.

However, there are people who have had more than one child with dystrophinopathy, even after negative carrier testing. This is due to “germline mosaicism” (also called “gonadal mosaicism”), which means that someone’s egg or sperm cells have different DNA from the rest of their body. If the mother of a child with dystrophinopathy has germline mosaicism, she does not have the variant in her saliva or blood, so it is not detected by genetic testing. She generally is not expected to develop symptoms. But because the variant is in some of her egg cells, there is an increased chance to have another child with the variant. Learn more about germline mosaic carriers.

How can I find more information and connect with other carriers?

You can explore the For Carriers web pages to find more information about carrier care, reproductive options, and relevant publications. Establish care with a medical team familiar with carrier health to learn more about what being a carrier means for you as an individual. You may also find it useful to connect with the PPMD For You team members to ask targeted questions about your genetics or next steps in your healthcare plan, or to meet with other carriers through our Connect groups, Carrier Meetings, or other PPMD events.