Manifesting carriers of Duchenne and Becker muscular dystrophy

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are conditions caused by a genetic change on the X chromosome. These conditions mostly affect males, while females are usually carriers. Most female carriers don’t experience any symptoms themselves. However, there are some cases where females show symptoms of DMD or BMD, they are known as a manifesting carrier.

For information on BMD, see our Becker muscular dystrophy page.

For information on DMD, see our Duchenne muscular dystrophy page.

The symptoms experienced by manifesting carriers of DMD and BMD can vary widely. In some instances, the symptoms are mild, while in some others, they can progress to the symptoms seen in people with Duchenne muscular dystrophy.

Muscle weakness

Typically, manifesting carriers can experience mild muscle weakness that begins in early to late adulthood. Like BMD and DMD, weakness typically starts around the muscles in the hip and legs. The person may struggle to climb stairs, run, or walk long distances. As the condition progresses, muscle weakness then affects the shoulders and arms. It could become difficult to lift heavy objects above waist level or raise the arms above the shoulders. Muscle weakness is expected to slowly worsen over time. In some manifesting carriers, the weakness can be severe. But this is rare.

Some people will have enlarged calves, which is a typical feature in X-linked muscular dystrophies. Some may find that one side of their body is weaker than the other. This is called asymmetry. Other possible symptoms include fatigue, muscle aches, and pains.

Cardiac

Manifesting carriers are at risk of having cardiomyopathy – heart muscle weakness that affects the heart’s ability to pump blood around the body. A manifesting carrier could have cardiomyopathy even if they don’t have muscle weakness. Symptoms of cardiomyopathy could be mild, like feeling dizzy or out of breath. Cardiomyopathy should be monitored regularly and treated with medication.

Respiratory

In some cases, manifesting carriers may have mild respiratory problems such as reduced lung function or a weak cough, as the muscles used for breathing can weaken. This should be regularly monitored in a clinic.

Neurodevelopment

Learning difficulties and behavioural conditions can be more common in people with BMD and DMD. This is because dystrophin, the same protein missing in the muscles, is also found in the brain. Some manifesting carriers might also have these conditions.

Genetic changes

Duchenne and Becker muscular dystrophies are caused by changes in the dystrophin gene, which is located on the X chromosome. The dystrophin gene contains instructions to make the dystrophin protein. This protein maintains the structure of the muscles. In manifesting carriers, the production of dystrophin is disrupted and not enough of it is produced. This can lead to weakness in the skeletal muscles, breathing muscles, and heart muscle.

Inheritance

DMD and BMD are inherited in an X-linked recessive pattern. This means that the genetic change causing the condition is located on the X chromosome. As the male sex have only one X chromosome and the female sex have two, males are typically more affected by DMD and BMD. In most cases, the second X chromosome that females have is able to ‘protect’ them from developing the condition and symptoms. This is because the normal gene on the other X chromosome can make the dystrophin. These individuals are carriers.

For more information, see our inheritance and genetics page.

In manifesting carriers, a process called skewed X-inactivation happens. This is where the normal X chromosome is inactivated instead of the X chromosome with the genetic change. This means that the X chromosome that has the change can’t instruct the body to make enough dystrophin. When this happens, it causes symptoms of the condition in females too.

A combination of medical and family history, physical examination, and genetic testing undertaken by a neurologist can all be used to diagnose manifesting carriers. A neurologist is a doctor who specialises in conditions that affect the muscles and nervous system. A GP can make a referral to a neurologist. Getting a genetic diagnosis is important for effective management and allows the person to seek genetic counselling.

If you have a family history of DMD or BMD

If male relatives have been diagnosed with DMD or BMD, genetic testing is recommended to identify female carriers. This test analyses a blood sample to find changes in the dystrophin gene. The relative’s neurologist can arrange this, or a GP can make a referral.

It’s not possible to know if someone is a manifesting carrier until symptoms like mild muscle weakness or heart problems begin. A physical examination can help identify muscle weakening and wasting. There is no evidence to suggest that being a manifesting carrier runs in families. If one member of the family is a manifesting carrier, it doesn’t mean that other female family members are more likely to also show symptoms.

If you have no family history of DMD or BMD

Diagnosing manifesting carriers without a family history of DMD or BMD is more challenging because the symptoms could be similar to other conditions. Blood tests might show high levels of a protein called creatine kinase (CK) and liver enzymes (ALT/AST) due to muscle damage. However, CK and ALT/AST levels could be normal in some manifesting carriers.

Sometimes, a muscle biopsy is necessary to see if the muscle is producing some dystrophin, but in reduced amounts. It will also help further analyse the dystrophin gene in the muscle. Genetic testing, using a blood sample, can then confirm if a person is a carrier by identifying changes in the dystrophin gene. It’s not possible to know if someone is a manifesting carrier until symptoms like mild muscle weakness or heart problems begin.

A multi-disciplinary approach is important in not only managing the condition and symptoms but in improving wellbeing too. The type and severity of symptoms experienced by manifesting carriers varies significantly, and so will the management and care required.

Access to a healthcare team

Manifesting carriers should have access to a multi-disciplinary healthcare team. Usually, the lead professional will be a neurologist. If you do not have contact with a neurologist or specialist doctor, ask your GP about getting access to one. Some adults with minor symptoms may not need regular follow up appointments – this should be decided with the neurologist.

Cardiac

Cardiomyopathy could be the only symptom some manifesting carriers experience. So, it’s important to have regular heart monitoring appointments with a cardiologist. An electrocardiogram (ECG), echocardiogram (ECHO), and Holter monitoring may be required. All carriers or women at high risk of being carriers, whether manifesting or not, should have a heart check at the time of diagnosis. They may then need heart checks every three to five years.

Early treatment of heart problems with drugs called ACE inhibitors and/or beta-blockers can protect the heart muscle and reduce the risk of developing severe cardiomyopathy and heart failure. Any symptoms, such as shortness of breath, palpitations, dizziness, and chest pain must be reported to healthcare professionals.

Exercise and physiotherapy

Staying active and maintaining strength is important. Having a good sleep routine, diet, exercising regularly and maintaining a healthy weight will help with symptoms of fatigue. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can put together a suitable exercise plan. Regular stretching can help keep muscles flexible and prevent joint tightness. Strengthening exercises can help to prevent muscle weakening, and aerobic exercise such as walking, swimming, and cycling can help keep the heart and lungs as healthy as possible. After exercise, allow time to fully recover the next day. Some muscle soreness is okay, but this should not be severe pain and should improve over time. To find out more about advice for adults, see exercising with a muscle wasting condition.

Managing pain

Some manifesting carriers experience severe aches and pains in their muscles even when they aren’t active. Discussing appropriate pain relief with a neurologist or GP is important. Taking part in exercise is possible but should be talked through with a physiotherapist.

Pregnancy

Planning to have a baby is important for anyone. For someone diagnosed as a carrier or manifesting carrier of BMD or DMD, it’s important to have a discussion with the neuromuscular team, cardiologist, specialist nurse, or genetics team. They can give advice about what to consider before trying to conceive. And they can help you understand the risks, talk about choices in family planning, and whether to consider options to help prevent passing on the genetic changes of BMD or DMD.

If already pregnant, a referral by a GP or neuromuscular team should be made as soon as possible. Specialist cardiac care should be considered in all carriers before pregnancy or as soon as pregnancy is confirmed. This is especially important in manifesting carriers. Those with cardiomyopathy should be treated as high risk and monitored by a high-risk obstetrician and a cardiologist. Throughout pregnancy, regular check-ups are important for monitoring the health of the parent and the baby’s growth as pregnancy can be difficult on the body.

Anaesthesia stops a person feeling pain during a procedure or surgery. Manifesting carriers are at a higher risk of complications during general anaesthesia. This can be because of heart and breathing issues or adverse reactions to some general anaesthetics. It’s crucial that the anaesthetist and surgical team are aware of the diagnosis and any cardiac and respiratory complications. A pre-operative assessment and extended post-operative monitoring is necessary. Specialist neuromuscular clinics can be contacted for advice if needed.

Avoid use of suxamethonium, inhaled anaesthetics, and neuromuscular blocking drugs. This is due to high risk of acute rhabdomyolysis, which is life-threatening. Rhabdomyolysis is the rapid breakdown of muscles causing muscle pain and dark red or brown coloured urine. If this happens, the person must be urgently admitted to hospital for assessment, administration of IV fluids, and monitoring.