What is muscular dystrophy?

• There are many different types of muscular dystrophy – a group of inherited genetic conditions that gradually cause the muscles to weaken.
• Each type of muscular dystrophy has different symptoms and not all cause disability.
• Two common types are Duchenne and Becker muscular dystrophy, caused by mutations in the same gene on the X chromosome.

What is muscular dystrophy?

• Muscular dystrophy is a term used to describe a group of inherited genetic conditions that cause the muscles to weaken over time, leading to an increasing level of disability.
• Two common types are Duchenne muscular dystrophy and Becker muscular dystrophy, which are both recessive, single gene conditions caused by mutations in the DMD gene, found on the X chromosome.
• People with XY chromosomes only have one copy of the DMD gene, so only need one mutated version to develop the condition.
• People with XX chromosomes have two copies of the DMD gene. Since the condition is recessive, they need two copies of the mutated gene to develop the condition. If they only have one mutated copy of the gene, they can be a carrier of the condition.
• Duchenne muscular dystrophy is the most common form of the condition and causes the most severe symptoms.
• It affects around 1 in 3,500 people with XY chromosomes and the symptoms appear in infancy.
• Becker muscular dystrophy causes less severe symptoms. It affects around 1 in 10,000 people with XY chromosomes and the symptoms appear during a person’s teens.

What is the biology of muscular dystrophy?

• The DMD gene is the largest known gene in the human genome, at 2.2 million bases. It codes for the protein dystrophin, which is found in muscle cells.
• Dystrophin acts like the glue that binds cells together, joining the internal framework of muscle cells with the connective tissue outside of the cells.
• In Duchenne muscular dystrophy, the mutation in the DMD gene means very little dystrophin is produced. This causes muscle cells to become ‘leaky’ and eventually swell and burst. As the cells burst, they are replaced with fat cells and connective tissue reducing the amount of muscle in the body.
• In Becker muscular dystrophy, the mutation in the DMD gene means regular levels of dystrophin are produced but the protein doesn’t function correctly.

What are the symptoms of muscular dystrophy?

Symptoms of Duchenne muscular dystrophy

• The symptoms of Duchenne muscular dystrophy appear at about three years of age.
• Initially, symptoms include difficulty walking and getting off the floor and usually leads to reliance on a wheelchair by 11 years.
• The condition is progressive, meaning it causes gradually worsened muscle weakness.
• As the condition progresses, it begins to impact the heart and the muscles that help with breathing.
• People with Duchenne muscular dystrophy are usually expected to live into their 20s or 30s.

Symptoms of Becker muscular dystrophy

• Symptoms are similar to Duchenne muscular dystrophy, but they generally don’t appear until the patient is in their teens.
• Progression of the disease is much slower than Duchenne muscular dystrophy.
• Since the condition is less severe, it doesn’t affect a person’s life expectancy.

How is muscular dystrophy diagnosed?

• Since muscular dystrophy causes the muscle cells to become ‘leaky’, proteins that are usually only found in the muscle cells can be found in the blood. For example, the enzyme creatine kinase.
• Blood tests can look for proteins like this in the blood as an indicator of the condition in people showing initial symptoms.
• Other tests are needed to confirm the condition and find out more about the spread of any muscle damage.
• These can include:
  • electrical tests on the nerves and muscles
  • chest and heart scans
  • muscle biopsies, where a sample of muscle tissue is removed for testing.
• Genetic testing can also be carried out to look for the characteristic mutation in the DMD gene.

How is muscular dystrophy treated and managed?

• There’s currently no treatment to reverse the muscle wasting, but a range of treatments can help people with muscular dystrophy with their mobility and associated health challenges.
• For example, physiotherapy can help with mobility. Surgery can help to correct posture, such as scoliosis. Medicines, such as steroids, can help to improve muscle strength.
• In 2022, the first patient in the UK received an experimental gene therapy for their Duchenne muscular dystrophy. The gene therapy works by helping the patient make new copies of the dystrophin protein.
• Other research studies and clinical trials are currently being carried out to test other new treatments. For example, a drug called drisapersen is being tested in clinical trials. It acts by forming a ‘bridge’ over the mutation in the DMD gene, enabling the cellular machinery to produce a slightly shorter, but still functional, form of dystrophin.

Screening for muscular dystrophy

• Genetic screening or testing can be used to find out whether a person is carrying a particular genetic mutation that may cause a medical condition, either in the future or in their future children.
• In the case of muscular dystrophy, screening can help to identify whether a person carries a mutated version of the DMD gene and predict whether they will pass the condition onto their children. This is done with a genetic counsellor.
• Genetic testing can also be done for prenatal diagnosis, after 11 weeks of the pregnancy. This is done by either removing tissue from the placenta or taking a sample of amniotic fluid through a needle into the belly. The cells from these samples are then tested for the mutation in the DMD gene.