Duchenne Muscular Dystrophy

Overview

Duchenne muscular dystrophy (DMD) is a progressive form of muscular dystrophy that occurs primarily in males, though in rare cases may affect females. DMD causes progressive weakness and loss (atrophy) of skeletal and heart muscles. Early signs of DMD may include delayed ability to sit, stand, or walk and difficulties learning to speak. Muscle weakness is usually noticeable by 3 or 4 years of age and begins in the hips, pelvic area, upper legs, and shoulders. The calves may be enlarged. Children with DMD may have an unusual walk and difficulty running, climbing stairs, and getting up from the floor. DMD may also affect learning and memory, as well as communication and certain social emotional skills. Muscle weakness worsens with age and progresses to the arms, legs and trunk. Most children with DMD use a wheelchair full time by age 13. Heart and respiratory muscle problems begin in the teen years and lead to serious, life threatening complications.

DMD is caused by changes (mutations) in the DMD gene. The DMD gene codes for the protein dystrophin. Dystrophin is mainly made in skeletal and heart muscle cells, but a small amount is also made in nerve cells (neurons) in specific parts of the brain. DMD is inherited in an X-linked recessive pattern; however, it may also occur in people who do not have a family history of DMD. While there is no known cure for DMD, there are treatments that can help control symptoms. Due to the advancement of medical treatment, boys with DMD may now live into young adulthood.

Becker muscular dystrophy (BMD) is also caused by mutations in the DMD gene. People with BMD have less severe symptoms than DMD. In addition, symptoms start later in childhood or in adolescence and progress more slowly.

Symptoms

Symptoms of Duchenne muscular dystrophy (DMD) are usually noticed in boys between 1 to 6 years of age. There is a steady decline in muscle strength between the ages of 6 and 11 years. By age 10, braces may be needed for walking. By age 13, most boys with DMD are using a wheelchair full-time. The signs and symptoms include:

• Taking longer to learn to sit, stand, or walk on own, which is known as delayed motor development. The average age for walking in boys with DMD is 18 months.
• Having a waddling walk and difficulty climbing stairs or running.
• Difficulty getting up from the floor. Children may walk their hands up their legs to stand which is known as the Gower maneuver.
• Enlarged calf muscles due to the calf muscle cells being replaced by fat and connective tissue (pseudohypertrophy). This may also cause calf pain.
• Muscle weakness first affecting the muscles of the hips, pelvic area, thighs and shoulders, and later the skeletal (voluntary) muscles in the arms, legs and trunk.
• Tight or rigid joints (also known as contractures) may develop as muscle loss progresses. If not treated, these will become severe, causing discomfort and restricting mobility and flexibility. Contractures can affect the knees, hips, feet, elbows, wrists and fingers.
• Scoliosis may develop within several years of full-time wheelchair use.
• By the early teens, the respiratory and heart muscles are also affected.
• Breathing problems due to weakness of the diaphragm and the other muscles around the lungs. Skeletal changes, such as scoliosis, may also increase breathing problems. Breathing problems may become life-threatening.
• Progressive enlargement of the heart (cardiomyopathy) that stops the heart from pumping blood efficiently, and becomes life-threatening in many cases.
• Learning and memory issues (cognitive impairment) may occur in some cases, but do not worsen as DMD progresses.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene. The DMDgene provides instructions for making a protein called dystrophin. Dystophin is primarily made in the muscle cells of the heart and skeletal muscle. The main job of dystrophin in muscle cells is to help stabilize and protect muscle fibers.

Small amounts of dystrophin are also made in nerve cells (neurons) in specific parts of the brain, including the hippocampus. The hippocampus is the part of the brain involved in learning and memory, as well as emotions. Scientists do not yet understand the job of dystrophin in neurons.

DMD is caused by genetic changes in the DMD gene that stop any functional dystrophin from being made. When dystrophin is missing, the muscle cells become damaged more easily. In response to the damage, inflammation occurs, which only worsens the process. Over time, the muscle cells without dystrophin weaken and die, leading to the muscle weakness and heart problems seen in DMD. The non-progressive memory and learning problems, as well as social behavioral problems, in some boys with DMD are most likely linked to loss of dystrophin in the neurons of the hippocampus and other parts of the brain where dystrophin is normally produced in small amounts, but at this point it is not known why this occurs and why only some people with DMD have these problems.

Different genetic changes in the DMD gene can cause a spectrum of disorders known as dystrophinopathies. The dystrophinopathies can range from very mild symptoms to the more severe symptoms seen in people with DMD. Other dystrophinopathies include Becker muscular dystrophy (BMD) and DMD-associated dilated cardiomyopathy (DCM).

Inheritance

Genetic changes causing Duchenne muscular dystrophy (DMD) can be passed down in families. The DMD gene is located on the X chromosome, one of the two types of sex chromosomes. Males have an X and a Y chromosome; whereas females have two X chromosomes. Since males only have one X chromosome, they also only have one copy of the DMD gene. If this copy has a genetic change that causes DMD, the male will have DMD. Males get their X chromosome from their mother and the Y chromosome from their father.

Since females have two X chromosomes, they have two copies of the DMD gene. Having two changed copies of the DMD gene that can cause DMD is unlikely, but would cause DMD in females. A female with only one changed copy of the DMD gene is called a “carrier”. She can pass on the changed gene, but usually does not have symptoms of DMD. Carriers of changes in the DMD gene that can cause DMD are at an increased risk of developing heart problems, including cardiomyopathy. In addition, due to a process called X-inactivation, in rare cases, female carriers may have mild, moderate, or severe DMD.^[

If a man with DMD has children, all of his daughters will be carriers. Since boys inherit the Y chromosome from their father, sons will not inherit DMD from their fathers, even if the father has DMD.

Women who are carriers of a change in the DMD gene that can cause DMD have a 50% chance of passing it on to each child, whether the child is a boy or a girl. In other words, each daughter will have a 50% risk of being a carrier. Each son will have a 50% risk of having DMD.^[

In some cases, a child is the first person in his family to be diagnosed with DMD. This can happen if the change in the DMD gene happened by mistake during the making of the egg or sperm. When this happens it is called a new or de novo mutation. In this case, the risk that the mother would have another child with DMD is low. However, sometimes, the boy’s mother is a carrier of DMD, but is the first person in her family with the change in the DMDgene. This means the change in the DMD gene happened by mistake during the making of the egg or the sperm that came together to form the fertilized egg that developed into her. In this case, the mother is a carrier and would have a 50% risk that each son will have DMD and also a 50% risk that each daughter will be a carrier. To complicate the inheritance even more, a woman may not have the change in the DMD gene in all of her cells. She may only have the change in the gene in some of the cells of her body, including her eggs, or even just in some of her eggs. This can happen if the mistake happens after the egg is fertilized, but sometime early in development of the fetus. In these cases the risk of passing the changed gene to her children depends on how many of her eggs are affected.

Since the inheritance of DMD can be complicated, a family with a newly diagnosed child with DMD should speak with a genetic counselor or other genetic specialist to understand if there is a risk of having more children with DMD and to understand the available genetic testing options.

Diagnosis

A child’s doctor may suspect Duchenne muscular dystrophy (DMD) in young boys who have the signs and symptoms of DMD, including progressive muscle weakness. Family history is also important. Blood tests can be used to check for increased levels of certain special proteins called muscle enzymes in the blood which can leak from damaged muscles. Most commonly, the blood level of the enzyme creatine phosphokinase (CPK or CK) is checked, but a doctor may also check the blood levels of transaminases such as aspartate transaminase and alanine transaminase. Finding a change in the DMD genethat can cause DMD through genetic testing confirms the diagnosis of DMD. Testing for DMD may include:^[2][5]

• Blood test which measures the levels of serum creatine phosphokinase(CK or CPK). Very high CK levels indicate muscle damage is causing the muscle weakness, rather than nerve damage.
• Molecular genetic testing (usually blood cells are used) to see whether there is a change or mutation in the DMD gene that can cause DMD or one of the related dystrophinopathies.
• Electromyography can be used to distinguish conditions that only impact the muscles (myotonic) from those that involve that brain and muscles (neurogenic).
• Muscle biopsy is rarely used to diagnose DMD due to the decreased cost and higher accuracy of genetic testing.

Treatment

Although there’s no cure for any form of muscular dystrophy, treatment for some forms of the disease can help extend the time a person with the disease can remain mobile and help with heart and lung muscle strength. There are many clinical trials of new therapies ongoing.

People with muscular dystrophy should be monitored throughout their lives. Their care team should include a neurologist with expertise in neuromuscular diseases, a physical medicine and rehabilitation specialist, and physical and occupational therapists. Some people might also need a lung specialist (pulmonologist), a heart specialist (cardiologist, a sleep specialist, a specialist in the endocrine system (endocrinologist), an orthopedic surgeon and other specialists.

Treatment options include medications, physical and occupational therapy, and surgical and other procedures. Ongoing assessments of walking, swallowing, breathing and hand function enable the treatment team to adjust treatments as the disease progresses.

Medications

• Corticosteroids, such as prednisone and deflazacort (Emflaza), which can help muscle strength and delay the progression of certain types of muscular dystrophy. But prolonged use of these types of drugs can cause weight gain and weakened bones, increasing fracture risk.
• Newer drugs include eteplirsen (Exondys 51), the first medication to be approved by the Food and Drug Administration (FDA) specifically to treat some people with Duchenne muscular dystrophy. It was conditionally approved in 2016. In 2019, the FDA approved golodirsen (Vyondys 53) for treatment of some people with Duchenne dystrophy who have a certain genetic mutation.
• Heart medications, such as angiotensin-converting enzyme (ACE) inhibitors or beta blockers, if muscular dystrophy damages the heart.

Therapy

Several types of therapy and assistive devices can improve the quality and sometimes the length of life in people who have muscular dystrophy. Examples include:

• Range-of-motion and stretching exercises. Muscular dystrophy can restrict the flexibility and mobility of joints. Limbs often draw inward and become fixed in that position. Range-of-motion exercises can help to keep joints as flexible as possible.
• Exercise. Low-impact aerobic exercise, such as walking and swimming, can help maintain strength, mobility and general health. Some types of strengthening exercises also might be helpful. But it’s important to talk to your doctor first because some types of exercise might be harmful.
• Braces. Braces can help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Braces can also aid mobility and function by providing support for weakened muscles.
• Mobility aids. Canes, walkers and wheelchairs can help maintain mobility and independence.
• Breathing assistance. As respiratory muscles weaken, a sleep apnea device might help improve oxygen delivery during the night. Some people with severe muscular dystrophy need to use a machine that forces air in and out of their lungs (ventilator).

Surgery

Surgery might be needed to correct contractures or a spinal curvature that could eventually make breathing more difficult. Heart function may be improved with a pacemaker or other cardiac device.

Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can’t travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

• To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

• Genetics Home Reference (GHR) contains information on Duchenne muscular dystrophy. This website is maintained by the National Library of Medicine.
• MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
• The National Human Genome Research Institute’s (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
• The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

• GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
• Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
• The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
• Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
• Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
• PubMed is a searchable database of medical literature and lists journal articles that discuss Duchenne muscular dystrophy. Click on the link to view a sample search on this topic.

Resources for Kids

• BrainPOP presents the topic of Duchenne muscular dystrophy in a short, animated movie that is available on CheckOrphan’s Web site.  BrainPOP produced this video in partnership with Parent Project Muscular Dystrophy, this four minute video strives to provide kids of all ages with a clear understanding of Duchenne.

Clinical Trials

https://www.cureduchenne.org/cure/clinical-trials/

To learn more about Duchenne Disease and other hematologic disorders, visit https://checkrare.com/diseases/musculoskeletal-diseases/ 

For more information about Duchenne Disease, visit the National Center for Advancing Translational Sciences’ Genetic and Rare
Diseases Information Center a https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy

Resources