Duchenne muscular dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy, a group of genetic disorders that cause progressive muscle weakness and wasting. The condition usually appears in early childhood and almost always affects boys.

Although there is no cure for DMD, there are treatments available to slow disease progression and improve quality of life. Advances in treatment and care have steadily improved the long-term outlook for people with DMD.

What is DMD?

DMD is a type of muscular dystrophy caused by mutations in the DMD gene. Symptoms usually start in early childhood, around ages 2 or 3, and worsen over time.

At first, DMD causes weakness in the muscles near the center of the body — the shoulders, upper arms, hips, and thighs. As the disease progresses, it affects other muscles, including those that control the heart and lungs. Most people with DMD lose their ability to walk by early adolescence, and nearly all have significant heart problems by adulthood.

DMD is the most common type of muscular dystrophy, but it is overall a rare disease. It occurs in about one in every 3,500 live male births worldwide.

What causes DMD?

DMD mutations cause DMD by disrupting production of dystrophin, a protein that acts like a shock absorber to help protect muscle cells from damage during movement. Without enough working dystrophin, muscles are vulnerable to damage and deterioration.

Researchers have identified more than 2,000 mutations in the DMD gene that can cause a form of muscular dystrophy. Those that cause DMD usually result in very little or no functional dystrophin. Other DMD mutations that allow some functional dystrophin to be made lead to Becker muscular dystrophy (BMD), which tends to be milder and start later than DMD.

How DMD is inherited

DMD is most often inherited, meaning a child receives the disease-causing mutation from a biological parent. DMD inheritance generally follows an X-linked recessive pattern, which is why the disorder primarily affects boys and men. The DMD gene is located on the X chromosome, one of the two types of sex chromosomes in humans. Most people assigned male at birth have one X chromosome, while most people assigned female at birth have two.

• Males: those who inherit a faulty DMD gene on their only X chromosome produce little to no working dystrophin and will develop DMD
• Females: those who inherit a DMD-causing mutation on one X chromosome generally have a healthy copy of the gene on their other X chromosome, enabling enough dystrophin production to avoid symptoms

Females who inherit one mutated copy of DMD are genetic carriers. They can pass the mutation to their biological children even if they have no symptoms. A minority of carriers develop symptoms, but they are typically less severe and may appear later than those that occur in males.

The chances a child will develop DMD depend on which parent carries the disease-causing mutation:

• Man with DMD and a non-carrier woman: children with one X chromosome will not inherit DMD, while 100% of children with two X chromosomes will be carriers
• Man without DMD and a female carrier: there is a 50% chance any children with one X chromosome will inherit DMD, and a 50% chance any child with two X chromosomes will be a carrier

In about 30% of DMD cases, the disease-causing mutation arises randomly without being inherited. These are called de novo cases.

DMD symptoms and progression

As with other types of muscular dystrophy, the main symptoms of DMD are progressive muscle weakness and wasting. In DMD, this typically starts in the muscles near the trunk and spreads to other muscles as the disease progresses.

While DMD symptoms usually begin in toddlerhood, some less obvious signs may appear earlier, including:

• Slightly decreased muscle tone in infancy
• Difficulty holding the head up or controlling its movement
• Delayed developmental milestones, such as walking and speaking
• Slow growth and short stature

Clearer DMD symptoms generally begin around the age of 2 or 3, although this may vary. Depending on the child, early symptoms may include:

• Unusual ways of walking, such as walking on toes or with a waddling gait
• Difficulty running or climbing stairs
• Frequent falls and clumsiness, which may result in injuries
• Enlarged calves due to a buildup of scar tissue and fat in calf muscles
• Gower’s maneuver — using the hands to push against the legs when standing up from the floor

About 20% to 30% of people with DMD have intellectual disability, which can cause behavioral symptoms or difficulties with learning. Others might have milder learning impairment.

As DMD progresses, movement problems generally get worse and eventually lead to an inability to walk. As additional muscle groups are affected, other symptoms and complications often develop, including:

• Spinal curvature: excessive inward (lordosis) or sideways (scoliosis) curving of the spine
• Contractures: joint stiffness that often affects the ankles, knees, hips, or elbows
• Throat weakness: weakness in throat muscles can cause difficulties with swallowing or voice changes
• Heart problems: damage to the heart muscle can cause abnormal heart rhythms and other symptoms
• Respiratory problems: weakness in the muscles that support breathing can cause breathing difficulties

The timeline of DMD progression varies from person to person, and not everyone will experience every symptom. However, most people with DMD will require a wheelchair by the age of 12 and will have significant heart problems by their early twenties.

Diagnosis

Establishing a DMD diagnosis requires similar types of testing as a general diagnosis of muscular dystrophy.

Early signs and symptoms of DMD can lead doctors to suspect the disease and recommend further testing, especially if there is a family history of muscle disorders. Doctors will then typically order tests to confirm the diagnosis and rule out similar conditions.

Symptoms consistent with DMD and elevated creatine kinase levels are usually enough to prompt genetic testing, which is the definitive way to confirm a DMD diagnosis. Muscle biopsies are now rarely used to diagnose DMD but may be considered when genetic testing is inconclusive. Electromyography is also rarely needed for DMD diagnosis.

Female relatives of a person with DMD may undergo genetic testing to see if they are carriers. Genetic counselors can help families understand which relatives should get tested and what the results might mean.

Heart, breathing, and other complications to monitor

Over time, DMD can cause several complications, including problems with the heart, lungs, and other body systems. These can affect life expectancy and quality of life, which is why lifelong monitoring and care are necessary.

Heart problems

By early adulthood — and often sooner — virtually all people with DMD develop heart problems, which are a leading cause of death in DMD. Dystrophin loss causes the heart muscle to weaken. Heart cells die off and are replaced by fat and scar tissue.

The main heart problem in DMD is dilated cardiomyopathy, a condition in which the heart becomes enlarged and its weakened muscle struggles to pump blood throughout the body. This can eventually lead to heart failure. Many people also develop heart rhythm abnormalities.

Detecting heart problems early is important for getting appropriate treatment. Children with DMD should receive regular tests of heart structure and function — including an echocardiogram and electrocardiogram — and be monitored for warning signs such as shortness of breath and chest pain. Some children will start heart medications even when tests are still normal.

Lung problems

Most people with DMD also develop breathing problems because dystrophin loss weakens the muscles used for breathing. While this has historically been another major contributor to early death in DMD, outcomes have been improving with advances in respiratory care.

Breathing problems may first appear during sleep, such as sleep apnea, and may progress to breathing difficulties during the day. Some people develop chronic respiratory failure, in which weakened breathing muscles prevent the body from getting enough oxygen or removing enough carbon dioxide.

Regular lung function tests can help doctors identify early signs of a breathing problem and treat them promptly. These tests generally become more frequent after a child loses the ability to walk, as breathing issues usually worsen at that point. Many people with DMD benefit from noninvasive ventilation, which helps them breathe using a mask over the nose or face.

Bone problems

Weak muscles around the spine can cause it to curve abnormally. Scoliosis often develops in early adolescence, after children with DMD lose their ability to walk. In turn, scoliosis can compress the chest and contribute to breathing problems. Other orthopedic problems are also common, such as joint contractures and pain.

Children with DMD need regular monitoring for bone and joint problems. Braces or shoe inserts may help manage some of these problems, while corrective surgery may be considered in more severe cases.

Treatment and supportive care

There is no cure for DMD, but several treatment options are available. A multidisciplinary DMD treatment plan can help ease symptoms, slow disease progression, extend survival, and improve quality of life. Clinical guidelines recommend a combination of medications and non-drug treatments tailored to an individual’s needs.

Medications

Several medications are available to treat DMD. Some can help preserve muscle strength and function and slow disease progression.

Corticosteroids are a foundation of DMD treatment. These powerful anti-inflammatory medications can help protect muscles from damage, slow declines in muscle strength, and preserve function. They are usually started early in life.

Other disease-modifying medications approved for DMD include:

• Gene therapies: treatments that deliver a shortened version of the DMD gene, allowing the body to produce a smaller, partially functional dystrophin protein
• Exon-skipping therapies: medications that change how RNA from the DMD gene is processed, allowing the body to produce shortened, partially functional dystrophin
• Histone deacetylase inhibitors: medications that target processes involved in inflammation and muscle loss

The choice of medications may depend on several factors, including a person’s age and specific DMD mutation.

Most people with DMD will also receive standard medications to help protect the heart.

Non-drug treatment

Supportive care strategies can help preserve function, ease symptoms, and improve overall quality of life in people with DMD. These may include:

• Physical therapy: exercises and stretching to help maintain mobility and muscle function
• Occupational therapy: supports participation and independence in daily activities
• Speech therapy: addresses problems with speech and swallowing
• Surgery: can correct certain skeletal complications, such as scoliosis
• Breathing support: devices such as ventilators to assist breathing and cough-assist devices to help clear mucus
• Assistive devices: to support mobility and communication
• Nutritional support: helps people with DMD get the nutrients they need and maintain a healthy diet

Long-term outlook of DMD

DMD prognosis has improved greatly with advances in treatment and monitoring, although the disease still affects life expectancy.

Historically, median survival for people with DMD who did not receive ventilatory support was about 19 years. With advances in breathing support and other DMD care, many people with DMD are now living into their 30s, and some into their 40s. Heart and breathing problems remain the leading causes of death in DMD.

Advances in DMD care also mean that many people living with DMD can maintain independence for longer and have an overall better quality of life. 

---

Muscular Dystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.