Duchenne Muscular Dystrophy (DMD)

What is Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is a condition that weakens skeletal and heart muscle that quickly gets worse with time. It’s the most common form of muscular dystrophy.

Most cases of DMD are inherited as an X-linked recessive trait (passed on through the mother, who is a carrier), but approximately 30% of cases are due to new genetic changes (mutations) that happen randomly and aren’t inherited.

Who does Duchenne muscular dystrophy affect?

Duchenne muscular dystrophy mainly affects boys, but girls who are carriers for DMD can sometimes have milder symptoms.

Symptoms of muscle weakness usually appear by the age of 2 years to 4 years, but sometimes, are noted as late as 6 years.

How common is Duchenne muscular dystrophy?

Duchenne muscular dystrophy affects about 1 in 3,600 male live-born infants. It’s the most common type of severe hereditary myopathies (disorders of skeletal muscles).

Is Duchenne muscular dystrophy fatal?

Yes, Duchenne muscular dystrophy is ultimately fatal. Most people with the condition die from lung or heart issues caused by it.

What are the symptoms of Duchenne muscular dystrophy?

Symptoms of Duchenne muscular dystrophy (DMD) most often appear between the ages of 2 and 4 years, though they can begin as early as infancy or be noticed later in childhood.

DMD causes muscle weakness that worsens over time, so common symptoms include:

• Progressive muscle weakness and atrophy (loss of muscle bulk) that begins in your child’s legs and pelvis. It occurs less severely in their arms, neck and other areas of their body.
• Calf muscle hypertrophy (increase in muscle size).
• Difficulty climbing up stairs.
• Difficulty walking that gets worse over time.
• Frequent falls.
• Waddling gait (walk).
• Toe walking.
• Fatigue.

Other common symptoms of DMD include:

• Cardiomyopathy.
• Breathing difficulties and shortness of breath.
• Cognitive impairment and learning differences.
• Delayed speech and language development.
• Developmental delay.
• Scoliosis (spine curvature).
• Short stature (height).

About 2.5% to 20% of girls who are carriers of DMD may have symptoms that are usually milder.

What causes Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is caused by a change (mutation) in the gene that gives instructions for a protein called dystrophin. Dystrophin is a critical part of the dystrophin-glycoprotein complex (DGC), which plays an important role as a structural unit of muscle.

In DMD, both dystrophin and DGC proteins are missing, which ultimately leads to the death (necrosis) of muscle cells. People with DMD have less than 5% of the normal quantity of dystrophin needed for healthy muscles.

As people with DMD age, their muscles can’t replace the dead cells with new ones, and connective and adipose (fat) tissue gradually replaces muscle fibers.

Duchenne muscular dystrophy has X-linked recessive inheritance, but about 30% of cases happen spontaneously without a family history of the condition.

X-linked means the gene responsible for DMD is located on the X chromosome, one of two sex chromosomes. Males have an X and Y chromosome, and females have two X chromosomes.

Genes, like chromosomes, usually come in pairs. Recessive means that when there are two copies of the responsible gene, both copies must have a disease-causing change (pathogenic variant or mutation) for a person to have the condition. Since males only have one X chromosome, if that chromosome has the genetic variant that causes DMD, they’ll have DMD.

How is Duchenne muscular dystrophy diagnosed?

If your child is experiencing symptoms of Duchenne muscular dystrophy (DMD), your child’s healthcare provider will likely perform a physical exam, neurological exam and muscle exam. They’ll ask detailed questions about your child’s symptoms and medical history.

If your child’s provider suspects that your child may have DMD, they’ll likely order the following tests:

• Creatine kinase blood test: Your muscles release creatine kinase when they’re damaged, so elevated levels may indicate DMD. Levels typically peak by age 2 and can be more than 10 to 20 times above the normal range.
• Genetic blood test: A genetic blood test that looks for a complete or near-complete absence of the dystrophin gene can confirm the diagnosis of DMD.
• Muscle biopsy: Your child’s provider may take a small sample of their muscle tissue from a muscle in their thigh or calf. A specialist will then look at the sample under a microscope to look for signs of DMD.
• Electrocardiogram (EKG): As DMD almost always affects your heart, your child’s provider will likely perform an EKG to look for characteristic signs of DMD and to check the health of your child’s heart.

How is Duchenne muscular dystrophy treated?

There’s currently no cure for Duchene muscular dystrophy (DMD), so the main goal of treatment is to manage symptoms and improve quality of life.

Supportive therapies for DMD include:

• Corticosteroids: Corticosteroids, such as prednisolone and deflazacort, are beneficial for delaying muscle strength loss, improving lung function, delaying scoliosis, slowing the progression of cardiomyopathy (heart weakness) and prolonging survival.
• Medication to treat cardiomyopathy: Early treatment with ACE inhibitors and/or beta-blockers may slow the progression of cardiomyopathy and prevent the onset of heart failure.
• Physical therapy: The main goal of physical therapy for DMD is to prevent contractures (permanent tightening of your muscles, tendons and skin). This usually involves certain stretching exercises.
• Surgery to help treat scoliosis and contractures: Surgery to release contractures may be necessary for severe cases. Surgery to correct scoliosis may improve lung and breathing function.
• Exercise: Your child’s healthcare provider will likely recommend gentle exercise to avoid muscle atrophy due to a lack of use. This is usually a combination of swimming pool and recreation-based exercises.

Other supportive therapies for DMD include:

• Mobility aids, such as braces, canes and wheelchairs.
• Tracheostomy and assisted ventilation for respiratory failure.

With improvement in supportive care over the years, the life expectancy of DMD has significantly improved over the past few decades.

There are many new drugs currently undergoing clinical testing that show promise in treating DMD. Some newer treatments that employ “exon skipping” (patching over a missing or mutated part of the dystrophin gene) have recently received FDA (Food and Drug Administration) approval. These treatments are applicable only to a minority of cases that have very specific mutations. Although these treatments increase dystrophin protein amount in muscle, meaningful gain in strength and physical function has not yet been shown.

What is the prognosis of Duchenne muscular dystrophy?

The prognosis is often poor for people with Duchenne muscular dystrophy (DMD). It leads to progressively worsening disability, and most children with DMD need to use a wheelchair by the age of 12. DMD ultimately results in death at an early age.

What is the life expectancy of Duchenne muscular dystrophy?

People with Duchene muscular dystrophy often die from the condition by the age of 25 years. However, advances in supportive care have resulted in many people living longer.

Death often occurs as a result of respiratory (breathing) or heart complications. Other causes of death include pneumonia, aspiration (breathing in a foreign object, such as food) or airway obstruction.

Can Duchenne muscular dystrophy be prevented?

As Duchenne muscular dystrophy (DMD) is an inherited condition, there’s nothing you can do to prevent it. About a third of cases happen randomly without a family history of the condition.

If you’re concerned about the risk of passing on DMD or other genetic conditions before trying to have a biological child, talk to your healthcare provider about genetic counseling. In some situations, prenatal testing may be able to diagnose DMD in early pregnancy.

How do I take care of someone with Duchenne muscular dystrophy?

If you’re taking care of someone with Duchenne muscular dystrophy (DMD), it’s important to advocate for them to ensure they get the best medical care and access to therapy that can help them have the best quality of life.

You and your family may also want to consider joining a support group to meet others who can relate to your experiences.

When should my child see their healthcare provider about Duchenne muscular dystrophy?

If your child has been diagnosed with Duchenne muscular dystrophy, they’ll need to see their team of healthcare providers regularly to receive treatment and monitor symptoms.