Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is a severe genetic disorder that progressively weakens muscles throughout the body, primarily affecting boys and leading to difficulties with movement, breathing, and heart function.
Table of contents
- What is Duchenne muscular dystrophy?
- Genetic causes and inheritance
- Symptoms and progression
- How is DMD diagnosed?
- Life expectancy and prognosis
- Available treatments
- Living with Duchenne muscular dystrophy
What is Duchenne muscular dystrophy?
Duchenne muscular dystrophy, commonly known as DMD, is a genetic disorder characterized by the progressive loss of muscle function throughout the body[3]. It is one of the most severe forms of inherited muscular dystrophies and the most common hereditary neuromuscular disease[4]. This condition affects approximately 1 in every 3,500 to 5,000 male births[1][2].
The disease is caused by mutations in the DMD gene, which is responsible for producing a protein called dystrophin[1]. When functional, dystrophin helps keep muscle cells intact and protects them when they move[2]. Without dystrophin, muscles cannot function or repair themselves properly, making them vulnerable to injury and leading to progressive muscle degeneration and weakness[3].
DMD is a multi-systemic condition, meaning it affects many parts of the body. The disease results in deterioration of the skeletal muscles used for movement, as well as the heart and lung muscles[3]. As time goes on, the loss of muscle tissue and function becomes so severe that affected individuals are unable to carry out activities of daily living and must use wheelchairs[4].
DMD belongs to a group of four conditions known as dystrophinopathies. The other three diseases in this group are Becker muscular dystrophy (a milder condition than DMD), an intermediate clinical presentation between DMD and Becker, and DMD-associated dilated cardiomyopathy (heart disease) with little or no clinical skeletal muscle disease[1].
Genetic causes and inheritance
Duchenne muscular dystrophy is caused by a mutation in the dystrophin gene, which is located on chromosome Xp21[4]. This mutation results in limited production of the dystrophin protein, which in turn causes loss of muscle fiber membrane integrity. The muscles undergo repeated cycles of damage and attempted regeneration, but fibrous connective tissue and fat progressively replace muscle, leading to the clinical features of the disease[4].
The disease is inherited as an X-linked recessive trait, meaning the gene that causes it is on the X chromosome[2]. Boys have one X and one Y chromosome (X comes from their mother, Y comes from their father), while girls have two X chromosomes (one from each parent). Because boys only have one X chromosome, if that X chromosome has the gene change that causes DMD, they will have the disease[2]. They have no backup copy on another X chromosome to make up for it.
Girls, on the other hand, have a backup copy on their other X chromosome and typically won’t be affected. Girls either don’t have symptoms or they’re very mild[2]. Girls may become carriers, meaning they inherit the gene change but don’t have symptoms themselves. They may pass the gene on to their future children[2].
However, approximately 30% of cases are due to new mutations, meaning the gene change happened randomly and wasn’t passed down from the parents[4][2]. There is no way to prevent Duchenne muscular dystrophy[2].
About 2.5% to 20% of female carriers may be affected and show symptoms. This can happen in cases associated with Turner syndrome, certain chromosomal translocations, or when the normal X chromosome becomes inactivated and the X chromosome with the mutation is expressed[4].
Symptoms and progression
Muscle weakness is the principal symptom of DMD[1]. Symptoms typically appear in early childhood, usually between ages 2 and 4, though they can start as early as infancy[2][1]. During the first few years of life, infants may struggle to sit or stand up independently and may start to walk at a later age than their peers[6].
The first thing parents usually notice is that their child isn’t achieving expected motor (muscle movement) milestones. They might also notice that their child falls over often, is clumsy, and walks on their toes[8]. Children with Duchenne often have trouble keeping up with their peers and have progressive muscle weakness of the legs and pelvic muscles[6].
The weakness begins by affecting the proximal muscles (those close to the torso) and later affects the distal limb muscles (those close to the extremities)[1]. In the early stages, DMD affects the shoulder and upper arm muscles and the muscles of the hips and thighs. These weaknesses lead to difficulty in rising from the floor, climbing stairs, maintaining balance, and raising the arms[1].
As the disease progresses through different stages, symptoms change and worsen:
Ages 3-5 (Diagnosis stage): Children struggle with sitting, standing, and walking. Their calves begin to enlarge, causing them to waddle when walking and making it difficult to climb stairs[6]. You might notice these signs: difficulty climbing stairs, running or jumping, frequent falls, increase in calf muscle size, toe walking, using their arms to push themselves up from the ground, and waddling[2].
Ages 6-9 (Muscle deterioration): As the muscles begin to waste, children struggle with stairs and erratically collapse. They are unable to keep up with their peers and can have associated learning difficulties[6].
Ages 9-13 (Loss of walking ability): As people living with Duchenne approach their teens, they are no longer able to walk (known as ‘non-ambulant’) and become wheelchair bound[6]. Many people with this condition use a wheelchair by age 12[17].
Ages 13+ (Heart and lung problems): As the disease progresses, it causes severe muscle deterioration, reduced bone density, and reduced cardiac and lung function. Muscle weakness and skeletal deformities often contribute to breathing disorders and scoliosis (curvature of the spine), and consequently, spinal surgery is common[6]. Cardiomyopathy (an enlarged heart) occurs in almost all cases, from age 13 onwards, or sometimes earlier[6].
Ages 19+ (Ventilator dependent): By the time individuals with Duchenne approach their twenties, they often become dependent on a ventilator or respirator[6].
How is DMD diagnosed?
If your child shows signs of DMD, their doctor will do a physical, neurological, and muscle examination. They’ll also ask about your child’s symptoms and medical history[2].
Diagnosis is usually made by looking at raised levels of an enzyme called creatine kinase in the blood[6][8]. Blood tests look for elevated levels of this enzyme, which can give a guide but not a certain diagnosis[8].
A genetic test for the DMD gene is the best way to diagnose DMD[8]. The genetic tests confirm the diagnosis by identifying mutations in the dystrophin gene. A muscle biopsy can also be done to look for abnormal levels of dystrophin, to confirm a diagnosis[6]. During a muscle biopsy, a small sample of muscle tissue is removed and examined in a laboratory.
Your child’s healthcare provider may refer you to a pediatric neurologist if they suspect DMD, and may order these tests to confirm a diagnosis[2]. Early and accurate diagnosis is important so that appropriate care and treatment can begin as soon as possible.
Life expectancy and prognosis
When Action Duchenne was founded in 2001, the average life expectancy for a young person living in the UK with Duchenne was late teens. It is now late 20s, with more people than ever living into their 30s and 40s[20]. Very few people with Duchenne live beyond the age of 30[6].
Affected patients usually die in their twenties due to respiratory muscle weakness or cardiomyopathy[4]. The most common causes of death are breathing complications and heart failure, as the muscles of these essential organs deteriorate without repair[6].
While there’s no cure, and the disease will shorten life expectancy, treatments are available to slow its progression and help manage symptoms[2]. Duchenne is 100% fatal and there is currently no cure[6], but with proper multidisciplinary care and available treatments, quality of life can be improved and life can be extended.
Available treatments
There is no known treatment modality that halts the progression of the disease; available treatment options are palliative[4]. Current therapy is centered on treatment with corticosteroids and physiotherapy to prevent orthopedic complications[4].
Multidisciplinary care, including neuromuscular, cardiac, respiratory, endocrine, nutritional, psychosocial, and orthopedic management, is recommended for people with DMD in order to manage the varied symptoms experienced by each person[9]. The use of available treatments can help to maintain comfort and function and prolong life[9].
Corticosteroids: Corticosteroids, such as prednisone, deflazacort, and vamorolone, are commonly prescribed to people with DMD to slow the progression of muscle weakness and delay the loss of walking ability[9]. These medications improve strength and prolong the ability to walk[6]. However, long-term steroid use has a range of debilitating side effects, including weight gain, behavioral changes, growth suppression, bone loss, and cataracts[9][6].
Gene therapy and exon skipping drugs: In the last decade, a number of medications have been approved by the US Food and Drug Administration (FDA) to treat DMD[9]. There are currently 8 FDA-approved therapies specific to Duchenne muscular dystrophy. These treatments work in different ways—some aim to slow disease progression, while others help improve muscle function or target specific genetic changes[13].
Supportive care: Treatment also involves managing symptoms and preventing complications. This includes respiratory care (breathing exercises, monitoring respiratory health, and managing equipment such as ventilators or BiPAP machines), cardiac care (monitoring heart function and treating cardiomyopathy), orthopedic care (physical therapy to prevent contractures, treating scoliosis), and nutritional support[9].
Guidelines for the multidisciplinary care for Duchenne muscular dystrophy that address obtaining a genetic diagnosis and managing the various aspects of the disease have been established[5].
Living with Duchenne muscular dystrophy
A DMD diagnosis is devastating, but it doesn’t have to defeat you or your child. People live productive, creative, and fulfilling lives with DMD. More and more young adults with DMD are attending university, pursuing rewarding careers, and even having families of their own[15].
The symptoms of DMD are different for each child, and the rate at which symptoms worsen varies[15]. As DMD is a progressive disease, meaning the symptoms become more apparent over time, it is important to get your child the right treatments and management as soon as possible. This gives your child the best chance of maintaining their independence and quality of life for as long as possible[15].
Building a strong support network is essential. Family, friends, doctors, nurses, therapists, and online communities can all serve as great pillars of support and comfort to fall back on in difficult times[15]. Connecting with other people who are going through DMD can be particularly helpful.
As your child with DMD reaches adulthood, planning ahead can help support the success of future education, employment, and housing efforts[17]. At age 18, individuals can make their own healthcare choices in most states, which means much of the care shifts from family-focused (decisions made by caregivers) to patient-focused[17].
It is important that adults at this stage receive the care and services they need to stay as healthy, independent, and active as they want to be. It is also important to be engaged in a job or career, maintain an active social life, and stay engaged with the community[18].
To help your child make the most of their future, start by finding out what adaptations can be made to enable them to participate in school as fully as possible. They deserve the same access to learning as any other child[15].
