Overview: What is Duchenne muscular dystrophy?
Duchenne muscular dystrophy (DMD) is the most common of more than 30 chronic, genetic muscle diseases that are summarized under the term “muscular dystrophy”. In all these diseases, more and more functional muscle substance is gradually lost.
Duchenne muscular dystrophy and Becker-Kiener muscular dystrophy
Duchenne muscular dystrophy begins in infancy and progresses slowly over many years. In addition, without proper treatment, it usually leads to death in early adulthood by spreading to the respiratory and heart muscles.
A more favorable form is Becker-Kiener muscular dystrophy. It also begins with weakness of the pelvic and thigh muscles, but is milder and progresses much more slowly, so that some patients are able to maintain their ability to walk into old age.
Duchenne muscular dystrophy – frequency and age
Duchenne muscular dystrophy is rare, but by far the most common form of muscular dystrophy: it occurs in around one in 3,500 newborn boys. The Becker-Kiener muscular dystrophy (BMD) variant is much rarer.
The first signs of DMD appear between the ages of two and six. BMD breaks out after the age of 7, often up to the age of 20, but rarely the disease may not show symptoms until middle to older adulthood.
Duchenne muscular dystrophy: causes and risk factors
DMD is caused by a genetic defect in the so-called dystrophin gene. As a result, the body can no longer produce dystrophin protein. This is a protein that is necessary for a stable cell membrane of the muscle fibers. Due to the dystrophin deficiency in people with Duchenne muscular dystrophy, muscle fibers are therefore increasingly broken down.
The milder form of BMD is also caused by a defect in the dystrophin gene. It causes those affected to be able to produce dystrophin, but only in a shortened form with limited functional capacity, so that muscle fibers are gradually broken down here too, but much more slowly than in DMD.
The genetic defect is inherited X-linked
The dystrophin gene, which is defective in DMD and BMD, is located on the X chromosome, i.e. the sex chromosome. Women do not usually develop muscular dystrophy because they each have two X chromosomes in their body cells. This means that even if one of them is defective (i.e. carries the defective dystrophin gene), a second, healthy X chromosome is still present. It then usually takes over “command”, while the defective X chromosome remains inactive. In rare cases, however, functional inactivation of the healthy X chromosome can occur, so that around 5-10% of female gene carriers can develop symptoms of muscular dystrophy, which is usually mild, or a heart muscle disorder.
Women who carry the mutated dystrophin gene can pass on the defective X chromosome to their son: Boys (or men) each have an X chromosome from their mother and a Y chromosome – the male sex chromosome they inherited from their father – in their body cells. Because there is no second X chromosome as a healthy “alternative”, DMD always breaks out in boys if they have inherited the underlying genetic defect from their mother.
Symptoms: Duchenne muscular dystrophy
The progressive muscle atrophy in DMD primarily affects the pelvic and thigh muscles. With increasing age, the following symptoms are typical of the disease:
Symptoms of Becker-Kiener muscular dystrophy
The course of symptoms in BMD is milder and much slower than in DMD. For example, most sufferers usually retain their ability to walk into adulthood; if the onset is late, the ability to walk can even be retained for life. In contrast to DMD, the weakening of the skeletal muscles in the shoulder and pelvic area is sometimes not symmetrical, but is pronounced differently on the two sides of the body. In addition, instead of motor impairments, cardiac problems are more common in those affected. Sometimes only an isolated myocardial disease is observed.
Duchenne muscular dystrophy – diagnosis with us
- If DMD is suspected at our Neuromuscular Center, we will first ask the parents to describe the nature, severity and progression of their child’s symptoms. This gives us a picture of the person’s medical history (anamnesis). This is followed by various examinations:
- Physical examination. In addition to heart and lung function, we carefully check the condition and functionality of muscles, nerves and joints.
- They are particularly important if DMD is suspected. One focus is on the creatine kinase (CK value). This enzyme is normally found inside the muscle cells. If it can be detected in high concentrations in the blood, this indicates significant muscle damage, which reinforces the suspicion of DMD or BMD. Other blood values are also elevated in those affected. These include, for example, lactate dehydrogenase (LDH) – another enzyme that is released into the blood when muscle cells are damaged.
- This usually confirms the suspicion of DMD or BMD: In eight out of ten affected people, the underlying genetic defect can be detected on the X chromosome.
- If a reliable diagnosis cannot be made using genetic analysis, we also take a tissue sample from affected muscles to have it analyzed in the laboratory. Destroyed muscle fibers and greatly reduced or absent dystrophin in the tissue sample then confirm the suspected disease.
- Ultrasound examination of the muscles and electromyography, EMG. Both an ultrasound examination and the measurement of the electrical activity of the skeletal muscles via electrodes can be useful in the diagnosis of muscular dystrophy.
- Electrocardiography, ECG. It measures the electrical activity of the heart muscle using electrodes. This makes it possible to assess whether and to what extent the heart muscle is weakened in its function. This is particularly important after diagnosis in order to monitor the progression of Duchenne or Becker-Kiener muscular dystrophy.
- Echocardiography. Cardiac ultrasound shows the extent of the restriction of the pumping function of the left ventricle in the context of myocardial involvement in Duchenne muscular dystrophy and is used to guide drug therapy for heart failure.
- Lung function tests (spirometry, respiratory muscle strength measurements, cough test). The regular performance of lung function tests and respiratory muscle strength measurements allows the early detection of severe respiratory muscle weakness, which makes it possible to assess the probability of so-called hypoventilation. If lung function or coughing are severely impaired, further examinations (sleep tests) and the necessary therapies such as nocturnal ventilation via a mask and mechanical cough aids are used.
- Arterial blood gas analysis. This provides information about ventilation and gas exchange, among other things, and is used for early detection of respiratory failure and thus the need for long-term ventilation.
- Sleep examinations (polygraphy, transcutaneous capnometry). Since respiratory muscle weakness first becomes noticeable during sleep, the carbon dioxide cannot be exhaled sufficiently during sleep (hypoventilation) and sleep apnea also occurs more frequently in Duchenne muscular dystrophy, the sleep examination with measurement of nocturnal carbon dioxide and oxygen is an important part of the examinations.
Interdisciplinary Neuromuscular Center
As a specialized center, the USZ cares for the largest Swiss cohort of adults with muscular dystrophy and, as an interdisciplinary neuromuscular center, has a team of experts from the fields of pneumology, neurology and therapists who work closely with other specialist disciplines such as cardiology, gastroenterology and orthopaedics/paraplegia. There is also close cooperation with the Mathilde Escher Home, which specializes in the care and support of Duchenne muscular dystrophy and whose care concept works excellently in collaboration with the USZ.
Duchenne muscular dystrophy: prevention, early detection, prognosis
The genetic defect underlying DMD cannot be prevented. If you as a woman already have a son with DMD and are planning further children, genetic counseling and genetic testing during pregnancy may be useful. This is because half of the other sons could also develop muscular dystrophy. Half of your daughters could carry the genetic defect like you. Genetic testing of expectant mothers is possible from the tenth week of pregnancy. It can detect or rule out a genetic defect in the dystrophin gene in the unborn child with a high degree of certainty. It is also important that you, as a gene carrier, have a cardiological examination in order to be able to recognize and treat any heart muscle disease at an early stage.
If you are the sister of a Duchenne boy, genetic counseling and genetic analysis might also make sense. This can be used to find out whether you are a carrier of the genetic defect and whether genetic counseling for family planning and a cardiological examination are advisable for you.
Duchenne muscular dystrophy – course and prognosis
Duchenne muscular dystrophy progresses continuously. It is not to be expected that the symptoms will improve fundamentally or that the progression of the disease will pause for a longer period of time. Most of those affected used to die between the ages of 18 and 25 – usually from respiratory failure. Today, life expectancy is significantly higher (around 35 years) with a good quality of life thanks to long-term ventilation.
The prognosis for BMD is more favorable. Many sufferers do not lose their ability to walk until 25 to 30 years after the onset of the disease; some sufferers do not even lose their ability to walk for the rest of their lives. However, life expectancy can be limited, usually as a result of heart problems.
Self-help groups
The exchange with people who are affected by the same disease can be a great support in coping with the disease. Advice on finding a suitable self-help group is available from Selbsthilfe Zürich. Self-Help Zurich and the University Hospital Zurich are cooperation partners in the national project “Health literacy thanks to self-help-friendly hospitals”.
Duchenne muscular dystrophy: treatment is individually adapted
Therapy for Duchenne muscular dystrophy aims to maintain the remaining muscle strength of those affected for as long as possible and to manage disease-related problems (e.g. in everyday life) with aids, for example. In addition, factors that can worsen the course of the disease (e.g. obesity) should be treated and the treatment of heart problems is also very important.