Duchenne type muscular dystrophy is a malignant (malignant) muscle disease caused by a genetic defect on the X chromosome, so the disease can only occur in male offspring. Symptoms appear as early as infancy in the form of weaknesses in the pelvic and thigh muscles. It is always fatal in early adulthood due to degeneration of the heart and lung muscles.
What is Duchenne type muscular dystrophy?
Duchenne type muscular dystrophy (DMD) is a progressive muscle weakness caused by a gene defect on the “male” X chromosome. Because the gene defect is located on the X chromosome, the disease can only occur in male family members. For these, however, it is homozygous because the gene on whose mutation the disease is based occurs only once and cannot be compensated for by a second gene – as is usually the case with a diploid chromosome set. This means that male offspring will almost certainly develop DMD if the gene defect is present. DMD is manifested early in life between the first and sixth year by muscle weakness and muscle wasting in the pelvic and leg muscles. The disease itself is triggered by a synthesis disorder of the protein dystrophin. Dystrophin is an important and functionally essential component of the membrane surrounding muscle fibers (sarcolemma). DMD is the most common form of all known muscular dystrophies.
Causes
The so-called DMD gene, which is responsible for encoding the protein dystrophin, is located on the X chromosome. With 2.5 million base pairs, it is the largest known gene in the human genome and is therefore susceptible to mutations, the effect of which is usually to completely prevent synthesis of dystrophin. Mutation of DMD gene may be loss (deletion) of a fragment (several base pairs), duplication or point mutation, in which only a single nucleic base is affected. The mutations cause various forms of muscle weakness, of which Duchenne muscular dystrophy is by far the most common manifestation. It is remarkable that in about one third of the boys suffering from DMD, the disease was caused by a new mutation and not inherited from the mother. This explains why DMD does not decrease significantly in the frequency of its occurrence.
Symptoms, complaints, and signs
Duchenne muscular dystrophy type (DMD) manifests in the first few years of life and has its onset in the pelvic girdle area. Infants have trouble walking, walk unsteadily, stumble, and fall more often. They are unable to walk quickly. Furthermore, due to the weakened thigh muscles, they are unable to stand up on their own, but support themselves with their hands on the thigh when standing up. This characteristic symptom is also known as Gowers’ sign. People with Duchenne muscular dystrophy (DMD) show an increase in connective and fatty tissue, especially in the calves. This is why their calves appear unusually strong. In medical terminology, the thickened calves are called gnome calves. Furthermore, patients with Duchenne muscular dystrophy (DMD) have pointed feet and a pronounced curvature of the spine in the lumbar region. Duchenne muscular dystrophy (DMD) progresses rapidly, so that a large proportion of patients are dependent on wheelchairs and full-time nursing care before the age of 12. In the advanced stages of the disease, weakness of the respiratory muscles causes breathing difficulties. Furthermore, those affected have diminished reflexes and suffer from sensory disturbances. Approximately one-third of patients further exhibit a reduction in intelligence.
Diagnosis and course of the disease
If the initial suspicion is confirmed, neurological examinations and functional tests of the musculature are indicated. Imaging techniques such as MRI and ultrasound may also provide further information. Often, an elevated level of the muscle enzyme creatine kinase can be detected in the blood. Ultimately, genetic diagnostics provide certainty, which also allows the assignment of the muscular dystrophy to one of the known manifestations. The course of DMD is progressive. From the age of 5 to 7, those affected are usually no longer able to stand up from a sitting or lying position without assistance and are no longer able to climb stairs.The muscle atrophy leads to deformities of the joints and to deposits of fatty tissue in the muscles to replace the muscle tissue. As a rule, children are dependent on a wheelchair from the age of 10 to 12. Life expectancy is about 40 years, although even earlier death before the onset of puberty cannot always be prevented.
Complications
As a rule, muscular dystrophy type Duchenne causes the death of the patient. In this case, death occurs at a very young age. Especially parents and relatives are affected by severe psychological discomfort and upset due to the disease. Due to the disease itself, the patients suffer from a very weakened musculature. This weakening takes place in the entire body, so that also internal organs and also the heart are weakened. Eventually, cardiac death results. Likewise, ordinary activities are difficult for the affected person to perform and the patients suffer from a very low resilience. It is not uncommon for patients to become dependent on the help of other people in their daily lives. Joints and muscles are often deformed and there are considerable movement restrictions due to Duchenne muscular dystrophy. Likewise, this disease can also lead to psychological complaints and thus significantly reduce the patient’s quality of life. There is no treatment for Duchenne muscular dystrophy. Patients are dependent on various therapies to increase their life expectancy, which is, however, greatly reduced. However, no particular complications occur during treatment.
When should one go to the doctor?
A doctor should be consulted if there are disturbances in muscle strength, reduced physical performance or muscle tension. If irregularities already occur in the development and growth process in direct comparison to peers, a visit to the doctor is advisable. If there is low resilience or rapid fatigue, consultation with a doctor is recommended. Deformities of the physique, poor posture of the upper body or general incorrect loading of the skeletal system should be examined and treated. Curvature of the spine is characteristic of Duchenne type muscular dystrophy and should be discussed with a physician immediately. In case of disturbances of respiratory activity, shortness of breath or interruptions of breathing, a physician is needed. In case of acute respiratory impairment or oxygen deficiency, immediate action is required. Indications are a blue coloration of the lips and fingers, loss of consciousness, and internal weakness. In severe cases, an ambulance should be alerted. Until their arrival, the affected person requires mouth-to-mouth resuscitation. If the affected person suffers from sensory or perceptual disturbances of the skin, this is a sign of an existing irregularity. It should be clarified so that treatment can alleviate the symptoms. In the case of a conspicuousness of the mental potential, a supposed decrease in intelligence as well as a learning disability, a visit to the doctor is advisable.
Treatment and therapy
To date, AMD is not curable. All attempts at gene therapy have been unsuccessful and probably failed because of the body’s own immune system. For several years, drugs have been in development or even already in experimental testing that are intended to mitigate the effects of the genetic defect on dystrophin synthesis, allowing the body to synthesize dystrophin again, at least to a limited extent. One drug currently in clinical trials is eteplirsen, also known as AVI-4658. Another drug in the experimental phase is ataluren. In the presence of so-called nonsense mutations, which cause the transcription of base sequences to be aborted due to so-called stop codons, ataluren should be able to prevent the abortion of transcription. If successful, this means that the body would again be able to synthesize dystrophin, thereby halting the muscular dystrophy. The therapies currently used are aimed at alleviating symptoms and include life-prolonging measures, but do not address the actual cause of the disease. The catalog of measures for symptom control consists of a mix of medical care, physiotherapy and occupational therapy, as well as nursing care and psychological support for patients and their relatives. As the disease progresses, breathing aids via oxygen masks are necessary.In later stages, an incision into the trachea (tracheostomy) is usually necessary to provide active ventilation.
Outlook and prognosis
For Duchenne-type muscular dystrophy, a cure is not yet possible today. The disease is characterized by a characteristic course and usually has the same prognosis in all affected individuals. Between about the third and fifth year of life, slight muscle weakness in the legs becomes noticeable. Subsequently, the atrophy of the thigh and pelvic muscles progresses steadily, with connective and fatty tissue replacing the gradually dwindling muscle tissue. Later, the musculature of the shoulders and arms is also affected by muscular dystrophy. Between the ages of five and seven, affected children are already dependent on constant help to get up from a lying or sitting position. Many of the affected children with Duchenne muscular dystrophy completely lose the ability to walk already in their twelfth year, which leads to the fact that they can no longer manage without a wheelchair. In the further course of the disease, however, the affected persons can initially still care for themselves, albeit to a limited extent. In most cases, however, patients are then dependent on complete care from family members from the age of 18. Finally, Duchenne muscular dystrophy also affects the respiratory muscles and the heart muscle of the affected persons, which reduces their life expectancy. As the disease progresses, it almost always leads to death by suffocation or heart failure.
Prevention
Because muscular dystrophy AMD is caused by a genetic defect, direct preventive measures that might provide protection against the onset of the disease are not known. However, early diagnosis, preferably in the 1st or 2nd year of life, helps to control and delay the symptoms via a wide range of therapeutic measures. In addition to nutrition and providing the body with minerals, amino acids, vitamins, enzymes, and trace elements, targeted physical therapy is important to maintain muscle function as long as possible.
Aftercare
In Duchenne muscular dystrophy, the options for direct aftercare are usually significantly limited or, in some cases, not available to the patient at all. For this reason, the affected person should ideally see a doctor at an early stage to avoid the occurrence of other symptoms or complications. It is not possible for the condition to heal itself, so a visit to a doctor is usually necessary. Most patients are dependent on help and care from their own family in everyday life. The affected persons must be relieved, whereby efforts or stressful and physical activities are generally to be avoided. Psychological support is often also important in order to prevent the occurrence of depression and other psychological upsets. Furthermore, in Duchenne muscular dystrophy, physiotherapy measures are also necessary to alleviate and limit the symptoms. Many of the exercises can also be repeated in the patient’s own home to further alleviate the symptoms. Further measures of aftercare are usually not available to the affected person with this disease. Possibly, the muscular dystrophy type Duchenne thereby also reduces the life expectancy of the patient.
What you can do yourself
For those who live with Duchenne muscular dystrophy, assistive devices are very important. They increase the quality of life, make everyday life easier and support participation in society. It is therefore all the more important to be well informed about which aids are possible and what options there are for fitting them. In the late ambulatory and non-ambulatory phases, additional aids may be required to manage everyday situations such as eating and drinking as well as personal hygiene. Aids trade fairs, where manufacturers present their products, are an excellent source of information. There you get a good overview of which aids come into question. In addition, the contact to other families affected by Duchenne muscular dystrophy or other muscle diseases can be helpful. The German Society for Muscular Dystrophy offers a comprehensive range of advice and supports parents in establishing contact with other people affected.If the affected child has not been dependent on the wheelchair for long, wheelchair training can be helpful at the beginning, in which the correct handling of the wheelchair is learned. Stretching the muscles and maintaining joint mobility are important prerequisites for keeping the limbs functional for as long as possible. In many cases, daily stretching exercises with family support are essential in addition to physical therapy.
