Duchenne muscular dystrophy (DMD) is the most common progressive muscle disease in childhood and affects (almost) only boys. Approximately one in 3500 male newborns is affected (1:3500). The disease leads to progressive muscle atrophy in early childhood, with boys requiring a wheelchair from the age of 10 to 12.
Below you will find further information and selected specialists in clinics for Duchenne muscular dystrophy.
Duchenne muscular dystrophy is caused by a mutation in the so-called dystrophin gene. Inheritance is X-linked recessive, i.e. the disease almost exclusively affects boys.
Von Kuebi = Armin Kübelbeck - own work. people sketches taken from Image:Autorecessive.svg made by en:User:Cburnett. Idiograms taken from Chromosome Y.svg and Chromosome X.svg bothe made by en:User:Mysid. Made with InkScape. PNG file derived from SVG master file, CC BY-SA 3.0, Link
In 2/3 of cases, the defective gene is inherited from the mother to her son. As the mother herself has two X chromosomes, the disease usually does not manifest itself in her (conductor) or only in mild heart failure, which often remains undetected until her son is diagnosed.
In 1/3 of cases, the disease is not inherited but is caused by a new mutation (de novo mutation).
The genetic defect means that the protein dystrophin, which is important for the muscle membrane, cannot be produced. The cell wall of the muscles becomes unstable and triggers progressive muscle wasting.
The first symptom of Duchenne muscular dystrophy is often a delay in learning to walk freely. However, some of the affected boys do not show any recognizable motor problems in the first 1 to 2 years of life.
Delayed speech development is observed disproportionately often in boys with normal mental development. The motor problems begin at kindergarten age. Boys fall down more often than other children. Their stamina for longer walking distances also decreases and they are more clumsy than their peers in terms of motor skills.
Seemingly contradictory to the motor problems are the strikingly strong calves of the boys. However, this is not due to an increase in muscle mass, but to a connective tissue remodeling of the muscles with fat storage ('pseudohypertrophy'). The boys have increasing problems getting up from the floor. If they have nowhere to hold on to, they lean on their thighs when standing up (positive 'Gowers sign').
The boys develop a so-called 'waddling gait' (positive Trendelenburg's sign), a pronounced hollow back due to weakness of the abdominal and back muscles and increasing muscle contractures. This is a reduced joint mobility due to shortened tendons. Between the ages of 10 and 12, boys are usually no longer able to walk more than a few steps and are dependent on a wheelchair.
As the disease progresses, increasing weakness of the arm muscles becomes apparent and the muscle weakness leads to a curvature of the spine(scoliosis). Other organ systems affected at a later stage are the heart (possible weakness of the pumping function) and the respiratory muscles.
A suspected diagnosis can be made on the basis of the typical clinical signs (male sex, muscle weakness, calf hypertrophy, waddling gait). The first step is to determine the level of the muscle enzyme creatine kinase (CK) in the blood . This value is very high in Duchenne muscular dystrophy. In the past, the next step was an EMG examination and a muscle biopsy. Nowadays, the diagnosis can be confirmed directly by means of a genetic test.
There is still no cure for Duchenne muscular dystrophy. However, numerous studies are underway in which various treatment approaches are being tested in animal models and already in clinical trials (including exon skipping, gene therapy, utrophin upregulation, myostatin inhibition). In the meantime, the first active substance has been approved (ataluren). However, this is only effective in the case of a specific mutation (gene change). This is a so-called nonsense mutation, which is only present in approx. 13 percent of all Duchenne patients.
Even without a causal therapy, there are various important treatment approaches. These are initially aimed at maintaining the declining muscle strength for as long as possible and preventing joint contractures. In addition to regular physiotherapy, the boys often receive treatment with corticosteroids, which leads to an increase in walking ability of around 2 years.
Other important measures relate to weight, heart and lung function, the provision of aids adapted to the patient's everyday needs, as well as school issues and social care. An international group of experts has drawn up a corresponding concept for treatment standards(www.treat-nmd.de).
In the further course of treatment of Duchenne muscular dystrophy, various other specialists are involved in addition to the pediatric neurologist, such as cardiologists, pulmonologists and orthopedists, as well as therapists such as physiotherapists, and in some cases (usually at a younger age) occupational therapists and speech therapists.
The average life expectancy of patients has increased significantly from just under 20 years in the past due to the new possibilities of (sometimes only nocturnal) ventilation and scoliosis surgery. With stable cardiac findings, a life expectancy into the 4th decade of life is possible. However, patients unfortunately have to cope with significant restrictions in their quality of life.
