Medical Awareness >>   Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy (DMD)


Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. It is the most common hereditary neuromuscular disease and it is not limited to any race or socioeconomic group. Mutations in the gene named dystrophin led to progressive muscle fibre degeneration or damage and weakness. This weakness may see initially with difficulty in movement and patients unable to perform day-to-day activities and bound to use wheelchairs. Generally, there are cardiac and orthopaedic complications occur and death normally seen in the twenties because of respiratory muscle weakness or cardiomyopathy. Presently, the treatment with glucocorticoids and physiotherapy are implicated to prevent orthopaedic complications. 

About Duchenne Muscular Dystrophy | EspeRare Foundation

Causative factors

In DMD there is a mutation of the dystrophin gene, which is located on chromosome Xp21. It is inherited as an X- linked recessive trait; although, approximately 30% of cases are due to new mutation changes. 

Mutations in the dystrophin gene cause the diseases known as dystrophinopathies, which encircles Duchenne muscular dystrophy, Becker muscular dystrophy, and an intermediate form. Mutations results in limited production of the dystrophin protein, which leads to degeneration of the myofiber membrane continuity with repetitive cycles of cell death and regeneration. Fibrous tissues and adipose tissue (fat) gradually replace muscle leading to the appearance of symptoms.

Duchenne muscular dystrophy

Carrier females do not show any evidence of muscular weakness or symptoms. Around 20% of female carriers may be affected. 

Female carriers can show or come up with symptoms if they are associated with Turner syndrome (45X).

Most of the mutations are deletions and duplications, and this covers 70% to 80% of the mutations. 

Dystrophin is found in the cardiac muscle, also in the striated muscle, brain and retina. Its presence in the brain is less than in muscles; however, this does explain some of the central nervous system manifestations of this disease. 

What is Duchenne muscular dystrophy? - Parent Project MD

Incidence and Prevalence 

As DMD is an inherited, X-linked recessive disorder, boys are more frequently affected than girls. It is one of the most prevalent and most severe congenital myopathies.

Pathology and Physiology of DMD

Dystrophin is a large sized protein that facilitates interactions between the cytoskeleton, cell membrane, and extracellular matrix. Dystrophin is a crucial part of the dystrophin-glycoprotein complex (DGC), which has an important role as a structural unit of muscle. In DMD, dystrophin and DGC both proteins are missing, leading to excessive membrane fragility and permeability, dysregulation of calcium homeostasis, and oxidative damage. These factors have an important role in muscle cell necrosis. In patients with DMD age, the regeneration power of the muscles will not that active or appear exhausted, and connective and adipose tissue gradually replaces muscle fibres.

Histological examination

A muscle biopsy examination will demonstrate endomysia connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fibre necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat.

History and Physical development

Growth and development in the first few years of life are typically normal, with milestones achieved at a slightly delayed if not normal rate. Growth velocity, however, is slower, leading to short stature. Mild hypotonia in an infant may be seen, and poor control of the head in an infant may be an early sign. Weakness and difficulty in movement typically first occurred between 2 and three years of life. This manifests as toe walking, difficulty running, climbing upstairs, and frequently falling. Weakness of muscle is more prominent in proximal than distal muscles and in the legs more than in the forearms.

In patients who can do movements, increased chances of fractures have been seen as a result of the frequent falls.

Hardness in the ankles, knees, hips, and elbows may be seen.

Weakness of pharyngeal muscle can result in episodes of aspiration, nasal regurgitation of liquids, and a nasal quality of voice.

The absence of control on urine and stools due to urethral and anal sphincter weakness is not common and, if it is present, the manifestation is late.

Rarely, malignant hyperthermia after anaesthesia may be a presenting sign.

Symptomatic female carriers can show early onset of symptoms and progressive muscular dystrophy.

Intellectual impairment

Intellectual disability is seen in all patients; Although, only 20% - 30% of patients have an intelligence quotient (IQ) less than 70. The degree of impairment does not correlate with disease severity. Most of the patients have only a minimal form of learning disability and can function in a regular classroom. Epilepsy is more common than in the general population, and uncommonly, autism-like behaviour has been described.

DMD- Association with Cardiomyopathy

The symptoms of cardiomyopathy can develop in the early teens and are present in almost all patients in their twenties. Persistent tachycardia and heart failure may be present signs. As the disease progresses, fibrosis can extend to the left ventricle. Arrhythmias, are also related to the development of cardiomyopathy.

Physical examination reveals pseudo/false hypertrophy of the calf muscle. It has been seen that children take support of their arms to lift themselves from a seated position on the ground. This sign is known as the Gowers sign.


A dystrophinopathy should be suspected in patients with symptoms of weakness, a characteristic physical exam, and a possible family history of the disease. Laboratory investigation involves creatinine kinase measurements, muscle biopsies, gene testing, and ECG findings for cardiomyopathy

Muscle Biopsy

A muscle biopsy will demonstrate endomysial connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fibre necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat.

Gene Analysis

Patients with DMD disorder, demonstrate the complete or near-complete absence of the dystrophin gene. Dystrophin immunoblotting can be considered to predict the severity of the disease. In DMD, patients are found to have less than 5% of the normal quantity of dystrophin. Polymerase chain reactions (PCR) can also be used.

Dystrophin immunocytochemistry can also be sued to detect cases not identified by PCR.

Electrocardiogram (ECG)

Supraventricular arrhythmias are more common. intra-atrial conduction abnormalities are more common than AV or infra-nodal defects in DMD.


Evidence of dilated cardiomyopathy is present in almost all patients by the end of their teens or in their 20s.


To date there is no medical cure exists for this congenital dystrophy, and the disease has a poor prognosis. Treatment is limited to glucocorticoid therapy, prevention of contractures, and medical care for cardiomyopathy and respiratory compromise. 

Glucocorticoid Therapy

Treatment with glucocorticoid decreases the rate of apoptosis and can reduce myofiber necrosis. Prednisone is advisable in patients four years and older in whom muscle activity is declining or plateauing.

Prednisone is advisable.

Research has shown that glucocorticoid intervention is associated with improved pulmonary activity, late appearance of scoliosis reduces incidence and development of cardiomyopathy and overall improved mortality.


Treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers is advisable. Initial studies showed that early treatment with ACE inhibitors may slow the progression of the disease and prevent the onset of heart failure.

Overt heart failure is treated with digoxins and diuretics as in other patients with cardiomyopathy.

Observation comprises a cardiology investigation with ECG and echocardiogram. This should be implemented at the time of diagnosis or by the age of 6 years. Routine observation should be indicated once every two years until the age of 10 and then yearly after that. If there is evidence of cardiomyopathy is present, a check-up/observation every six months is indicated.

Pulmonary Interventions

The pulmonary function must be tested prior to the exclusive use of a wheelchair. This should be repeated twice a year once the patient reaches 12 years of age, must use a wheelchair or vital capacity is found to be less than 80% of predicted.

Orthopaedic Interventions

Physiotherapy to prevent contractures is the mainstay of orthopaedic interventions. According to the patient’s need, passive stretching exercises maybe consider. Surgery may be required to release contractures for advanced disease. 


Patients are at risk for malnutrition, including obesity. Supplement of vitamin D and calcium is advisable to prevent osteoporosis secondary to chronic steroid use. At the age of 3 DEXA scanning is advisable and then repeats the same every year.

Physical activity/Exercise

Every patient with DMD should adopt a routine of gentle exercise to prevent disuse atrophy. Physical activity has to be reduced when there is muscle pain initiated. 

Novel Therapies

In gene therapies, there are medicines that combine with RNA and skip over the unwanted codon. This generates a shorter but potentially active/functional protein. Eteplirsen medicine is used for this therapy. Eteplirsen is approved by FDA for this therapy.


Generally, the prognosis is very poor for the patient with DMD. Patients need to start using wheelchairs by the age of 12 years. Due to respiratory or cardiac complications, death occurs in the teens or 20s. Another reason for death is airway obstruction and pneumonia.