Muscular Dystrophy

Muscular Dystrophy is a group of more than 30 genetic diseases that are characterized by the production of abnormal muscle proteins leading to progressive weakness and loss of muscle mass. There are various types of Muscular Dystrophy and the severity of symptoms, location, and age of occurrence vary between the various types. The most common form of muscular dystrophy is Duchenne Muscular Dystrophy (DMD). Duchenne Muscular Dystrophy primarily affects boys and is caused by the absence of dystrophin, a protein involved in maintaining skeletal muscle. Onset is at approximately 3 years of age and is progressive: the initial presentation is lower limb muscle weakness and gait impairment but eventually, there is loss of muscle strength in the upper limbs and impairment of the diaphragm and heart leading to cardiopulmonary failure.

Structure and Function

In the cytoplasm of normal skeletal muscle, there is a protein called dystrophin that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. Dystrophin plays an important role in cell signaling, muscle cell membrane stabilization, and the transmission of force from the contracting sarcomere to the muscle cell membrane. In Duchenne Muscular Dystrophy, dystrophin is absent. In Becker Muscular Dystrophy, dystrophin is present but in lower quantity compared to normal muscle cells.

A lack of dystrophin leads to necrosis and fibrosis of the muscle cells (Figure 1). On gross examination, healthy skeletal muscle tissue in Muscular Dystrophy is replaced with fibrous and fatty tissue. On microscopy, immunoblot preparations with stains for dystrophin will show absent dystrophin in Duchenne Muscular Dystrophy and decreased intensity of the signal in Becker Muscular Dystrophy due to the quantitative decrease in dystrophin.

Figure 1: Biopsy of the calf muscle from a person with Duchenne Muscular Dystrophy showing replacement of muscle fibers by fat cells.

The muscular dystrophies are genetic disorders which may be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive fashion. Duchenne Muscular Dystrophy is due to a point deletion causing a nonsense mutation in the gene which encodes the dystrophin protein. The result is an inability to produce dystrophin. This mutation is inherited in an X-linked recessive manner (Figure 2). Becker Muscular Dystrophy, also X-linked recessive, is due to a mutation in the non-coding region of the gene encoding dystrophin, which does not shift the translation reading frame like the Duchenne Muscular Dystrophy mutation. The mutation in Becker Muscular Dystrophy leads to the production of a truncated version of dystrophin, and smaller quantities of the protein are produced.

Figure 2: X-linked recessive transmission. (image modified from Wikipedia)

Patient Presentation

Duchenne Muscular Dystrophy generally presents between 3 and 6 years of age. The condition first affects muscles near the hip and shoulder, leading to difficulty in jumping, running, climbing stairs, and toe walking.

In most patients, the classically-described calf pseudohypertrophy may be seen. This phenomenon is due to fatty and fibrotic infiltration in the calf muscles. Increased lumbar lordosis may be present, as this compensates for the gluteal muscle weakness present (Figure 3).

Figure 3: A drawing of a 7-year-old boy with muscular dystrophy. Note the lower limb pseudohypertrophy, relative thinness of the arms and increased lumbar lordosis. (Image from Duchenne’s original manuscript)

To compensate for the muscle weakness first affecting the hip, when patients are rising from the floor, they will walk their hands up their legs and push their knees into extension to assist in standing themselves up. This maneuver is termed “Gower’s sign” (see Figure 4). If nearby objects such as tables, chairs or walls are present, patients may use these to achieve standing posture as well

Figure 4: Gower’s sign is seen when children with proximal muscle weakness stand up by first placing their hands on the ground and then walking towards their hands and pushing up along their own legs. Patients with weak lower limbs are able push up against their own bodies due to relative preservation of distal arm muscle strength. (Modified from

As patients age, the muscle weakness becomes more severe and progressive, leading to upper limb girdle weakness and trunk weakness which often results in scoliosis. Eventually, patients lose the ability to ambulate independently and will become wheelchair-bound by 10-15 years old. The progressive weakness leads to respiratory issues and often cardiomyopathies.

Symptoms in patients with Becker Muscular Dystrophy present later than those in Duchenne Muscular Dystrophy, often after age 7, due to a less severe disease course. Becker Muscular Dystrophy patients maintain ambulatory ability well into their teenage years.

Becker Muscular Dystrophy patients have a higher incidence of cardiomyopathy than those with Duchenne Muscular Dystrophy. Respiratory problems in Becker Muscular Dystrophy are also common, but occur later than Duchenne Muscular Dystrophy.

Objective Evidence

Elevated levels of creatine phosphokinase (CPK), leaking from damaged muscle, is a specific test for muscular dystrophy. Due to the abnormal muscle composition and progressive skeletal muscle breakdown, CPK levels in patients with Duchenne Muscular Dystrophy are elevated and can be as high as 200x normal values. Becker Muscular Dystrophy patients also show elevated CPK on lab testing, but levels are not as elevated as in Duchenne Muscular Dystrophy.

A muscle biopsy may also be taken for the purposes of diagnosis (as shown in Figure 1), but genetic tests are the more common route to diagnosis.

Genetic testing is available for detecting the abnormal gene which codes dystrophin. A polymerase chain reaction assay can detect deletions of the dystrophin gene.

When the child develops scoliosis, radiographs of the spine typically may show a long, C-shaped or S-shaped curve which may differ from the typical patterns seen in adolescent idiopathic scoliosis (Figure 5).

Figure 5: An anteroposterior radiograph of the spine in a patient with Duchenne Muscular Dystrophy showing a scoliosis with a characteristic long, sweeping S-shaped curve.


Because Duchenne Muscular Dystrophy and Becker Muscular Dystrophy are X-linked recessive, only male patients are affected, except in very rare cases (for fascinating reasons, including missing, damaged or inactivated second X chromosomes -- all beyond the scope of this text).

The incidence of Duchenne Muscular Dystrophy is one in 5,000 male live births. Becker Muscular Dystrophy is around 1/10th as rare, with an incidence of one in 30,000 male live births.

Differential Diagnosis

Differential diagnoses for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy include the other muscular dystrophies, such as limb girdle muscular dystrophy or myotonic muscular dystrophy. Other progressive neuromuscular conditions can have similar symptoms as Muscular Dystrophy, such as spinal muscular atrophy (SMA). One way to tell them apart clinically is that in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy, deep tendon reflexes are preserved, unlike in SMA. Guillain-Barre syndrome (GBS) can present with progressive weakness as well, but tends to progress faster. GBS also characteristically lacks deep tendon reflexes, and creatine phosphokinase levels will be normal.

Red Flags

  • Inability to climb, run, jump, or keep up with peers as a child should prompt investigation into Muscular Dystrophy.
  • Shortness of breath or murmurs necessitate a cardiac evaluation to rule out cardiomyopathy or respiratory failure.
  • The risk of malignant hyperthermia is increased in patients with Muscular Dystrophy. Vigilance of the anesthesia and surgical teams is required when patients are undergoing surgery.

Treatment Options and Outcomes

Corticosteroids may be used to treat children with progressive symptoms. Corticosteroid therapy has been shown to slow overall progression. It can delay the deterioration of ambulatory and lung function and can delay the progression of scoliosis. However, corticosteroid treatment is not without well-known side-effects, which include weight gain and Cushingoid appearance, osteonecrosis, headaches, cataracts, GI symptoms, and stunting of growth.

Supporting respiration during sleep with a ventilator has also been shown to lengthen lifespan in Muscular Dystrophy patients. In some patients, a tracheostomy may be required to facilitate this, but most individuals with Muscular Dystrophy can use Continuous Positive Airway Pressure (CPAP) or Bi-level Positive Airway Pressure (BIPAP) machines.

Physical therapy and orthotics also play a large role in the treatment of Muscular Dystrophy patients. Maintaining strength and range of motion may serve to prolong ambulation and prevent contracture formation. Targeted orthoses and braces may help maintain mobility and independence. When ambulatory function is lost, custom or adaptive equipment including a motorized wheelchair allows patients to maximize independence.

The degree of surgical treatment necessary for the care of patients with Muscular Dystrophy is still debated. Contracted joints (ankle plantarflexion contractures due to tight Achilles, knee contractures due to tight hamstrings, etc.) may be targets for surgical lengthening in an effort to prolong ambulatory ability, but the rehabilitation phase of surgical treatment must not be overlooked. Vigilance with early post-operative physical therapy is necessary to prevent deconditioning and limit the progress achieved by the surgical intervention itself.

The development of scoliosis is extremely common in this patient population, especially after ambulation is lost. Bracing should not be used in these patients – it does not prevent curve progression, and more importantly, may restrict pulmonary function in a patient with already tenuous pulmonary status.

A scoliosis measuring 20 to 30 degrees is usually an indication for posterior spinal fusion (with an anterior release sometimes added for severe, stiff curves). Often, fusion to the pelvis must be performed to correct pelvic obliquity. Rapid progression of the curve or severe restrictive lung disease (manifested as low forced vital capacity, the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible) are also used as indications for surgery.

The goals of surgical treatment in scoliosis for Muscular Dystrophy patients is to prevent further spine deformity, thus preventing further worsening of restrictive lung disease, and a balanced spine over a balanced pelvis to facilitate sitting posture, comfort, and care.

Patients with Duchenne Muscular Dystrophy may survive, on average, into their mid-20s. This life expectancy, however, is greatly dependent on the quality of care, with some patients who have access to excellent care and caregivers living into their 30s or even 40s.

The cause of death is usually respiratory failure, highlighting the need for appropriate respiratory care in these patients (including nighttime ventilation and well-timed spine fusion). Heart failure due to dilated cardiomyopathy is another common cause of death. Those with Becker Muscular Dystrophy, due to a milder and more delayed constellation of symptoms, live much longer.

Patients with Duchenne Muscular Dystrophy have a higher complication profile following surgical procedures. As mentioned above, malignant hyperthermia is common in these patients, and so appropriate steps must be taken by the anesthesia and surgical teams prior to operating.

Risk Factors and Prevention

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy are both genetic diseases inherited in an X-linked recessive manner. Thus, females who are carriers of the disease have a 50% chance of passing the disease on to their offspring. However, around 1/3rd of cases are due to a spontaneous mutation.


The gene which codes for Dystrophin is one of the longest, representing almost 0.1% of the entire human genome.

Although the condition now known as Duchenne Muscular Dystrophy was described by Giovanni Semmola in 1834 and Gaetano Conte in 1836, Duchenne Muscular Dystrophy is named after Guillame-Benjamin-Amand Duchenne, a French physician who described the condition in a series of patients. Notably, Duchenne was the first physician to perform a surgical biopsy, that is, taking tissue from a living patient for the purposes of diagnosis.

Since Duchenne Muscular Dystrophy and Becker Muscular Dystrophy are both due to mutations in a single, known gene, ongoing research is focused on targeted gene therapy in an effort to replace the mutated gene in affected individuals via a viral vector.

Key Terms

Duchenne muscular dystrophy, Becker muscular dystrophy, Dystrophin, Gower’s sign

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