Duchenne Muscular Dystrophy


About Duchenne muscular dystrophy

It has been estimated that one person in every 3,000 has a serious disabling inherited neuromuscular disorder. Most neuromuscular diseases are incurable. For many it is a devastating disease that results in muscle wasting, loss of mobility, breathing difficulties and early death. For many parents a diagnosis is like a death sentence.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder affecting approximately 1 in 3,500 live male births (less in females) causing death in the late teens or early twenties. It is a genetic disease resulting from a mutation in a gene on the X-chromosome known as the dystrophin gene. The dystrophin gene is the largest gene in the human body which means that it has a high rate of spontaneous mutations. Consequently, one in three cases of DMD result from novel mutations without any previous family history.


What causes Duchenne muscular dystrophy?

Within our gene makeup, there is an important muscle protein called dystrophin, which is one of the largest genes found to date. Dystrophin acts as the glue that holds muscles together. Without dystrophin, muscles are not able to operate properly and will eventually suffer progressive damage.

When a child is diagnosed with DMD, his body is not able to produce any dystrophin. Without dystrophin, muscle cells within the body gradually weaken and eventually die.


What is Dystrophin?

Each gene codes for a specific and unique protein. These proteins build the body, and keep it running smoothly. There are thought to be roughly 100,000 genes in each human, and as many proteins. Dystrophin is only one of them. In DMD, the gene that codes for dystrophin mutates and the body is unable to produce this protein.

Dystrophin's main function is to serve as a "connector" in the cell's structural support system. When dystrophin is faulty, two things happen. First, muscles cannot contract normally, which leads to weakness. Second, as a muscle cell contracts, its delicate membrane tears, spilling the contents of the cell into the surrounding fluid.

Not only do vital substances leak out of muscle fibers, but harmful substances pour in. As with any injury to the body, immune cells arrive to remove the damaged cells. The injured muscle cells are "cleared away" and are replaced with hard, fibrous or rubbery scar tissue.


How is Duchenne muscular dystrophy diagnosed?

DMD is typically diagnosed in children between the ages of 3 and 7. Usually parents will notice that their child is behind other kids their age in developmental milestones. Young children may appear to be clumsy and will often fall down during regular activity. Climbing stairs, running, and rising up from the floor become very difficult.

The following tests are used to diagnose Duchenne muscular dystrophy;

Creatine Kinase
The body creates an enzyme called creatine kinase (CK) that normally lives inside muscles. When muscles are functioning normally, CK levels in the bloodstream are relatively low. But when muscles are damaged, the muscle cells split open, causing their contents to spill out into the bloodstream. This creates a rise in the levels of CK in the blood. Measuring CK levels verifies that there has been muscle damage.

Muscle Biopsy
In order to determine the cause of the muscle damage, doctors may perform a muscle biopsy. A surgeon removes a small sample of muscle and examines it under a microscope to see if dystrophin is present.

DNA testing
DNA is obtained from a blood sample and scientists are able to examine the dystrophin gene to find out exactly where the mutation has occurred.


Symptoms of Duchenne

The progression of symptoms (in order of occurrence) are:

Weakness and fatigue can be symptoms of DMD. Due to the additional effort that children with DMD put forth when climbing stairs, running or even standing, they will often grow weak from these routine tasks.

Tightening of joints and tendons is another symptom boys with DMD may suffer from. This is called contracture. It typically affects the ankles first, followed by the hips and knees, and finally, the joints of the upper limbs. Physical therapy is used to help offset this.

Scoliosis is a curvature of the spine. If severe, scoliosis can be disfiguring and eventually limit the function of the lungs and upper limbs. Young men who have DMD often require surgery to help straighten their spines. In this major operation, doctors insert a metal rod to keep the spine straight.

Speech, behavioural, and cognitive deficits are more common in children who have DMD due to dystrophin abnormalities in the brain. About one third of young children with DMD have some degree of a learning disability. Unlike progressive muscle weakness, when a learning disability does occur in a boy with DMD, it does not worsens as time goes on.

As children with DMD grow into teenagers, respiratory muscle function may begin to decline enough to change the way lungs pull air in and push it out. As DMD progresses, the diaphragm becomes weakened and breathing becomes more difficult. At the same time, muscles responsible for coughing are also growing weaker and are not able to support the diaphragm. This may allow a simple cold to quickly progress into pneumonia in young men with DMD.

During the teen years, children with DMD will often develop heart problems as the muscle layer of the heart begins to deteriorate. This puts the young men at risk of a heart attack.