Duchenne and Becker Muscular Dystrophy are conditions that lead to the progressive weakness and loss of function of certain muscles in the body.
Duchenne muscular dystrophy (DMD) is a disease that affects skeletal muscles, which are the muscles we use for movement, and cardiac (heart) muscle, which pumps blood through our body. People with DMD can develop muscle weakness as early as 3 years of age. The weakness first becomes apparent in the muscles of the thighs, hips, pelvis, and shoulders. Sometimes, children with the condition will find it hard to get up off the ground without using their hands to help them push off from the floor (this is also referred to as the Gower sign).
Children with DMD tend to fall more frequently than other children their age, and may have difficulty climbing stairs and running. Often, the calf muscles in their lower legs appear to be well-developed, but this is actually a result of the damaged muscle being replaced by fat and scar tissue (pseudohypertrophy). Many children with DMD gradually begin using a wheelchair to help conserve their energy when they need to travel a long distance; and, as their muscles weaken further, many children with DMD require a motorized wheelchair.
As the disease progresses, muscles in the arms and upper body weaken too, and special accommodations may be necessary. It is important to remember that DMD does not affect how nerves function, so children with this condition are still able to feel sensation (touch) in the affected areas of their body and the muscles of the bowel and bladder are not affected. However, some adolescents and adults with DMD can have gastrointestinal complications that require evaluation and treatment.
By the early teenage years, the muscle layer in the heart (myocardium) becomes weakened, which is called cardiomyopathy. This condition needs to be closely monitored by a cardiologist (heart specialist). Also, the muscles required for breathing, such as the diaphragm and other muscles, become weaker, making it harder to breathe and cough. Care by a pulmonologist would be indicated at that time. About 30% of children with DMD have a learning disability and may have a harder time focusing their attention and memorizing things at school. If this appears to be the case, children should be evaluated by a specialist so that they can be offered the proper resources.
Becker muscular dystrophy (BMD) is a milder form of DMD. People with BMD don’t usually develop muscle weakness until adolescence or early adulthood and their symptoms progress more slowly.
There is also a condition called DMD-associated dilated cardiomyopathy. People affected with this condition have progressive weakening of their heart muscle, but do not have severe weakness in the skeletal muscles, and they are able to walk independently; however, need to be closely followed by a cardiologist.
Both DMD and BMD are caused by changes in a gene called Dystrophin. This gene is in charge of making a protein, also called Dystrophin, that helps protect and make muscle fibers more stable. The protein may also send certain chemical messages within the muscle cell. Without this protein, muscles fibers become damaged each time they are used and gradually weaken and die, which leads to the muscle weakness and cardiomyopathy associated with the disease.
The genetic changes to the Dystrophin gene in people with BMD are less severe and allow some residual Dystrophin protein to be produced, which accounts for the different symptoms experienced by people with BMD.
Parents of children with DMD typically notice that their child is falling frequently and having difficulty walking up stairs and/or running. When these symptoms are shared with the pediatrician, he/she will perform a physical exam to check for signs of muscle weakness, and order some blood tests, which include measuring an enzyme called CK or creatine phosphokinase. This enzyme measures muscle damage and is extremely elevated in individuals with DMD/BMD. If the physical exam and CK levels are suggestive of DMD/BMD, genetic testing is recommended to examine the sequence of the Dystrophin gene to determine if there are changes in the gene that are affecting its ability to produce a fully functional Dystrophin protein.
Before the availability of genetic testing, diagnosis for DMD/BMD often required taking a sample of muscle from an individual (usually from their thigh muscle) and using special techniques to see how much Dystrophin was present in the muscle cells. Thanks to the widespread availability of genetic testing, most individuals are now able to achieve a diagnosis without a muscle biopsy.
Genetic testing is the gold standard to confirm the diagnosis of Duchenne and Becker Muscular Dystrophies. When a muscular dystrophy is suspected, genetic testing is essential to determine the exact form of muscular dystrophy. Prognosis, recommended surveillance, subspecialty involvement, recurrence risks, and available treatments vary for different forms of muscular dystrophies. In many cases, invasive testing and muscles biopsies may be avoided once a genetic diagnosis is made. By knowing the genetic diagnosis, treatment and management can be tailored to the patient.
To understand how Duchenne muscular dystrophy is inherited, it is important to remember some aspects of genetics. Our genetic information is contained in structures in our cells called chromosomes. Women have two X chromosomes (XX) and men have one X and one Y chromosome (XY). The Dystrophin gene is located on the X chromosome. DMD occurs in males when the Dystrophin gene on their X chromosome is not producing any functional Dystrophin protein. If the Dystrophin gene is producing an abnormal form of the Dystrophin protein or a reduced amount of protein, males will have BMD.
In contrast, since females have two X chromosomes, when the Dystrophin gene on one of their X chromosomes is not functioning correctly, they have a second copy of the Dystrophin gene on their second X chromosome that can still produce sufficient Dystrophin protein for proper muscle function. However, some women who carry a disease-causing change in one of their Dystrophin genes can show some signs of muscle weakness and should be monitored for cardiomyopathy. These females are known as manifesting carriers, because they manifest some of the symptoms of the disease.
The changes in the Dystrophin gene that cause Duchenne and Becker muscular dystrophies can be inherited from a female carrier and passed on to her affected son, or can be caused by a new change in the Dystrophin gene that occurred in a single egg cell that was fertilized (also known as a de novo change), or by the fertilization of an egg cell from a small population of egg cells that have genetic changes in the Dystrophin gene (gonadal mosaicism). About one third of the cases of DMD/BMD are due to a de novo change, while about 10% of the cases are thought to be due to gonadal mosaicism. Genetic testing of the Dystrophin gene for mothers of affected sons can help to distinguish between these possibilities. Meeting with a genetic counselor is strongly recommended so that the family can determine the cause of the condition and which other family members may also be at risk.
The symptoms of Duchenne and Becker muscular dystrophy are managed through close surveillance and collaboration between medical specialists in genetics, orthopedics, cardiology, occupational, physical therapy, and pulmonology, who work together to meet the needs of the child. Ideally, individuals with DMD/BMD can be cared for at a multidisciplinary clinic that specializes in muscular dystrophy. For some individuals, the use of corticosteroids can be helpful in slowing disease progression, but such use has to be balanced against the side effects caused by the medications. The Muscular Dystrophy Association has detailed information regarding management recommendations for Duchenne muscular dystrophy, entitled: Diagnosis and management of Duchenne muscular dystrophy. The Muscular Dystrophy Association is also an excellent resource to stay up-to-date regarding new medications and treatments that may become available. Recently, a drug called eteplirsen has become available for some individuals with Duchenne muscular dystrophy.
“The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children and the lack of available therapy.”
Families can also search www.clinicaltrials.gov to monitor for clinical trials that may become available for Duchenne and Becker muscular dystrophy. These are research-based trials that are conducted to measure the effectiveness of new treatments and medications. You should always discuss any clinical trial with your physician prior to participating.
Your physician will assist you in identifying and arranging for the appropriate genetic test(s). If you have specific questions or concerns about the testing, your physician may refer you to a genetic counselor to discuss further. Once you are ready to proceed with genetic testing, you will need to submit either a blood or saliva sample.