Neuromuscular conditions affect how our muscles function or the way in which our nerves communicate with our muscles. In order to perform “voluntary functions” like moving our arms or legs, a message needs to be sent from the brain through the nerves to tell the muscle to contract or relax. When the nerves do not function properly, or the muscle cells are too damaged to respond, a neuromuscular condition results.Primary symptoms are weakening and wasting of the skeletal muscles. However, other symptoms occur such as twitching, cramps, pain, movement problems, damage to the heart muscle, and weakening or discoordination of the muscles that affect the ability to breathe and swallow. Neuromuscular conditions can also cause muscle weakness that gets worse with physical activity, eyelids that droop, and double vision. Some examples of neuromuscular conditions include: muscular dystrophies, inherited myopathies, and congenital myasthenic syndrome.
Muscular dystrophies cause weakness and loss of function of various muscles in the body. In some forms of muscular dystrophy, skeletal muscles are primarily affected. Skeletal muscles are muscles in our bodies that are connected to the bones of our skeleton. However, some forms of muscular dystrophy can also affect the heart muscle and the muscles that work together to help us breathe and swallow. There are even some forms of muscular dystrophy that can affect vision, hearing, digestion, and brain function.
Inherited myopathies also cause muscle weakness, affect the ability of our skeletal muscles to function properly, and some forms can affect the heart muscle and the muscles required for breathing. Along with muscle weakness, individuals with certain forms of myopathy may also experience muscle cramps, stiffness, and twitching or spasms. Different forms of myopathies develop at different ages with unique symptoms. For instance, congenital myopathies are apparent at birth, while other forms of myopathies may not become apparent until adulthood. The various forms of myopathies are sometimes distinguished from each other based on specific changes in the muscle tissue that can be seen when the muscle is carefully examined using special techniques under a microscope. Some of these findings are known as: central cores, central nuclei, fiber-type disproportion, multiminicores, and nemaline bodies.
Congenital myasthenic syndromes are another group of neuromuscular conditions that affect the communication between the nerves and muscles. Severe forms of these syndromes cause symptoms that are apparent at birth. These symptoms can include difficulty feeding, choking, difficulty breathing, drooping eyelids, and muscle weakness that worsens with physical activity. Some forms of the condition can be accompanied by stiffness or contracture of various joints throughout the body, known as arthrogryposis, which limits the range of motion of the joint. Symptoms may become apparent during adolescence or adulthood for more mild forms of congenital myasthenic syndromes. These syndromes do not typically affect the heart muscle.
Many neuromuscular conditions are caused by genetic changes that affect various aspects of muscle and nerve formation, function and communication. Because the symptoms of many neuromuscular conditions can be similar, it is very important to determine the specific diagnosis of the affected person, so that medical care can be specially tailored to their needs.
The diagnosis of neuromuscular conditions requires a careful review of the affected person’s medical history and a thorough physical exam by a physician who specializes in treating people with neuromuscular conditions. These steps are often followed by additional tests. One such test measures the level of an enzyme (creatine phosphokinase) in the blood. This enzyme is very elevated in certain conditions that cause muscle damage. Nerve conduction velocity tests and/or electromyography can be used to better understand how the condition is affecting the person’s nerve function. Muscle biopsies, that involve surgically removing a small sample of muscle from an affected person’s thigh and examining the muscle cells under a microscope can also be helpful in determining a diagnosis. More recently, however, comprehensive genetic testing for neuromuscular conditions has become available and can often be used earlier in the diagnostic process to reduce the need for more painful and invasive tests.
Comprehensive genetic testing for neuromuscular conditions can test for multiple types of muscular dystrophies, inherited myopathies, and congenital myasthenic syndromes in a single test. This is a tremendous advantage over testing for one condition at a time, or undergoing more invasive test methods (i.e. nerve conduction velocity, muscle biopsy) to achieve a diagnosis. Once a genetic diagnosis is determined, that information can be used to determine the best treatment plan for the affected person, can help to better predict the course of the disease and can help the family monitor and prepare for any complications associated with the diagnosis. Results of genetic testing can also be used to determine the risks for other family members to be affected with the same condition and their risks to have an affected child. Please speak with your clinician to understand the appropriate role of genetic testing in your diagnosis.
Currently, there is not a cure for most inherited neuromuscular conditions, however, the treatment options are improving and there are ongoing studies for many conditions and approved drugs in some cases. Symptoms of the conditions are managed through close surveillance and collaboration between medical specialists in genetics, orthopedics, cardiology, occupational and physical therapy, and pulmonology, who work together to meet the needs of the affected individual. Ideally, individuals with neuromuscular conditions can be cared for at a multidisciplinary clinic that specializes in those conditions.
The use of corticosteroids has been found to be helpful in slowing disease progression, in some forms of muscular dystrophy, but such use has to be balanced against the side effects caused by the medications. Recently, a drug called eteplirsen has become available for some individuals with Duchenne muscular dystrophy. Although the drug cannot cure the condition, it may slow the progression of symptoms.
As researchers and physicians continue to learn more about neuromuscular conditions, it will be essential to know an affected individual’s genetic diagnosis. Medications will become available over time that will be targeted to specific genotypes. Already, certain medications are recommended for some forms congenital myasthenic syndromes that should not be used for others. For instance, some individuals with slow-channel congenital myasthenic syndrome are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency.
A drug approved for patients with Duchenne muscular dystrophy requires that genetic testing has been done as it is only appropriate for patients with certain genetic changes in their Dystrophin gene. Ultimately, a person’s specific genetic diagnosis will guide decisions about which medications could be helpful and which could be potentially dangerous.
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.