This disease is genetic, although often goes undiagnosed. It affects the nerves that transmit information and signals, from the brain and spinal cord, to and from the rest of the body, especially sensory information such as touch. Charcot-Marie-Tooth Disease (CMT) can also directly affect the nerves that control the muscles. It does not, in fact, affect the teeth; rather, it is named after the three physicians who described it in 1886. Diagnosis often occurs as muscle weakness typically becomes more noticeable in the adolescent years or early adulthood, but the onset of the disease can occur at any age.
Longer nerves are affected first, so symptoms typically are noticed first in the feet and lower legs and then affect the fingers, hands, and arms. Most individuals with CMT have some amount of physical disability, although some never know they even have the disease, and others have some characteristics, but not enough to draw attention for diagnosis.
CMT is one of the most common inherited neurological disorders, affecting 2.6 million people worldwide. Nearly all cases are inherited, which is why it is often known as hereditary motor and sensory neuropathy. This is an autosomal dominant and recessive, X-linked gene mutation. Meaning, only one copy of the CMT gene from either parent is needed to get the disease, when dominant and if so, the child has 50 percent chance of inheriting the disease. Recessive disorders occur when a child receives two mutated genes, from both parents, but neither parent would normally have the disease. Their children have a 25 percent chance of inheriting the disease. There are some cases in which a new mutation occurs spontaneously in the person's genetic material during conception without having been passed down through the family.
Unfortunately, one can have to different types of CMT, because multiple genes can have variants and each cause a different form of the disease. There is currently no cure for CMT but it can be managed with supportive therapy. It typically isn't life-threatening, and rarely affects muscles in vital functions like breathing. Most of these individuals have a normal life expectancy.
If you think of your nervous system as an electrical system, then think your nerve cells communicating down long, thin wires called the axons. These axons are surrounded by myelin, which is a covering similar to the insulation on an electrical wire and aids in the speed of that transmission. When these are compromised, either the axon or the myelin sheath, the signals are either slowed or weak. The nerve cells then struggle to communicate to the muscle or to relay sensory information from the legs back to the spinal cord and the brain.
When our genes are compromised, have variants or have what we use to call, mutations, then they may express this condition. Multiple genes can be linked to CMT, more than 40, in fact, and as I mentioned, some individuals have more than one mutation. More than half of cases though, are caused by a duplication of the PMP22 gene on chromosome 17. Although different proteins may be abnormal in the various expressions of CMT, all of these expressions mainly affect the normal function of the peripheral nerves. These seem to affect the coating, which distorts or blocks nerve signals, or the axon itself is impacted.
Over time these nerves can actually degenerate and lose their ability to communicate entirely with the more distant targets, typically the arms, hands, legs, and feet. Motor nerve degeneration results in muscle weakness and decreased muscle bulk in the arms, legs, hands, and feet. Most notice weakness first, or even paralysis of the feet or lower legs. Foot drop may occur or a high-stepped gait with frequent tripping or falling. They may also notice problems with their balance. High arches and curled toes are common (hammertoes). The lower legs sometimes look like an inverted champagne bottle due to the loss of muscle bulk.
As the disease progresses, fine motor skills are lost and sensory perception is lost so that one can't feel heat, cold, or touch. The senses of vibration and position (proprioception) are often decreased as well. Scoliosis is also associated with CMT, as is hip displacement. Many of these individuals develop contractures - chronic shortening of muscles or tendons around their joints, which prevents the joints from moving freely. Muscle cramping is common.
Nerve pain ranges from mild to severe, and some individuals may need to rely on foot or leg braces or other orthopedic devices to maintain mobility. Some experience tremors and vision or hearing loss. In rare cases, breathing difficulties may occur if the diaphragm is affected. Progression of symptoms is quite gradual.
There are a Few Types of Charcot-Marie-Tooth Disease
As mentioned there are more than 40 expressions so think about these being grouped into categories with the first related to abnormalities in the myelin sheath and the second, related to abnormalities in the myelin sheath. Either the wire or the protective covering is affected. Of course, these break down into several subtypes, but I'll let you dig in further if that is of interest to you. Interestingly, this second type sometimes presents in the vocal cords or with breathing problems. It is the less common type.
There is also a third type, also called Dejerine-Sottas disease, a particularly severe demyelinating neuropathy that begins in infancy. These kids have severe muscle atrophy, weakness, delayed motor skills development, and sensory problems. Symptoms may progress to severe disability, loss of sensation, and curvature of the spine. This is rare, and caused by multiple gene mutations, including PMP22, MPZ, and EGR2, and can be inherited either dominantly or recessively.
Another type, the fourth type, also has several subtypes but typically presents with muscle weakness in the legs, during childhood. By adolescents these individuals typically are unable to walk. It is quite rare in the United States.
The X-linked form of CMT, is the second most common expression and is caused by mutations in a gene that provides instructions for making the protein connexin-32 found in myelinating Schwann cells. Males show moderate to severe symptoms in late childhood or adolescence and females tend to have a more mild version, and maybe don't really demonstrate many symptoms.
How do I get Diagnosed?
Visit your primary care provider. We will dig into your history, your family history, and offer a neurological exam. We want to identify muscle weakness in the arms, legs, hands, and feet. We are also looking for decreased muscle mass, reduced tendon reflexes, and sensory loss. We will also look for foot deformities and other feet issues. Mild scoliosis or abnormalities in the hip may alert us. Nerve enlargement is another finding because of thickened myelin sheaths.
If we are suspicious, we'll order a nerve conduction study, an electromyograph (EMG). Electrodes will be placed on the skin, over a muscle or nerve, and these electrodes will offer a small electrical impulse to stimulate the nerves and provide quantifiable information so we can better understand the electrical activity in your muscles and nerves. EMG does involve inserting a needle electrode through the skin to the muscle and measuring the bioelectrical activity of the muscles. We can then see abnormalities in axon loss, distribution and even severity of the peripheral nerve involvement.
As well, genetic testing is helpful. DNA tests aren't available for all types of CMT, but this can be helpful in understanding your specific type. Potentially a nerve biopsy may be ordered. People with the first type of CMT typically show signs of abnormal myelination, and people with the second type often show axon degeneration without evidence of demyelination.
How do we Treat Charcot-Marie-Tooth disease?
There is no cure. Physical and occupational therapy is helpful. Braces and other orthopedic devices may be necessary, or even orthopedic surgery. Pain relief drugs may be prescribed for severe nerve pain. Movement is key. These individuals must maintain mobility, flexibility, and muscle strength. Yes, of course, I am going to suggest, strongly, that these individuals regularly attend yoga. Building stamina is important, as well as increased endurance, and of course, maintaining overall health and wellness.
Braces are often necessary for the ankles, but initially, high top shoes can be helpful in preventing ankle sprains. Thumb splints can help with hand weakness and loss of fine motor skills. Gene therapy is currently being researched, and is promising. Other studies lean into nerve growth factors, such as offering androgen hormones to prevent nerve degeneration.
Of course, my thoughts go to alpha lipoic acid for this condition. ALA is an antioxidant and has mostly been studied in individuals with diabetes, but because they often suffer neurodegenerative disease. There is some evidence that ALA can help reduce pain in those with CMT, but there isn't really any evidence, as I am aware, with whether it does prevent nerve damage in these individuals. It simply hasn't been studied, so that doesn't mean it doesn't work. The mechanisms of nerve injury is different though, between diabetes and CMT. This is inexpensive and helpful in many ways so certainly worth a try, even if only to minimize numbness and pain. Combined with Evening primrose oil, this might even be more advantageous for neuropathy.
L-carnitine is recommended for many who struggle to turn fat into energy with other muscle diseases, so may be advantageous here as well. Our energy centers within each cell, our mitochondria, really enjoy CoEnzymeQ10 so again, this may help with energy. Vitamin C may be helpful, but again, I am leaning into the ALA supplementation and would even encourage administration intravenously. Not expensive and this route would increase absorption, plus it benefits the brain.