Defining Charcot-Marie-Tooth Disease
Charcot-Marie-Tooth Disease (CMT) is also referred to as, 'Hereditary Motor and Sensory Neuropathy,' or, 'Peroneal Muscular Atrophy.' CMT is a group of hereditary conditions. CMT is marked by a slow progression of weakness in the person's muscles, as well as, 'atrophy,' or wasting in their feet, lower legs, forearms and hands. A number of persons with CMT also experience a mild loss of sensation in their toes, limbs and fingers. The weakness the person experiences is due to degeneration of peripheral nerves which connect the person's spinal cord to their muscles, joints and skin. These nerves carry messages in both directions. The weakness the person experiences is not from a degenerative process in the muscle tissue itself.
CMT was named for the three physicians who identified it in the year 1886. CMT is also known as, 'Peroneal Muscular Atrophy,' because it primarily affects the person's peroneal muscles on the shin that allow the person to pull up their foot. Initially, CMT was thought to be a single disorder; it is now thought to be a broad group of disorders which differ in their clinical severity, genetic patterns of inheritance, as well as the sensory neuropathies (HMSN) involved. The term, 'Charcot-Marie-Tooth,' is still used, and usually refers to HMSN Type One.
Symptoms of CMT
Many times the first symptoms of CMT to present itself is difficulty with walking. The cause of this is changes in the shape of the person's feet, such as very flat feet, high arches, or flexed toes; ankle weakness, altered sensation, as well as loss of movement in the ankle and foot. Usually, the person finds that they have to raise their knee higher in order to lift their foot off of the ground. Some persons with CMT have trouble maintaining their balance while standing. Symptoms which are typical of CMT involving the person's upper limbs include difficulty with picking up items, as well as dropping things due to weakness in their fingers, hands, or wrists. A number of persons with CMT experience fatigue.
Types of HMSN
The most common types of HMSN, Types One and Two, are different mainly in the manner in which the function of the peripheral nerves are altered.
HMSN Type One: HMSN Type One involves enlargement of the hypertrophic nerves as well as degeneration of the sheath of fatty material called, 'Myelin,' which insulates a number of the body's nerve fibers. HMSN Type One is also referred to as, 'Hypertrophic Type.' Degeneration of the insulating material presents very slow conduction impulses in the person's nerves.
HMSN Type Two: HMSN Type Two is also referred to as, 'Neuronal Form,' and affects the person's muscles in their lower limbs more than the smaller muscles in their hands which are predominantly affected in Type One. Persons with this type experience a comparatively greater loss of muscle bulk below the knee, as well as weakness in their ankles and feet. The person's nerve fibers called, 'Axons,' instead of the Myelin Sheath, are affected in this type of the disorder. The person's nerve signals in Type Two are conducted more rapidly than in persons with Type One, yet are many times delivered incorrectly to their targets.
There is a very slow progression of the disease in most types of HMSN, as well as an average life expectancy. The rate of progression and severity of the symptoms people experience can vary widely from person to person.
Progression of CMT
As CMT advances muscles in the person's lower legs, and sometimes in the lower third of their thighs, become smaller in size and weaker. The decrease in size and strength of these muscles may affect the person's balance or ability to bend over. The person may develop clawed or hammer toes as well.
Weakness with tremors can be experienced in the person's forearms and hands, commonly in the later stages. The person's intrinsic muscles in their hands may atrophy, causing their fingers to claw. Wrist drop is something else that the person may experience.
Fine motor skills can become more difficult; numbness can become an issue in the person's feet and hands, resulting in a greater risk of self-injury without intention. The person may experience painful sensations on the soles of their feet or in their palms. Pain in the Sciatic nerve is common.
Some persons with CMT can experience respiratory difficulties due to weakness in the muscles of their diaphragm. Dizziness, shortness of breath, fatigue, morning headaches and pain the rib area can result. There is a great deal of variation among persons with CMT and the kinds of symptoms they experience, as mentioned; even among members in the same family.
Age of Onset
Due to the slow progression of CMT, the onset of the disorder is many times difficult to determine. In general, persons affected experience some changes in foot shape in late childhood or early adolescence when affected with HMSN Type One. Persons with HMSN Type Two commonly present symptoms later, usually in early adulthood or middle age.
A diagnosis of CMT is commonly made following a detailed personal and family history and physical examination, including tests of the person's muscle function and their sensory responses. A laboratory test referred to as a, 'Nerve Conduction Velocity/Electromyogram,' may be performed; it measures the speed that impulses are carried down the person's peripheral nerves, as well as the electrical activity of their muscle cells. The person's complete family history is taken, and if possible a careful physical examination of the person's close relatives is performed as well. The goal is to determine if the person's disorder is inherited.
Depending on the person involved, a muscle or nerve biopsy may be performed with the intention of enabling the person's physician to confirm the diagnosis and specify the type, particularly when the person's symptoms are either very severe or mild, and the person's family history of the disorder is not readily apparent. The Electro-physiological nerve conduction velocity studies, as well as the muscle biopsy assist in distinguishing between the different types of HMSN.
Through studying the person's DNA which has been isolated from a blood sample, a diagnosis can be made. Science has discovered that about fifty-percent of persons with HMSN Type One have an extra copy of genetic material within the CMT One Gene. If the duplication is indeed present, it confirms the diagnosis of CMT Type One. The absence of the duplication does not rule out CMT Type One, or another form of HMSN. Should this duplication be found in one person, their family members may be similarly diagnosed through a blood test. There is another gene on chromosome one that has been shown to have changes in it which appear to be causative of CMT Type 1B. As additional genes are isolated which are causing various HMSN subtypes, the role of DNA testing in diagnosing HMSN will expand.
Currently there is no cure for CMT. Changes in foot shape persons with CMT experience, in high arches in particular, may be managed through carefully-fitted shoes and appropriate foot care. Along with good shoes, Ankle-foot orthoses or arch supports within the person's shoes can be useful. Plastic splints can be used in order to prevent further foot drop. In some cases surgical intervention may be helpful. Surgery can help to reduce the person's arch, curling of their toes, or to fuse together some of the bones in their foot. Tendon transfer involves a surgery to prevent changes in a person's foot shape and the need for bone surgery.
Moderate exercise can help persons with CMT to both build muscles and increase the mobility in their joints. Pursuit of active exercise and maintenance of a fitness regime can help to sustain mobility in persons with CMT. When numbness in a person's feet becomes an issue, consistent washing, drying and inspection of the feet for ulcerations is an important thing to pursue. It is important for the person to check their shoes for irritants like small stones or uneven edges in order to maintain skin health.
Some persons with CMT might find that using mobility aids such as walkers, scooters or wheelchairs can be indicated. It is important to first determine which mobility aid is best for the person, and then ensure that any seating involved is both comfortable and correct.
Persons who experience symptoms involving their hands may receive assistance from an Occupational Therapist, who can prescribe aides which can help them to overcome obstacles. Computers, fat pens, lightweight utensils and clothing that is easy to put on are some examples of aides. Regular visits to a doctor may help persons with CMT to express any concerns they may have, as well as to receive treatment for them.
Advances in Molecular Genetics have both extended knowledge concerning CMT and permitted major advances in the understanding of HMSN. Researchers have discovered a variety of genes which, when altered, may cause these disorders. Examples of these genes include the PMP22 gene found on chromosome 17, and the Po gene found on chromosome 1. Both of these genes affect the Myelin Sheath, which covers nerve fibers, providing insulation for the nerves. Scientists are developing a larger understanding of how the Myelin Sheath works.
Alterations in a person's genes which produce proteins vital to the makeup of myelin may prevent it from doing what it is supposed to in a variety of ways. Various changes to these same two genes are believed to be responsible for HMSN Type Three. Scientists are continuing to explore areas of nerve development and function, particularly in relation to the Myelin Sheath, in order to gain additional information about the pathological process in HMSN.
Recent discoveries have led other researchers to look at development of new treatment protocols. Their focus is on the development of a medication that could positively affect an individual's loss of function in the Myelin Sheath related to genetic alterations.