What is Charcot-Marie-Tooth (CMT) disease?
(shar-ko¯’ mä-re´ tooth)
CMT is the acronym for Charcot-Marie-Tooth disease, named after the three physicians who first described it: Drs. Jean-Martin Charcot and Pierre Marie (both from France) and Howard Henry Tooth (of the United Kingdom). It is estimated that CMT affects 3+ million people worldwide, regardless of gender, race, or ethnicity.
CMT is a group of like diseases caused by inherited genetic mutations. CMT damages the peripheral nerves outside of the brain and spinal cord.What is the Peripheral Nervous System?
The nervous system consists of the central nervous system and the peripheral nervous system. The central nervous system consists of the brain and spinal cord. The peripheral nervous system consists of all of the nerves that branch off the central nervous system and extend to the feet and hands. CMT is called a neuromuscular condition because it is the failure of the nerves that cause the malfunctioning of the muscles (unlike muscular dystrophy which affects the muscles themselves).
Peripheral nerves that control muscle movement are often described as being like electrical wires. Each nerve contains bundles of nerve fibers, with an inner core (the axon) that passes signals to muscles causing them to move. The axon is wrapped in insulation. When the myelin is damaged (CMT Type 1 and Type 4), the nerve impulses are conducted more slowly than normal. If the axon itself is damaged (CMT Type 2), the speed of nerve conduction is almost normal, but the strength of the signal is reduced. Both result in impaired electrical messaging to the muscles and therefore malfunctioning of the muscles (weakness and eventual wasting away).
Is CMT progressive?
Yes, all types of CMT are progressive, meaning the symptoms worsen over time.
Is CMT Inherited?
Yes, CMT can be passed on from one generation to the next. It can also occur as a new or spontaneous mutation.
How many genetic mutations are there?
Scientists have identified over 100 different gene mutations causing CMT. Most people (90%) have one of four types of CMT: CMT 1A (PMP 22); CMT 1B (MPZ); CMT 2A (MFN2) and CMT 1X (GJB1).
First signs may include toe-walking, frequent tripping, ankle sprains, clumsiness, and “burning” or pins-and-needles sensations in the feet and/or hands.
Structural foot deformities such as high arches and hammertoes (curled toes) are common, but some people have flat feet and straight toes. Later in the disease process, contractures may develop in the fingers and hands.
Foot drop (inability to lift foot at ankle), poor balance, and problems walking may develop as muscles atrophy in the feet and legs, and some people may have hip dysplasia.
Difficulty with tasks involving manual dexterity, such as writing, grasping or picking up small object or manipulating zippers and buttons can develop as atrophy in the hands sets in and progresses.
Abnormal sensation, loss of ability to feel light touch, the overall sense of touch, and the ability to perceive temperature change can become diminished, or even lost, in CMT. The loss of the ability to sense where one’s body is in space(proprioception) is also common, and many people experience musculoskeletal or neuropathic pain.
Poor tolerance for cool, cold and/or hot temperatures is typical. Many people have chronically cold hands and feet. Additional symptoms may include flexed fingers, contractures, tremor, knee and/or hip problems, muscle cramps, muscle spasms, thenar muscle atrophy (loss of muscle mass between the thumb and forefinger), loss of overall hand strength, absent or reduced reflexes, chronic fatigue, obstructive sleep apnea, poor circulation, scoliosis, kyphosis, hip dysplasia.
Rare symptoms include breathing difficulties caused by respiratory muscle weakness, swallowing or speaking difficulties, neurogenic bladder, hearing loss, optic neuropathy and vocal cord paralysis.
The psychological impact of having CMT can’t be ignored, leading to irritability, depression, anxiety, feelings of hopelessness and guilt.
If you are having suicidal thoughts, immediately call your local suicide hotline or the National Suicide Prevention Lifeline: 1-800-273-TALK (1-800-273-8255), or seek help right away at a local emergency room.
Although there is no drug treatment for CMT, physical/occupational therapy and moderate activity (but not overexertion) can help maintain muscle strength, endurance and flexibility.
AFOs (ankle-foot orthoses) or braces and custom-made shoes can improve gait and balance. When medically indicated, orthopedic surgery can correct deformity and help maintain mobility and function. Occupational therapy and adaptive devices can help people perform activities of daily living. Maintaining a healthy weight and diet is essential for optimal performance.
It is important for people with CMT to maintain what movement, muscle strength and flexibility they have. Strengthening muscles affected by CMT can be challenging, so the best programs work on strengthening unaffected muscles that can help do the work of those that have atrophied because of CMT. Hence, physical therapy and moderate activity are recommended. Overexertion, however, should be avoided. A physical therapist can design an exercise program that fits a patient’s personal strengths and flexibility.
Learn how to manage CMT and find help and additional resources
Exercises that do not put undue stress on the joints are strongly recommended:
- Walking with balance walking poles – click here to learn how to this is beneficial for CMT.
- Exercises you can do at home – click here to watch exercise videos with Rebekah Lee, a physiotherapist living with CMT.
- Tai chi
Learn more about healthy living through THE CMTA exercise series
YES! Some medications are potentially toxic to people with CMT.
The Charcot-Marie-Tooth Association maintains a list of medications that scientists have identified as having a neurotoxic risk for people with peripheral neuropathy. Neurotoxicity occurs when a medication worsens CMT symptoms.
The US FDA has added a warning to the cancer drug, Vincristine HCL, warning against the drug’s use in demyelinating CMT. Vincristine HCL can cause a permanent severe worsening of symptoms in demyelinating types of CMT. Because of this, the US FDA has issued a warning against its use in demyelinating CMT. Scientists have found that the Taxol class of cancer drugs (Taxol, Onxal, Paclitaxel, Docetaxel, Cabazitaxel, and others) pose a significant high neurotoxic risk, but Vincristine HCL is the only drug known to carry a do-not-use warning for CMT.
The CMTA maintains and offers the Neurotoxic Medication List for informational purposes only. All medication decisions must be between you and your physician.
We invite you to visit our medication FAQ page where members of our medical and scientific advisors have answered many questions pertaining to medications. We also invite you to email any questions you have to email@example.com.
CMT that directly damages the peripheral nerve myelin is known as demyelinating CMT (Types 1, 4 and X). When CMT damages the myelin of the peripheral nerves, the nerve can no longer transmit signals efficiently. This damage causes the speeds at which the nerve transmits its signals to become slowed. Over time, the damage to the myelin causes damage to the nerve axon. Although the axon can become damaged over time, this is still a demyelinating CMT.
CMT that directly damages the peripheral nerve axon is known as axonal CMT (Type 2). When CMT directly damages the peripheral nerve axon, the speed at which the nerve transmits a signal remains near normal, but the overall strength of the signal becomes impaired. This impairment of signal strength can be more severe at the points farthest from the spinal cord (distal) than at points closest to the spinal cord (proximal). Because of this difference, axonal CMT is sometimes known as length dependent axonal CMT.
Intermediate CMT refers to a type of CMT that exhibits peripheral nerve conduction characteristics that overlap that which is characteristic of demyelinating CMT and that which is characteristic of axonal CMT. Intermediate is the name given to this type of CMT because, by nerve conduction characteristics, it is neither demyelinating nor axonal – it is somewhere in between – it is intermediate.
Learn more about how the CMT is accelerating research for Demyelinating and Axonal forms of CMT
$17 million since 2008, with another $10 million needed to bring CMT drugs to market
Partnered with more than 32 of the top pharmaceutical, biotech and service companies
NUMBER OF PROJECTS
Over 50 active research projects with the world’s leading research labs
The CMTA is aggressively pursuing treatments and a cure for all types of CMT. Since launching the Strategy to Accelerate Research (STAR) in 2008, the CMTA has been working with preeminent researchers, clinicians, patients and institutions in the global inherited neuropathy community to capitalize on breakthroughs in genetics.
Unlike other neuromuscular diseases, the genetic causes of CMT are known. In fact, more than 90 specific genes that cause the disease have been identified. More importantly, the fact that most of these genetic mutations can be replicated in laboratory models and grown as tissue cultures has opened an extraordinary window of opportunity to develop treatments and cures using the latest pharmaceutical, biotech, and gene therapy technologies.
“STAR is the most important initiative ever undertaken by the Charcot-Marie-Tooth Association,” according to Michael E. Shy, MD, Co-Chair of the Clinical Expert Board. “In addition to developing specific therapies for CMT patients, the translational science employed in the research could have major implications for the treatment of a host of related genetic disorders.”
The CMTA has made unprecedented progress toward therapies for virtually almost all types of CMT. Since the inception of STAR, the CMTA has financed more than 100 projects and committed over $17 million in research. Thanks to support from our donors, STAR continues to gain momentum and the promise of breakthroughs is imminent.