The different classes of this disorder have been divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2). Recent studies, however, show that the pathologies of these two classes are frequently intermingled, due to the dependence and close cellular interaction of Schwann cells and neurons. Schwann cells are responsible for myelin formation, enwrapping neural axons with their plasma membranes in a process called “myelination”.
The molecular structure of the nerve depends upon the interactions between neurons, Schwann cells, and fibroblasts. Schwann cells and neurons, in particular, exchange signals that regulate survival and differentiation during development. These signals are important to CMT disease because a disturbed communication between Schwann cells and neurons, resulting from a genetic defect, is observed in this disorder.
It is clear that interaction with demyelinating Schwann cells causes the expression of abnormal axonal structure and function, but we still do not know how these abnormalities result in CMT. One possibility is that the weakness and sensory loss experienced by patients with CMT is a result of axonal degradation. Another possibility is that axonal dysfunction occurs, not degeneration, and that this dysfunction is induced by demyelinating Schwann cells.
Most patients experience demyelinating neuropathies, and this is characterized by a reduction in nerve conduction velocity (NCV), due to a partial or complete loss of the myelin sheath. Axonopathies, on the other hand, are characterized by a reduced compound muscle action potential (CMAP), while NCV is normal or only slightly reduced.
The disease is named for those who classically described it: Jean-Martin Charcot (1825-1893) and his pupil Pierre Marie (1853-1940) ("Sur une forme particulière d'atrophie musculaire progressive, souvent familiale débutant par les pieds et les jambes et atteignant plus tard les mains", Revue médicale, Paris, 1886; 6: 97-138.), and Howard Henry Tooth (1856-1925) ("The peroneal type of progressive muscular atrophy", dissertation, London, 1886.)
Symptoms and progression of the disease can vary. Breathing can be affected in some; so can hearing, vision, and the neck and shoulder muscles. Scoliosis is common. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can chewing, swallowing, and speaking (as vocal cords atrophy). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as extreme emotional stress.
More details on the types are provided in the table below:
|CMT1A||PMP22||17p11.2||The most common form of the disease, 70-80% of Type 1 patients. Average NCV: 20-25m/s when associated with essential tremor and ataxia, called Roussy-Levy Syndrome|
|CMT1B||MPZ||1q22||Caused by mutations in the gene producing protein zero (P0). 5-10% of Type 1 patients. Average NCV: <15m/s|
|CMT1C||LITAF||16p13.1-p12.3||Causes severe demyelination, which can be detected by measuring nerve conduction velocities. Autosomal dominant. Usually shows up in infancy. Average NCV: 26-42m/s. Identical symptoms to CMT-1A.|
|CMT1D||EGR2||10q21.1-q22.1||Average NCV: 15-20m/s|
|CMT2A||MFN2 or KIF1B||1p36||The cause is likely located on chromosome 1 for the mitofusion 2 protein. Some research has also linked this form of CMT to the protein kinesin 1B. Does not show up on nerve conduction velocity tests, because it is caused by axonopathy.|
|CMT2B||RAB7 (RAB7A, RAB7B)||3q21.|
|CMT2B1||LMNA||1q22||Autosomal recessive axonal CMT, (laminopathy)|
|CMT2C||12q23-q24||May cause vocal cord, diaphragm, and distal weaknesses.|
|CMT2D||GARS||7p15||Patients with mutations in the GARS gene tend to have more severe symptoms in the upper extremities (hands), which is atypical for CMT in general.|
|CMT3||varies||varies||Sometimes called Dejerine-Sottas disease. Rarely found. Autosomal recessive. Average NCV: Normal (50-60m/s)|
|CMT4B2||CMT4B2 (SBF2)||11p15||May be called "SBF2/MTMR13". Autosomal recessive.|
|CMT4C||KIAA1985 (SH3TC2)||5q32||May lead to respiratory compromise.|
|CMT4D||NDRG1||8q24.3||Autosomal recessive, demyelinating, deafness|
|CMT1E||PMP22||17p11.2||Autosomal dominant, demyelinating, deafness|
|CMT4E||EGR2||10q21.1-10q22.1||"CMT4E" is a tentative name|
|CMT4F||PRX||19q13.1-19q13.2||"CMT4F" is a tentative name|
|CMT4J||KIAA0274 (FIG4)||6q21||Autosomal recessive|
|CMTX1||GJB1||Xq13.1||Average NCV: 25-40m/s|
|CMT||with Ptosis and Parkinsonism|
|CMT||type 1 aplasia cutis congenita|
The Charcot-Marie-Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states that "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms.
There are also several corrective surgical procedures that can be done to improve physical condition.
Patent No. 7,552,580 Issued on June 30, Assigned to Wuhan University of Science & Engineering for High Quality Yarn Production Apparatus (Chinese Inventors)
Jul 06, 2009; ALEXANDRIA, Va., July 6 -- Weilin Xu, Zhigang Xia, Wenxiang Ye, Weigang Cui, Wenbin Li and Shangyong Zhang, all from Wuhan,...