What is Charcot-Marie-Tooth (CMT) disease?

Updated: Feb 19, 2019
  • Author: Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

The inherited Charcot-Marie-Tooth peripheral neuropathies (CMT) were first described independently by Charcot and Marie in France [1] and by Tooth in England. [2]

The heterogeneous nature and different forms of inheritance of the condition were soon recognized. Dejerine and Sottas described more severe infancy-onset cases, [3]  and Roussy and Levy described cases associated with tremor. [4]

In the late 1960s, neurophysiologic testing allowed the classification of CMT into 2 groups, one with slow nerve conduction velocities and histologic features of a hypertrophic demyelinating neuropathy (hereditary motor and sensory neuropathy type 1 or CMT1) and another with relatively normal velocities and axonal and neuronal degeneration (hereditary motor and sensory neuropathy type 2 or CMT2). [5]

Since the early 1990s, patients with both CMT1 and CMT2, while often clinically similar, were found to be genetically heterogeneous. Now a large and ever increasing number of genetic subtypes has been described, and major advances in molecular and cellular biology have clarified the understanding of the role of different proteins in the physiology of peripheral nerve conduction in health and in disease. Dejerine-Sottas disease is also known as CMT3. Autosomal recessive forms can be also divided into demyelinating (CMT4 or AR-CMT1) and axonal forms (AR-CMT2). Subtypes with velocities within the intermediate range are called DI-CMT. Better understanding of new mutations and the wide range of possible phenotypes led to the development of a new nomenclature proposal, based on the gene and inheritance pattern. However, there is no unanimous agreement, less especially about the nomenclature of the recessive and intermediate-conduction velocity subtypes. 

This article is a brief introduction to the study of CMT and correlates the most common different genotypes and phenotypes. Inherited neuropathies in which autonomic or sensory features predominate, conditions in which the neuropathy is part of a multiple-organ disturbance, and neuropathies with specific metabolic dysfunction are not discussed.


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