Current Issues of the Charcot-Marie-Tooth Disease

Article information

J Korean Med Assoc. 2007;50(5):457-463

Publication date (electronic) : 2007 May 31

doi : https://doi.org/10.5124/jkma.2007.50.5.457

Department of Neurology, Ewha Womans University College of Medicine, Korea. bochoi@ewha.ac.kr

Abstract

Hereditary motor and sensory neuropathy (HMSN), or Charcot-Marie-Tooth (CMT) disease, was described by Charcot and Marie in France and, independently, by Tooth in England in 1886. CMT is the most common form of inherited motor and sensory neuropathy, and is a genetically heterogeneous group of disorders in the peripheral nervous system. Traditionally, CMT has been subclassified into autosomal dominant inherited demyelinating (CMT1) and axonal (CMT2) neuropathies, X-linked neuropathy (CMTX), and autosomal recessive inherited neuropathy (CMT4). There are several related peripheral neuropathies, such as Déjérine-Sottas neuropathy (DSN), congenital hypomyelination neuropathy (CHN), hereditary neuropathy with liability to pressure palsies (HNPP), and giant axonal neuropathy (GAN). A large amount of new information on the genetic causes of CMT has become available, and mutations causing the disease have been associated with more than 20 different genes and 40 chromosomal loci. Advances in our understanding of the molecular basis of CMT have revealed an enormous diversity in genetic mechanisms, despite the clinical entity that is relatively uniform at presentation. Recent studies have shown therapeutic effects of certain chemicals in animal models of CMT1A, which suggests potential therapies for the most common form of CMT, CMT1A. This review focuses on the subgroups of inherited motor and sensory neuropathy on which there has been an explosion of new molecular genetic information over the past decade.

Keywords: Hereditary motor and sensory neuropathy; Charcot-Marie-Tooth disease; Peripheral nervous system; Gene; Mutation

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Figure 1

Portraits of Charcot (A), Marie (B), and Tooth (C). In 1886, Frenchmen Jean Martin Charcot (A; 1825~1893) and Pierre Marie (B; 1853~1940), and Briton Howard Henry Tooth (C; 1856~1925), described hereditary motor and sensory neuropathies for the first time.

Figure 2

Clinical and pathological phenotypes of Charcot-Marie-Tooth disease. Hand muscle atrophy (A) and leg muscle atrophy with high-arched foot deformity (B). Sural nerve teasing studies showed segmental demyelinations (C and D). Electron micrographs showing classic onion bulbs in an unmyelinated axon (E, ×5000), and in a myelinated axon (F, ×14000).