What is the pathophysiology of Charcot-Marie-Tooth type X (CMTX)?

Updated: May 22, 2018
  • Author: Timothy C Parsons, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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CMTX is caused by mutations in connexin32/Gap Junction Beta 1 (Cx32 or GJB1), which maps to chromosome Xq13. Connexins assemble to form intercellular gap junctions, which allow the diffusion of ions and small molecules across apposed cell membranes. Connexin 32 is expressed in many tissues, but is localized in the myelin sheath of large diameter fibers near the nodes of Ranvier. [18, 45]

Axonal and demyelinating changes are mixed in CMTX. Men are clinically and electrophysiologically more severely affected than affected women. Interestingly, nerve conduction velocities in affected women can vary markedly within the same limb, in contrast to men whose conduction velocities tend to resemble the diffusely slow velocities seen in CMT1. This may be partly explained by X-inactivation of Schwann cell precursors during development. The mechanisms by which different Cx32 mutations cause CMT1X are not fully understood. Phenotype-genotype correlations in CMT1X will be difficult to establish because of phenotypic variability both within and between kindreds. [46, 47, 48]

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