Charcot-Marie-Tooth: From Molecules to Therapy

Int J Mol Sci. 2019 Jul 12;20(14):3419. doi: 10.3390/ijms20143419.


Charcot-Marie-Tooth (CMT) is the most prevalent category of inherited neuropathy. The most common inheritance pattern is autosomal dominant, though there also are X-linked and autosomal recessive subtypes. In addition to a variety of inheritance patterns, there are a myriad of genes associated with CMT, reflecting the heterogeneity of this disorder. Next generation sequencing (NGS) has expanded and simplified the diagnostic yield of genes/molecules underlying and/or associated with CMT, which is of paramount importance in providing a substrate for current and future targeted disease-modifying treatment options. Considerable research attention for disease-modifying therapy has been geared towards the most commonly encountered genetic mutations (PMP22, GJB1, MPZ, and MFN2). In this review, we highlight the clinical background, molecular understanding, and therapeutic investigations of these CMT subtypes, while also discussing therapeutic research pertinent to the remaining less common CMT subtypes.

Keywords: Charcot-Marie-Tooth; gene therapy; hereditary neuropathy; molecular therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Charcot-Marie-Tooth Disease / diagnosis
  • Charcot-Marie-Tooth Disease / etiology*
  • Charcot-Marie-Tooth Disease / metabolism
  • Charcot-Marie-Tooth Disease / therapy*
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Genes, Recessive
  • Genes, X-Linked
  • Genetic Association Studies
  • Genetic Therapy
  • Humans
  • Mutation
  • Phenotype
  • Treatment Outcome


  • Biomarkers