Charcot- Marie-Tooth (CMT):

 

CMT is a neuromuscular disease with a prevalence of about 1 in 2500 (5). CMT causes progressive nerve damage, also known as neuropathy, in both motor and sensory nerves (5). This is a genetically complicated disease, with more than 100 genes related to nerve development and function. There are approximately 6 groups of CMT with multiple subtypes under each category that are differentiated from each other by their genetic cause and often identified by their varying age of onset and neurophysiological symptoms (30).

There is only one group of CMT disease that is classified as an X-linked disorder; CMTX.

  • CMTX accounts for approximately 10-15% of cases of CMT

  • CMTX1, the most common subtype of CMTX, is caused by pathogenic changes in GJB1 on the X chromosome

  • Estimated that ~90% of CMTX cases are caused by changes on GJB1, but in rarer cases, other X chromosome genes are implicated including AIFM1, PRPS1, PDK3, and DRP2 (30).

  • CMTX1 follows an X-linked dominant inheritance pattern

  • CMTX4 and CMTX5 follow an X-linked recessive inheritance pattern

  • The causative gene in the other subtypes of CMTX have not yet been identified (33).

For the remaining groups of CMT disease, each shows a different inheritance pattern, in some cases caused by a single gene change, while in others caused by multiple gene changes. It is also estimated that up to one-third of changes in these genes causing CMT occur de novo (6).

There are further subtypes within each form, but the overarching types include (30):

  • Charcot–Marie–Tooth disease type X (CMTX)

  • Charcot–Marie–Tooth disease type 1 (CMT1)

  • Charcot–Marie–Tooth disease type 2 (CMT2)

  • Charcot–Marie–Tooth disease type 4 (CMT4)

  • Dominant Intermediate CMT (CMTDI)

  • Recessive Intermediate CMT (CMTRI)

Image created by Abbey Sayers

Citations (34, 35)

 

Written by Abigail Sayers; Images by Abigail Sayers unless otherwise noted

Reviewed and Edited by Rachel Baer, MSc, and Andy McCarty, MS, LGC, CGC

Citations

5. Barisic N., Claeys K.G., Sirotković-Skerlev, M., Löfgren, A., Nelis, E., De Jonghe, P. and Timmerman, V. (2008), Charcot-Marie-Tooth Disease: A Clinico-genetic Confrontation. Annals of Human Genetics, 72: 416-441. https://doi.org/10.1111/j.1469-1809.2007.00412.x 

6. Szigeti K., Lupski J. Charcot–Marie–Tooth disease. Eur J Hum Genet 17, 703–710 (2009). https://doi.org/10.1038/ejhg.2009.31

30. Charcot-Marie-Tooth Disease. National Organization for Rare Disorders. (2023, March 22). https://rarediseases.org/rare-diseases/charcot-marie-tooth-disease

33. Nam, S. H. & Choi B. (2019). Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes. Precision and Future Medicine, 3(2), 43-68. https://doi.org/10.23838/pfm.2018.00163. 

34. Charcot-Marie-Tooth disease (CMT): Symptoms & treatment. Cleveland Clinic. (2022, November 29). https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt#management-and-treatment

35. Mayo Foundation for Medical Education and Research. (2023, March 8). Charcot-Marie-Tooth disease. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/charcot-marie-tooth-disease/diagnosis-treatment/drc-20350522#treatment