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Charcot-Marie-Tooth Disease (CMT)

CMTX

What is Charcot-Marie-Tooth disease type X (X-linked, CMTX)?

CMTX is a subtype of CMT, a genetic, neurological disorder that causes damage to the peripheral nerves — tracts of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs. There are X-linked dominant and X-linked recessive forms of CMT. 6 Together, the X-linked forms account for approximately 10% to 15% of all CMT cases.

What are the symptoms of CMTX?

CMTX has many of the same symptoms of CMT1 and CMT2, including muscle weakness and atrophy, and changes in sensation, mostly in the feet, lower part of the legs, hands and forearms.

Because of its linkage to the X chromosome, CMTX often affects males more severely than females (as females have two X chromosomes and males have only one X chromosome and one Y chromosome). See Signs and Symptoms and Causes/Inheritance for more.

What causes CMTX?

CMTX1 is caused by mutations in the gene for connexin 32 (also known as the GJB1 gene), in the chromosome X, which normally codes for a protein located in myelin, the insulating sheath that surrounds nerve fibers.63 This is the X-linked dominant form of CMT and the second most common form of CMT after CMT1A, accounting for 7% to 12% of all CMT cases.64,6,65 It is the most common X-linked form of CMT, accounting for approximately 50% of X-linked cases.

Other less-common forms of CMTX include:

  • CMTX2, an X-linked recessive form with no identified causative gene66
  • CMTX3, an X-linked recessive form67
  • Cowchock syndrome (also known as CMTX4; CMT with deafness and intellectual disability), caused by an altered AIFM1 gene68
  • CMTX5, an X-linked recessive disorder with deafness and optic neuropathy caused by alterations in the PRPS1 gene. This form has been reported in a Korean family69,70
  • CMTX6, an X-linked dominant disorder described in a family from Australia. The cause is a mutation in the PDK3 gene71

What is the progression of CMTX?

CMTX has its onset in childhood or adolescence, and progression is generally slow. Individuals affected by CMTX1 may loose ambulation function later in life.

What is the status of research on CMT?

CMT research is focused on exploring the effects of defects in genes related to the peripheral nervous system and devising strategies to combat these effects.

References

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