CMT2C

CMT2C is caused by autosomal dominant mutations in the TRPV4 gene. CMT2C has wide variability but can be particularly severe.

CMT2C symptom can start to occur in early childhood, and all the way through to late adulthood. CMTers who have CMT2C will usually experience lower leg/ankle/feet weakness and atrophy leading to foot deformities such as pes cavus (high arches) and hammertoes. A CMTer who has CMT2C will usually experience wrist/hand/finger weakness and atrophy leading to contractures (clawed fingers). A CMTer who has CMT2C might also experience arthrogryposis—a condition in which joints can become fixed or locked.

In addition to the classic symptoms of CMT mentioned above, a CMTer who has CMT2C might also experience intercostal muscle weakness and atrophy (the muscles of the rib cage that assist with breathing), severe scoliosis, weakened vocal cords that can become paralyzed, and the shoulder girdle muscles can become significantly weakened. When there is respiratory involvement in CMT2C, it can be quite severe, sometimes requiring a tracheostomy.

Additionally, CMTers who have CMT2C can experience significant sensorineural hearing loss, and conditions known as neurogenic bladder and/or neurogenic bowel (these are conditions in which there is loss of bladder or bowel function because of damage to the autonomic nerves that control them).

Despite these profound severities that can be associated with CMT2C, sensory loss/abnormalities can be comparatively mild.

Other mutations in the TRPV4 gene are associated with causing several other inherited disorders, including a type of inheritable neuropathy called Distal Hereditary Motor Neuropathy Type VIII, or dHMN-VIII (OMIM 606071), but these particular mutations are specific to those conditions and are not associated with causing CMT2C. dHMN-VIII is considered a type of CMT by many, and many CMT clinics treat dHMNers.