CMT2I is caused by autosomal dominant mutations in the MPZ gene. Other mutations in this gene are associated with causing several other types of CMT.
CMT2I symptoms usually start to occur after the CMTer is 30 years old, and usually before 50 years old, but some don’t show signs until about 60 years old. CMTers who have CMT2I, are usually clinically normal until symptom onset, and then usually progress rapidly to a painful neuropathy. The lower leg weakness that is often experienced by CMTers who have CMT2I can lead to wheelchair-dependency.
In addition to the classic weakness, atrophy, and sensory loss associated with CMT, CMTers who have this CMT2I causing mutation in the MPZ gene can also experience poorly reactive pupils and can experience significant hearing loss. This is such a distinct occurrence that axonal CMT that is caused by autosomal dominant mutations in the MPZ gene when there is poorly reactive pupils and hearing loss is referred to as CMT2J, and the same but without the pupillary involvement and hearing loss is referred to as CMT2I.