Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease is a progressive condition, and the subtypes show different disease courses. Symptoms of the condition do not remit, and often worsen over time. There are no effective therapies, other than bracing and orthopaedic corrective surgery, and there is no cure.

CMT1A

CMT1A is the most common form of CMT, and as such has considerable natural history data. One study investigated this condition using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) as a measure of longitudinal data and found that, as a group, people with the disorder progressed at a rate of 0.7 points per year, leading to a difference in impairment over a 2-year period.[42]Shy ME, Chen L, Swan ER, et al. Neuropathy progression in Charcot-Marie-Tooth disease type 1A. Neurology. 2008;70:378-383. http://www.ncbi.nlm.nih.gov/pubmed/18227419?tool=bestpractice.com It also found that individuals with CMT1A without concomitant illnesses, such as diabetes mellitus or a second form of CMT, rarely become wheelchair-dependent, with 95% remaining ambulatory.

Symptoms of CMT1A begin between the first and second decades. Orthotics or ankle-foot orthoses are usually required within two decades of symptom onset, and orthopaedic surgery may be required from the first to the sixth decade. Symptoms progress in a length-dependent manner, so that the feet are affected before the ankles, which are in turn affected before the hands, and there is usually no proximal muscle involvement. Patients are likely to require life-long bracing and may require aids for utility function over time.

CMT2A

CMT2A is usually more severe than CMT1A. Most individuals affected with CMT2A have significant motor weakness in the pre-school and school-age years, and will be non-ambulatory by the age of 20 years.[43]Feely SM, Laura M, Siskind CE, et al. MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology. 2011 May 17;76(20):1690-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100135 http://www.ncbi.nlm.nih.gov/pubmed/21508331?tool=bestpractice.com Sensory impairment is not affected until later in the disease course. Severe muscle atrophy of the distal legs and arms and proximal muscle weakness may occur. Some cases of CMT2A are associated with optic nerve atrophy and/or respiratory insufficiency due to weakness of the diaphragm, and the latter may lead to premature death. Many of the severe forms of CMT follow this disease course.