Charcot-Maire-Tooth Disease

Nature of the Genetic Difficulty

Charcot-Marie-Tooth Disease is a group of neurological diseases meaning that the different types affect different genes. Type 1 and most cases of Type 2 are inherited in an autosomal dominant pattern. A single copy of the altered gene can cause the disorder. Most people affected have at least one parent who also has the disease. These diseases are the most common of all neurological diseases and are caused by mutations in up to 14 different genes.
Type 1 is caused by mutations in the following genes: PMP22 MPZ, LITAF, EGR2, and NEFL. Type 2 Charcot-Marie-Tooth disease results from alterations in the following genes: MFN2, RAB7A, LMNA, BSCL2 and GARS, NEFL, HSPB1, MPZ, GDAP1, and HSPB8. Certain DNM2 gene mutations also cause a form of type 2 Charcot-Marie-Tooth disease. Type 4 Charcot-Marie Tooth disease is caused by mutations in the following genes: GDAP1, MTMR2, SBF2, SH3TC2, NDRG1, EGR2, PRX, FGD4, and FIG4. Intermediate forms of the disorder are caused by an altered DNM2 or YARS gene. Type X Charcot-Marie-Tooth disease is caused by mutations in the GJB1 and PRPS1 genes. Mutations in additional genes that have not been identified also cause Type X (subtypes X2, X3, and X4) and intermediate forms of Charcot-Marie-Tooth disease.

Basis Facts of Disease

Charcot-Marie-Tooth Disease is a group of nervous disorders that affect the peripheral nervous system. They cause loss of movement and sensation in the limbs. The first signs usually occur in adolescence or early adulthood although in some cases are seen in childhood. The earliest symptoms involve muscle weakness in the feet, which can cause foot abnormalities such as high arches or curled toes . It may become difficult to flex the foot or to walk on the heel of the foot. These difficulties may cause a higher than normal step and can increase the chance of ankle injuries and tripping. As the disease progress, affected individuals have weakness in their legs and arms. Sensations such as pain, heat, coldness and other feeling.


Onset of symptoms of Charcot-Marie-Tooth Disease is most often in adolescence or early adulthood, however presentation may be delayed until mid-adulthood. Progression of symptoms is very gradual. The degeneration of motor nerves results in muscle weakness and atrophy in the extremities (arms, legs, hands, or feet), and the degeneration of sensory nerves results in a reduced ability to feel heat, cold, and pain. There are many forms of Charcot-Marie-Tooth Disease disease. The severity of symptoms is quite variable in different patients and some people may never realize they have the disorder. Charcot-Marie-Tooth Disease is not fatal and people with most forms of Charcot-Marie-Tooth Disease have a normal life expectancy.

Sources Cited

Charcot-Marie-Tooth Disease CMT Disease- PubMed Health
Retrieved from ""