There are many different types of Charcot-Marie-Tooth disease (CMT), which are classified according to the gene mutation that causes the disease. The main types (CMT1, CMT2, CMT3, CMT4 and CMTX) and the related subtypes are described in more detail below.
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CMT1
CMT1 is the most common type and is caused by gene mutations the lead to the degeneration of the myelin sheath around the nerve cells. Patients with this type usually notice the first symptoms in adolescence, such as sensory loss, weakness and atrophy of the lower leg muscles.
This type is further divided into several main subtypes:
- CMT1A is inherited in an autosomal dominant pattern and affects chromosome 17 of the gene, which causes changes in the production of the peripheral myelin protein-22 (PMP-22).
- CMT1B follows an autosomal dominant inheritance pattern that affects the production of the myelin protein zero (P0). There are more than 120 gene mutations that have been identified to date that cause this change.
- CMT1C is caused by a mutation in the LITAF gene
- CMT1D is caused by a mutation in the EDFR gene
- CMT1E is caused by a mutation in the NEFL gene
CMT2
CMT2 is caused by gene mutations that lead to defects in the axon of the nerve cells and is less common than CMT 1. It is also typically associated with less severe symptoms.
This type is further divided into several main subtypes:
- CMT2A results from a mutation in Mitofusin 2, which is involved in the process of mitochondrial fusion.
- CMT2B has been linked to the RAB7 gene
- CMT2D is caused by a mutation in the GARS gene
- CMT2E is caused by a mutation in the NEFL gene
- CMT2H is caused by a mutation in the HSP27 gene
- CMT2I is caused by a mutation in the HSP22 gene
CMT3
CMT3, also sometimes referred to as Dejerine-Sottas Disease, is caused by gene mutations that lead to changes in the myelin sheath of the nerve cells. It is a rare type that is caused by a specific point mutation in the P0 or PMP-22 gene.
This type is associated with severe symptoms that initially present in infancy or early childhood, such as severe muscle weakness and sensory difficulties.
CMT4
CMT4 is caused by gene mutations that have not yet been identified but are known to lead to changes in the myelin sheath. This type is also linked to more severe symptoms that present in early childhood. Patients with this type are more likely to eventually lose the ability to walk independently.
This type is further divided into several main subtypes:
- CMT4A is caused by a mutation in the GDAP1 gene
- CMT4B1 is caused by a mutation in the MEMR13 gene
- CMT4B2 is caused by a mutation in the MYMR2 gene
- CMT4C is caused by a mutation in the SH3TC2 gene
- CMT4D is caused by a mutation in the NDG1 gene
- CMT4E is caused by a mutation in the EGR2 gene
- CMT4F is caused by a mutation in the PRX gene
- CMT4H is caused by a mutation in the FDG4 gene
- CMT4J is caused by a mutation in the FIG4 gene
CMTX
CMTX is more common in men than women and is caused by a point gene mutation on the X chromosome, in the connexin-32 gene that is expressed in Schwann cells. These cells form a single segment of the myelin sheath, wrapping around the axons of the nerve cells.
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