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Charcot-Marie-Tooth Disease (CMT)

CMT2

What is Charcot-Marie-Tooth disease type 2 (CMT2)?

CMT type 2 (CMT2) is a subtype of CMT that is similar to CMT1 but is less common. CMT2 is typically inherited in an autosomal dominant pattern but in some cases can be inherited in an autosomal recessive pattern.4,5,6 CMT2 represents 12% to 36% of all CMT cases.7

What are the symptoms of CMT2?

CMT2 is characterized by distal weakness, atrophy, sensory loss, decreased deep-tendon reflexes, and variable foot deformity.8 Onset of symptoms occurs later in CMT2 than CMT1, typically between the ages of 5 and 25 years.9,10 CMT2 is generally less severe than CMT1, with more motor than sensory involvement.10

What causes CMT2?

Unlike CMT1, which results from damage to the myelin sheath insulating axons, CMT2 is caused by direct damage to nerve axons themselves. CMT2 is commonly referred to as “axonal” CMT.

CMT2A is the most common subtype of CMT2 (it accounts for 20% of the cases of axonal CMT) and is caused by defects in the MFN2 gene. The MFN2 gene encodes for mitofusin 2, which is a protein involved in the fusion of cellular mitochondria.

Other rarer forms of CMT2 and their gene defects include:

Diagnosis Associated Gene
CMT2B RAB7 11,12
CMT2C TRPV4 13,14
CMT2D GARS 15
CMT2E NEFL 16,17,18
CMT2F HSPB1 19
CMT2I MPZ 20,21,22,23
CMT2K GDAP1 24,25,26
CMT2L HSPB8 27
CMT2M DNM2 28,29
CMT2P LRSAM1 30,31
CMT2S IGHMBP2 32,33
CMT2T MME 34
CMT2 (no subtype assigned) MT-ATP6 35

References

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  3. Sabet, A. et al. Skin biopsies demonstrate MPZ splicing abnormalities in Charcot-Marie-Tooth neuropathy 1B. Neurology (2006). doi:10.1212/01.wnl.0000238499.37764.b1
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