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Charcot-Marie-Tooth Disease (CMT)


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 The onset of symptoms begins in the second and third decades of life, a bit later than in CMT1. CMT2 usually involves more loss of sensation than CMT1. The ability to walk is often lost by the time a patient reaches their mid-teens.

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
Diagnosis Associated Gene
CMT2B RAB7 9,10
CMT2C TRPV4 11,12
CMT2E NEFL 14,15,16
CMT2I MPZ 18,19,20,21
CMT2K GDAP1 22,23,24
CMT2M DNM2 26,27
CMT2P LRSAM1 28,29
CMT2 (no subtype assigned) MT-ATP6 33


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