Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies.  The condition leads to progressive peripheral nerve dysfunction, primarily involving distal limb muscles and resulting in weakness, atrophy, and sensory loss.

The pathogenesis of CMT involves mutations in genes coding for peripheral nerve axonal or myelin proteins.  The genetic mutations disrupt the integrity of myelin (in demyelinating types) or the structure and function of axons (in axonal types), leading to impaired nerve conduction and eventual muscle atrophy and weakness.  CMT is broadly classified into subtypes 1-4 based on genetics and clinical manifestations, with type 1 being the most common.  CMT type 1 is typically a demyelinating disorder.

CMT is one of the most common inherited neurologic disorders.  The most common pathogenic variant (causing CMT type 1) is a duplication of the