The genetic convergence of Charcot-Marie-Tooth disease types 1 and 2 and the role of genetics in sporadic neuropathy

Abstract

Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically heterogeneous group of inherited neuropathies caused by aberration of the intimate relationship between the myelin sheath and the axon; disorders causing demyelination are classified as CMT1 and those causing axonal loss as CMT2. The mechanisms by which mutations disturb the relationship of the myelin sheath and axon are not fully understood; however, we hypothesize that some mutations affect this relationship more profoundly than others, and thus account for the paradox that mutation of a "myelin gene" can present with electrophysiologic features of CMT2 and vice versa. Also, contrary to popular understanding, inherited neuropathies account for a substantial number of chronic peripheral neuropathies. Because of this observation, we propose that molecular diagnosis is a necessary adjunct for differentiating genetic and acquired peripheral neuropathies, even in sporadic chronic neuropathy.