In this study, the authors evaluated, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes and rarer forms of CMT caused by mutations in RAB7 and GDAP1 genes. Axonal loss examinations revealed that the density of both Meissner corpuscles and intrapapillary myelinated endings was reduced in skin samples from patients with CMT1A and all the other CMT genotypes. Nodal gaps were larger in all the CMT genotypes though widening was greater in CMT1A. Internodal lengths were shorter in all the CMT genotypes, and patients with CMT1A had the shortest internodes of all the patients. The uniformly shortened internodes in all the CMT genotypes suggested that mutations in both myelin and axon genes may developmentally impede internode formation. The extent of internodal shortening and nodal gap widening are likely both important in determining nerve conduction velocities in CMT. This study extends the information gained from skin biopsies on morphologic abnormalities in various forms of CMT and provides insights into potential pathomechanisms of axonal and demyelinating CMT.
