CHARCOT-MARIE-TOOTH-DISEASE - HISTOPATHOLOGICAL FEATURES OF THE PERIPHERAL MYELIN PROTEIN (PMP22) DUPLICATION (CMT1A) AND CONNEXIN32 MUTATIONS (CMTX1)

The two most common subtypes of Charcot-Marie-Tooth (CMT) disease are CMT1A and CMTX1. To determine whether these different genetic entities display different morphological phenotypes we compared sural nerve bi opsies of CMT1A patients due to PMP22 duplication with biopsies of CMT X1 patients with proven Connexin32 mutations. In CMT1A nerve biopsies we found a severe reduction in myelinated fiber density, hypermyelinat ion as well as demyelination, and a high percentage of onion bulb form ations. CMTX1 nerve biopsies showed significant differences: a higher myelinated fiber density, thinner myelin sheaths, more cluster formati ons, and only few onion bulb formations. Teased fibers studies in CMT1 A patients showed features of demyelination and/or remyelination in al most all fibers. In contrast, teased fibers of CMTX1 patients were uni formly thinly myelinated with 5-10% active axonal degeneration and 15% segmental demyelination. Median nerve motor conduction velocities wer e significantly faster in CMTX1 patients (31.6 +/- 5.5 m/s) than in CM T1A patients (18.2 +/- 6.9 m/s). The possible roles of PMP22 and Conne xin32 in the pathogenesis of CMT are discussed. (C) 1998 John Wiley & Sons, Inc.