CLINICAL AND PATHOLOGICAL CORRELATIONS IN CHARCOT-MARIE-TOOTH NEUROPATHY TYPE 1A WITH THE 17P11.2P12 DUPLICATION - A CROSS-SECTIONAL MORPHOMETRIC AND IMMUNOHISTOCHEMICAL STUDY IN 20 CASES

In a cross-sectional, clinical, and morphometric analysis we assessed the correlation between the clinical and pathological evolution of dis ease in 20 unrelated patients of various ages affected by Charcot-Mari e-Tooth neuropathy type 1A (CMT1A) with the 17p11.2p12 (peripheral mye lin protein 22, PMP22) duplication. The severity of neurologic deficit s and slowing of motor conduction velocity at the median nerve did not vary significantly with the patients' age. The amount of demyelinatio n was significantly higher below 15 years than in older age groups; in contrast, myelinated fiber and onion bulb densities were similar at a ll ages. The results indicate that in duplicated CMT1A, the pathologic al process develops early in life and progresses little during the cou rse of the disease. Younger patients had lower g-ratio values, suggest ing that the trigger of demyelination in early years could be a hyperm yelination, resulting from PMP22 overexpression. Yet none of the 20 pa tients examined had immunohistochemical evidence of altered PMP22 expr ession. The early onset and development of the disorder make it diffic ult to detect PMP22 overdosage in nerve biopsies. (C) 1998 John Wiley & Sons, Inc.