Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln mutation.
OBJECTIVE
In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological and histopathological studies have suggested either a demyelinating or an axonal polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve conductions between and within nerves.


METHODS
Two men and one woman have been studied by conduction velocities, sural nerve biopsy with morphometry (one man) and DNA analysis.


RESULTS
In both men motor conduction velocities were slowed in the demyelinating range, conduction velocity differences among nerves in the same subject varied from 13 to 24 m/s, and distal median compound muscle action potential (CMAP) amplitudes were 3-5 times reduced compared to ulnar CMAPs. Abnormal area reduction or excessive temporal dispersion of proximal CMAP was present in at least two nerves in all patients. Sural nerve biopsy showed reduction of large myelinated fibres, cluster formations, occasional onion bulbs. Teased fibres study revealed short internodes for fibre diameter, enlarged Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients.


CONCLUSIONS
In this family conduction slowing and segmental conduction abnormalities, in absence of morphological evidence of de-remyelination, may be related to short internodes, widened Ranvier nodes and the specific effect of the mutation. The occurrence in some CMTX patients of a non uniform involvement between and within nerves, as in acquired demyelinating neuropathies, should be kept in mind to avoid misdiagnoses.
Capasso
M
M
Neurodegenerative Diseases Unit, Institute of Aging, University G. d'Annunzio, Ospedale SS. Annunziata, Via dei Vestini, I-66013 Chieti, Italy.
Di Muzio
A
A
Ferrarini
M
M
De Angelis
M V
MV
Caporale
C M
CM
Lupo
S
S
Cavallaro
T
T
Fabrizi
G M
GM
Uncini
A
A
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009431:Neural Conduction / Q000235:genetics* / Q000502:physiology*; D010543:Peroneal Nerve / Q000503:physiopathology; D013497:Sural Nerve / Q000473:pathology; D013979:Tibial Nerve / Q000503:physiopathology; D014459:Ulnar Nerve / Q000503:physiopathology
D004247:DNA