CMT 1X: A novel mutation associated with central conduction slowing on brainstem

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Rinsho Shinkeigaku. 2010 Jun;50(6):399-403

A novel mutation in X-linked Charcot-Marie-tooth (CMTXI) disease associated with

central conduction slowing on brainstem auditory evoked potential (BAEP)

Akimoto C, Morita M, Yamamoto M, Nakano I.

Division of Neurology, Department of Internal Medicine, Jichi Medical

University.

Abstract

CMTX1, the second most common type of inherited hereditary motor and sensory

neuropathy (HMSN), is associated with mutations of the gene for the gap junction

protein connexin 32 (Cx32). In this condition, central conduction velocity is

known to be delayed, presumably because mutated Cx32 is expressed in

oligodendrocytes.

A 45-year-old man presented with a 5-year history of progressive gait

disturbance due to leg muscle weakness. The family history revealed that the

mother had also progressive gait disturbance in her early 40s, and the younger

sister could not walk faster than before at the age of 41.

On neurological assessment, the patient exhibited pes cavus, distal muscle

atrophy and weakness, and absence of the knee and ankle jerks. Touch sensation

was impaired in the both feet. Motor and sensory nerve conduction velocities

were reduced to 30-36 m/s with mild temporal dispersion. Sural nerve biopsy

revealed diffuse loss of large myelinated fibers with the remaining large and

intermediate nerve fibers being frequently surrounded by a thin myelin sheath.

Onion bulb formation was only occasional and mild in degree. His hearing acuity

was normal on pure-tone audiometry, but BAEP test demonstrated prolonged central

conduction time (-I wave 1.8 milliseconds, I-V wave 6.4 milliseconds).

The BAEP findings prompted us to choose Cx32 gene to analyze first to find a

novel mutation of two (A and T) base pairs deletion at codons 277 and 278

(Met93fs). Thus, the present case indicates that Cx32 gene mutation should be

targeted first in case of HMSN with abnormal BAEP.