Abstract

BACKGROUND--The most common form of CMT with slow nerve conduction velocities (CMT type I) is CMT1A, caused by a submicroscopic duplication of a region of DNA on chromosome 17 including the PMP22 gene. This gene is expressed in peripheral nerve but not in the CNS. The second most common form is CMTX, caused by mutations in the connexin32 gene in the X chromosome. Connexin32 is expressed both in brain and in peripheral nerve. These molecular variants are difficult to distinguish clinically. METHODS--Brain stem auditory evoked responses (BAERs) were measured in patients with CTMX and CMT1A. RESULTS--BAERs showed central conduction slowing in male patients with CMTX which did not overlap the normal range. Patients with CMT1A had a delay in wave I latency but otherwise normal responses. These results are consistent with the pattern of expression of PMP22 in the peripheral portion of the eighth nerve (myelinated by Schwann cells) and of connexin32 in the central portion in the brainstem auditory pathways (myelinated by oligodendrocytes). This is the first evidence for central involvement in CMTX. CONCLUSION--BAERs are useful to distinguish CMTX from CMT1A and may assist selection of appropriate patients for connexin32 mutation analysis.