Neuropathies périphériques héréditaires

Abstract

Currently more than 30 genes are known to be responsible for genetically determined neuropathies. Charcot-Marie-Tooth (CMT) disease is the most frequent of these hereditary neuropathies, with a prevalence of 4.7 to 36 per 100 000. In its demyelinating forms (CMT1), approximately 70% of cases are associated with a duplication of the PMP22gene. In its axonal forms (CMT2), 10-20% of the cases may be associated with a mutation of the MFN2gene. For North African patients with recessive transmission, a mutation of the LMNA gene must be sought. It is essential to stress the great variability of the phenotype--clinical, electrophysiological, and histologic--between and within families. A detailed analysis of these criteria, together with consideration of ethnic origin, may guide the search for the causal mutation. Whether the case involves certainly hereditary transmission or a sporadic form, it is desirable to be able to examine the maximum number of the patient's kin, both clinically and electrophysiologically. The forms with recessive transmission usually have a very early onset and are more serious than the dominant forms. The early- and very early-onset forms of CMT are increasingly better distinguished: congenital hypomyelination neuropathy (mutations of PMP22, MPZ or EGR2), or more axonal forms, including SMARD1 (Spinal muscle atrophy with respiratory distress; mutations of IGHMBP2) and EOHMSN (Early-onset hereditary motor and sensory neuropathy; mutations of MFN2). The prevention of cutaneous (ulcerations), bone, and amputation complications is very important in patients with hereditary sensory and autonomic neuropathies, because of the severity of the sensory disorders.