Charcot-Marie-Tooth disease (CMTD) or hereditary motor and sensory neuropathy shows great genetic heterogeneity. The type 1 (CMT-1) or demyelinating form and the type 2 (CMT-2) or neuronal form are two clinically and genetically distinct forms.
Apart from the above mentioned motor and sensory forms, there is another type of neuropathy in which the clinical and neurophysiological involvement is exclusively motor and is known as distal spinal atrophy or hereditary distal motor neuropathy (HDMN), which is a syndrome to be included among the CMTD. The CMT-1 is the most prevalent form and the best understood from the genetic point of view. At least four genes have been reported to be involved: the gene for 22 kDa peripheral myelin protein (PMP-22), situated on the 17p11.2 chromosome (locus CMT-1A); the gene for myelin 0 protein situated on chromosome 1q23 (locus CMT-1B); the gene for conexine 32 (Cx32), found on chromosome Xq13 (locus CMT-X) and the gene EGR2 found on chromosome 10q21.1-q22.1. The genes PMP-22 and PO are related to autosomal dominant forms, the gene Cx32 is transmitted linked to chromosome X and transmission of gene EGR2 has been shown in both autosomal dominant and autosomal recessive forms. In the demyelinating forms with autosomal recessive inheritance, positive linkage has been found on four different loci: 8q21.1 (CMT-4A), 11q23 (CMT-4B), 5q23-33 (CMT-4C) and 8q24 in a form related to deafness (CMT-Lom). Two loci have been identified for the autosomal dominant forms of the HDMN. A large family initially and predominantly of the upper limbs is mapped on chromosome 7p (HDMN-V) and another with the classical phenotype mapped on chromosome 12q24. In the familial neuropathy with liability to pressure palsies in most families, deletion of the locus CMT-1A was found, and in rare cases mutation precisely of the PMP-22 gene. In familial amyotrophic neuralgia, genetic molecular analysis has shown linkage with markers on the chromosome 17q24-25.