A FAMILY STUDY OF CHARCOT-MARIE-TOOTH DISEASE

Cases (47) of Charcot-Marie-Tooth peripheral neuropathy were seen in 18 families within a defined area, with a disease prevalence of 1 in 16,400. Maximum motor nerve conduction velocity (MNCV) measurement divided off 2 types of neuropathy (MNCV < 30 ms-1 and > 40 ms-1), but did not distinguish clinically affected from normal individuals in families whose probands had median nerve MNCV > 40 ms-1. In the neuronal type of neuropathy (MNCV > 40 ms-1) 2 genotypes were seen, autosomal dominant (ADN) and autosomal recessive (ARN). Most cases with the demyelinating type (MNCV < 30 ms-1) had an autosomal dominant genotype (ADD) but 1 family had possible X-linked recessive ineritance (XRD). In 1 autosomal dominant family a father and son had different electrophysiological types of neuropathy. Peroneal muscle weakness was progressive with age in the ADD genotype and certain patterns of phenotypic features were associated with the major genotypes. Age of onset was not found to be reliable in distinguishing genotypes. Care is needed when counseling isolated male cases because of asymptomatic affected females in the autosomal dominant genotypes, and the possibility of ill-defined X-linked forms.