Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 76

The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the Connexin 32 gene (Cx32) and is the second most common CMT subtype after CMT1A, in which the 17p11.2 duplication is the underlying molecular defect. CMTX is characterized by no male-to-male transmission, intermediate motor conduction velocities (MCV), and more severe disease in males. In our series of CMT patients, we found 9 different Cx32 mutations in 11 families. Overall there were 26 patients, 13 males and 13 females, aged 11–76 yrs. Age at onset ranged considerably (1–60 yrs), but symptoms began earlier in males (mean 15.4 yrs, 77% within age 20) than in females (mean 25 yrs). All patients were autonomous, but disease severity was greater in males, while 4 female carriers were asymptomatic. Pain and tremor were frequent complaints. Two patients had Babinski sign and one had rest tremor. Nerve conduction studies were performed in 23 patients (13 males, 10 females). Upper limb motor conduction velocities (MCV) ranged between 25 and 57 m/s, and were slower in males (25–48 m/s) than in females (34–57 m/s). MCV were in the upper range of CMT1 (25–38 m/s) in 10/13 males but only in 3/10 females. In some cases, nerve conduction slowing was non-uniform within single nerves, and one female patient had a previous diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. There was considerable asymmetry of involvement between different nerves. The median nerve was often more severely affected than the ulnar nerve, and not only in females, as previously reported, but also in males. Therefore, it appears unlikely that this asymmetry is accounted for by a Lyonization phenomenon. Subclinical abnormalities of central nervous system as revealed by multimodal evoked potential studies were found in 8/10 patients. Expression of Cx32 in the brain is the likely explanation of this finding that confirms previous non-systematic observations. We found seven missense and two nonsense mutations (one novel mutation). Two families presented distinct mutations at the same codon (Arg164), while the Arg22Stop and Arg220Stop mutations were each found in two unrelated cases. Partially supported by a grant from the Italian Ministry of Health to F.T and D.P. (Progetto Ricerca Finalizzata ICS 030.3/RF00.174).