A clinical, electrophysiologic, neuropathologic, and genetic study of two large Algerian families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease

Abstract

The hereditary sensory and motor neuropathies form a clinically heterogenous group of disorders, the most frequent of which is Charcot-Marie-Tooth disease (CMT). The autosomal dominant forms of CMT are well characterized, but the nosology of autosomal recessive CMT is still controversial. We report two large consanguineous Algerian families with an autosomal recessive demyelinating CMT and similar clinical manifestations. The clinical, electrophysiologic, and neuropathologic features resemble those of autosomal dominant CMT1, but the early onset and rapid progression of deformities are specific. We excluded by linkage analysis the three loci CMT1A (17p11.2), CMT1B (1q22-23), and CMT4A (8q11-21.1) responsible for demyelinating forms of CMT. These findings suggest a subtype of autosomal recessive neuropathy, the locus of which is undetermined.