Kolb et al. (2010) reported 2 sisters with adult-onset distal hereditary motor neuropathy. The proband was a 58-year-old woman who presented with a history of slowly progressive distal arm and leg weakness. Her symptoms began in her early ... Kolb et al. (2010) reported 2 sisters with adult-onset distal hereditary motor neuropathy. The proband was a 58-year-old woman who presented with a history of slowly progressive distal arm and leg weakness. Her symptoms began in her early twenties, when she noticed easy fatigability in her legs, frequent ankle turning, and instability going up and down stairs. The disorder was restricted to the legs until 5 years before presentation, when she noticed bilateral hand weakness. Prior electrophysiologic studies had indicated an axonal neuropathy. Physical examination showed atrophy of the intrinsic foot and hand muscles without pes cavus or toe deformities, distal upper and lower limb weakness with atrophy, steppage gait, and inability to walk on the heels or toes. Sensory examination showed mild loss of light touch over the toes, but otherwise normal sensation. Distal hypo- and areflexia were present. EMG showed signs of chronic denervation in distal lower limb and hand muscles. Her 51-year-old sister was similarly affected, and her mother was reported to be similarly affected.
By candidate gene analysis of 2 sisters with adult-onset distal hereditary motor neuropathy, Kolb et al. (2010) identified a heterozygous mutation in the HSPB3 gene (R7S; 604624.0001). The authors noted that mutations in the heat-shock proteins HSPB1 (602195) ... By candidate gene analysis of 2 sisters with adult-onset distal hereditary motor neuropathy, Kolb et al. (2010) identified a heterozygous mutation in the HSPB3 gene (R7S; 604624.0001). The authors noted that mutations in the heat-shock proteins HSPB1 (602195) and HSPB8 (608014) both result in distal HMN with minimal sensory involvement (HMN2B, 608634 and HMN2A, 158590, respectively).