Unrecognized Charcot-Marie-Tooth Disease Unmasked by Chemotherapy-Induced Neurotoxicity.
Fernandes Isabel V IV, Melo Sara S, Sousa Gabriela M GM, Pazos Maria Isabel MI et al.
Chemotherapy-induced peripheral neuropathy (CIPN) is among the most prevalent and clinically significant toxicities from systemic cancer treatments, with taxanes being a leading cause. It is characterised by a length-dependent, predominantly sensory axonal neuropathy that can stabilise or improve after treatment discontinuation. However, the clinical course can be profoundly altered by underlying peripheral nerve pathology. We report the case of a 68-year-old woman with luminal B, HER2-negative breast cancer who developed severe peripheral neuropathy during adjuvant chemotherapy with doxorubicin/cyclophosphamide followed by weekly paclitaxel. Treatment was discontinued after 9 of 12 planned paclitaxel cycles due to grade 3 peripheral neuropathy ( Common Terminology Criteria for Adverse Events (CTCAE) v5.0). Despite cessation of the offending agent and initiation of duloxetine, symptoms continued to worsen, with progressive motor impairment and significant gait instability. Nerve conduction studies revealed a severe sensorimotor demyelinating polyneuropathy, atypical for the predominantly axonal pattern of taxane-induced CIPN. Inflammatory, infectious, paraneoplastic, and metabolic causes were excluded, and empirical corticosteroids and intravenous immunoglobulin proved ineffective. Genetic testing identified a peripheral myelin protein 22 (PMP22) duplication (17p11.2), confirming Charcot-Marie-Tooth disease type 1A (CMT1A), a hereditary demyelinating neuropathy previously subclinical. This case report underscores the value of serial clinical and electrophysiological assessment when neuropathy is atypical, disproportionately severe, or refractory to standard treatment.