Charcot-Marie-Tooth type 4 C misdiagnosed as CIDP: electrodiagnostic pitfalls and genetic confirmation

Charcot-Marie-Tooth disease type 4 C (CMT4C) is a hereditary neuropathy caused by recessive mutations in the SH3TC2 gene. Due to overlapping symptoms with acquired conditions like chronic inflammatory demyelinating polyneuropathy (CIDP), misdiagnosis is common. This study examines the clinical and electrophysiological profiles of five patients initially misdiagnosed with CIDP but later confirmed to have CMT4C.

Data were collected on demographics, clinical features, nerve conduction studies, and ultrasonographic findings. Patients underwent genetic testing to identify pathogenic SH3TC2 variants.

All patients exhibited early-onset symptoms, including progressive muscle weakness, pes cavus, and spinal deformities; some had a positive family history of neuropathy, while others appeared to be sporadic cases. Nerve conduction studies revealed diminished motor and sensory amplitudes and conduction velocities, with conduction block or temporal dispersion, subsequently reappraised as temporal dispersion-related pseudo-block in the tibial nerves. Genetic testing confirmed SH3TC2 mutations in all cases. Nerve ultrasonography showed an increase in cross-sectional area (CSA), indicating nerve hypertrophy, a characteristic observed in both Charcot-Marie-Tooth disease (CMT) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).

Accurate distinction between CMT4C and CIDP is critical to avoid ineffective treatments. Genetic testing should be considered in refractory or atypical cases of presumed immune-mediated neuropathy. This study highlights that the initial misdiagnosis was driven by electrodiagnostic findings rather than the clinical picture, and identifies specific clues (early onset, parental consanguinity, scoliosis, and poor response to immunotherapy) that should prompt clinicians to pursue genetic testing before attributing NCS findings to an acquired inflammatory process.