Genetic testing confirms Charcot-Marie-Tooth type 4C in five patients misdiagnosed with CIDP due to electrodiagnostic pitfalls

Charcot-Marie-Tooth disease type 4C (CMT4C) is a hereditary neuropathy caused by recessive mutations in the SH3TC2 gene, leading to progressive nerve damage. Distinguishing CMT4C from acquired conditions like Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is challenging due to overlapping clinical and electrophysiological symptoms. Misdiagnosis can result in ineffective treatments and prolonged patient suffering. This study addresses the critical need for accurate differentiation to guide appropriate management and avoid unnecessary therapies for presumed immune-mediated neuropathies.

This study retrospectively analyzed the clinical and electrophysiological profiles of five patients who were initially misdiagnosed with CIDP but later confirmed to have CMT4C. Data collected included demographics, detailed clinical features (e.g., muscle weakness, spinal deformities), nerve conduction studies (NCS), and nerve ultrasonographic findings. All patients subsequently underwent genetic testing to identify pathogenic SH3TC2 variants, serving as the definitive diagnostic method to confirm CMT4C and differentiate it from CIDP.

All five patients exhibited early-onset symptoms, including progressive muscle weakness, pes cavus, and spinal deformities like scoliosis; some had a positive family history, while others appeared sporadic. Nerve conduction studies consistently revealed diminished motor and sensory amplitudes and conduction velocities. Crucially, findings initially interpreted as conduction block or temporal dispersion were reappraised as "temporal dispersion-related pseudo-block" in the tibial nerves, a key electrodiagnostic pitfall leading to misdiagnosis. Genetic testing confirmed pathogenic SH3TC2 mutations in all 5 cases, providing the definitive diagnosis. Nerve ultrasonography showed an increase in cross-sectional area (CSA), indicating nerve hypertrophy, a characteristic observed in both CMT and CIDP. This finding alone was insufficient to differentiate the conditions. > The presence of "temporal dispersion-related pseudo-block" in tibial nerves was a critical electrodiagnostic finding that contributed to the initial misdiagnosis of CIDP.