Electrophysiological findings in SH3TC2 neuropathy mimicking inflammatory neuropathies.

Background: Biallelic SH3TC2 variants lead to autosomal recessive Charcot-Marie-Tooth type 4C (CMT4C) which is typically demyelinating and associated with early-onset spinal deformities. Electrophysiology typically reveals a non-uniform conduction velocity (CV) slowing, a pattern traditionally linked to inflammatory neuropathies, potentially leading to diagnostic misinterpretation.

Objective and methods: Clinical and neurophysiological data from 19 patients belonging to 16 unrelated families with confirmed CMT4C were retrospectively collected across six neuromuscular reference centres in Brazil.

Results: Among the 19 patients, consanguineous parentage was found in 11 patients. Most patients exhibited symptom onset before age 10, and difficulty walking was the most common presenting symptom. A high rate of initial misdiagnosis was noted, with six patients initially diagnosed as inflammatory neuropathy. Proximal muscle weakness since initial assessment, present in 13 patients, and non-uniform CV slowing, present in all patients, contributed to this diagnostic misinterpretation.

Conclusion: This is the largest Brazilian cohort of patients with CMT4C to date. Key findings include frequent non-uniform CV slowing, excessive temporal dispersion and a high rate of misdiagnosis, often as acquired demyelinating neuropathy. Clinicians should be aware of the distinctive neurophysiological pattern of SH3TC2-related neuropathy to avoid misdiagnosis, unnecessary ancillary tests and treatment.