ĐẶC ĐIỂM BỆNH CHARCOT-MARIE-TOOTH PHÂN NHÓM HUỶ SỢI TRỤC VÀ KHÔNG PHÂN LOẠI ĐƯỢC TẠI VIỆT NAM – MỘT NGHIÊN CỨU QUAN SÁT ĐA TRUNG TÂM

Abstract

Objective: Charcot-Marie-Tooth disease (CMT) includes axonal and unclassified subtypes that that pose considerable genetic diagnostic challenges. With scarce data in Vietnam, we aimed to delineate their clinical, electrophysiological, and genetic features in a Vietnamese cohort. Subject and methods: This case-series was conducted at three tertiary centers – namely, Military Hospital 175, University of Medicine and Pharmacy, and Children Hospital 2 – between March 2023 and December 2024. Patients with clinically diagnosed CMT underwent electrophysiological classification. Genetic testing involved MLPA and multi-gene next-generation sequencing panels. Axonal cases were sub-grouped by MFN2 variant status. Results: Of 43 probands, 39.5% (17/43) had axonal and 14.0% (6/43) unclassified CMT; overall genetic diagnostic yield was 79.1%. Axonal CMT showed male predominance (70.6%), typical onset at 6-15 years, and a 64.7% genetic diagnostic rate. MFN2 variants (4/17 axonal cases) correlated with earlier onset, positive family history (50%), and greater disease severity. Unclassified CMT (n=6) presented with early onset (<5 years in 50%), a severe phenotype (median MRC 54), no family history, and an 83.3% genetic yield from diverse genes (including PMP22, MFN2, GJB1, MPZ). Conclusion: This study reveals distinct profiles for axonal and unclassified CMT. MFN2 variants define a severe, early-onset, often familial subgroup of axonal CMT. Unclassified CMT is also severe, early-onset, and genetically heterogeneous.