Late-onset CMT neuropathy in the NGS era: a 10-year retrospective study.

Authors

Etienne Fortanier, Nathalie Bonello-Palot, Annie Verschueren, Ludivine Kouton, Aude-Marie Grapperon, Emmanuelle Salort-Campana, Giovanni Corazza, Virginie Milhe de Bovis, Luce Barbat du Closel, Emilien Delmont, Shahram Attarian

Published in

Journal of neurology. Volume 273. Issue 10. Sep 26, 2026. Epub Sep 26, 2026.

Abstract

Late-onset Charcot-Marie-Tooth (CMT) disease remains under-recognized and may mimic acquired neuropathies in older adults. We aimed to determine the prevalence and clinical, electrophysiological, and genetic characteristics of genetically confirmed late-onset CMT and to identify features distinguishing it from late-onset non-CMT neuropathies.
We retrospectively reviewed all patients who underwent next-generation sequencing (NGS) for suspected hereditary neuropathy between 2015 and 2025 at a single neuromuscular referral center. Late-onset CMT was defined by symptom onset after 50 years and a class 5 pathogenic variant. Clinical, electrophysiological, genetic, and functional data were collected. Patients were compared with a 2:1 age- and sex-matched control group with late-onset neuropathies, negative CMT-targeted NGS, and a confirmed alternative diagnosis.
Among 642 patients tested after age 50, 57 had genetically confirmed late-onset CMT (8.9%). Pes cavus (80.7%) and a family history of neuropathy (63.2%) were the most frequent clinical features, while disability remained mild. Pathogenic variants involved 20 genes, with a 32% prevalence of PMP22 duplication and frequent involvement of MME, LRSAM1, MPZ, and MFN2. The main alternative diagnoses were inflammatory, idiopathic axonal, and toxic neuropathies. Compared with controls (n = 114), family history, pes cavus, and median nerve conduction velocity < 38 m/s were independently associated with late-onset CMT in multivariate analyses.
Late-onset CMT accounts for a substantial proportion of neuropathies after age 50. Family history, pes cavus, and slowed median nerve conduction should prompt comprehensive genetic testing, particularly including genes associated with late-onset phenotypes.

PMID:
42799779
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

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