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Published on: June 15, 2018
Late-onset CMT neuropathy in the NGS era: a 10-year retrospective study
Etienne Fortanier1,2, Nathalie Bonello-Palot3, Annie Verschueren4
1Reference Center for Neuromuscular Diseases and ALS, European Reference Network Neuromuscular Disorders (ERN-NMD), La Timone University Hospital, Aix-Marseille University, 264 Rue Saint Pierre, 13385, Marseille, France. etienne.fortanier@ap-hm.fr.
Background And Aim:
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.
Methods:
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.
Results:
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.
Discussion:
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.
