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Lookup NU author(s): Professor Roger Whittaker, Dr Richard Charlton, Dr Rita Barresi, Professor Hanns Lochmuller, Professor Rita HorvathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. Background and purpose: In a subset of patients with inherited peripheral neuropathies the first symptom is atrophy and weakness of the intrinsic muscles of the hands, without involvement of lower limbs until later in the disease course. The exact pathomechanisms of this phenotype are currently unknown. The aim of this study was to characterize the clinical, neurophysiological and genetic features of a group of patients with a clinical diagnosis of upper limb predominant Charcot-Marie-Tooth disease (CMT). Methods: The clinical, electrophysiology and genetic data of 11 patients with upper limb predominant peripheral neuropathy selected from a single-centre cohort of 461 patients diagnosed with inherited neuropathy were analysed and the clinical, electrophysiological and genetic characteristics of these patients reported. Results: An overlapping phenotype of neuropathy and myopathy was detected in two patients. Four patients carry autosomal dominant mutations in GARS and a single patient had a homozygous mutation in SH3TC2. However, the underlying genetic diagnosis could not be confirmed in six patients by gene panel sequencing. Conclusions: Upper limb-onset inherited neuropathies are genetically heterogeneous and, in some cases, there is an overlapping myopathy. Autosomal dominant GARS mutations are the most common genetic cause; however, mutations in other CMT genes may also result in this phenotype in individual patients. The majority of these patients cannot be genetically diagnosed by gene panel testing of known CMT and myopathy genes, suggesting further genetic heterogeneity and highlighting the importance of further genetic investigations in these patients and families.
Author(s): McMacken G, Whittaker RG, Charlton R, Barresi R, Lochmuller H, Horvath R
Publication type: Article
Publication status: Published
Journal: European Journal of Neurology
Year: 2020
Volume: 28
Issue: 1
Pages: 297-304
Print publication date: 01/01/2021
Online publication date: 09/09/2020
Acceptance date: 26/08/2020
Date deposited: 04/06/2021
ISSN (print): 1351-5101
ISSN (electronic): 1468-1331
Publisher: John Wiley & Sons Ltd
URL: https://doi.org/10.1111/ene.14514
DOI: 10.1111/ene.14514
PubMed id: 32909314
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