Disease Progression in Charcot-Marie-Tooth Disease Type 4B (CMT4B) Associated With Mutations in Myotubularin-Related Proteins 2 and 13

Alessandro Bertini; Mary M Reilly; Chiara Pisciotta; Stefano C Previtali; Yesim Parman; Esra Battaloglu; Matilde Laurà; Julian Blake; Sabrina Sacconi; Shahram Attarian; Tanya Stojkovic; Mounia Bellatache; Sonia Nouioua; Meriem Tazir; Arman Cakar; Antonio Gambardella; Paola Valentino; Richard A Lewis; Rita Horvath; Alberto A Zambon; Mario Sabatelli; Marco Luigetti; Stefano Tozza; Fiore Manganelli; David N Herrmann; Steven S Scherer; Nicole Kressin; Kailee Ward; Alessandra Bolino; Michael E Shy; Davide Pareyson; CMT4B Study Group

doi:10.1111/ene.70084

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Disease Progression in Charcot-Marie-Tooth Disease Type 4B (CMT4B) Associated With Mutations in Myotubularin-Related Proteins 2 and 13

Journal article

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Disease Progression in Charcot-Marie-Tooth Disease Type 4B (CMT4B) Associated With Mutations in Myotubularin-Related Proteins 2 and 13

Alessandro Bertini, Mary M Reilly, Chiara Pisciotta, Stefano C Previtali, Yesim Parman, Esra Battaloglu, Matilde Laurà, Julian Blake, Sabrina Sacconi, Shahram Attarian, …

European journal of neurology, Vol.32(2), e70084

02/2025

DOI: 10.1111/ene.70084

PMCID: PMC11822262

PMID: 39943887

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Abstract

In 2019, we conducted a cross-sectional study, collecting information on 50 patients with CMT4B, an ultrarare CMT subtype, to better define the clinical phenotype. We now aimed at investigating disease progression in 26 patients with CMT4B1/CMT4B2, recruited from the previous study and among the Inherited Neuropathy Consortium. We retrospectively analysed disease progression in patients with CMT4B1/CMT4B2, collecting MRC scores from nine muscle pairs, Charcot-Marie-Tooth Examination Score (CMTES), and a minimal dataset of clinical information (walking difficulties, aids dependency, upper limb impairment, cranial nerves involvement) at baseline and follow-up visits. Thirteen centres from four continents were involved. Thirteen CMT4B1 and 13 CMT4B2 patients were followed up for 7.1 ± 4.9 and 7.9 ± 4.5 years, respectively. During follow-up, walking aid dependency increased: two CMT4B1 patients adopted AFOs (overall 11/12 at follow-up), and one started using wheelchair (6/12 at follow-up) at the age of 19; among CMT4B2 patients, two more required unilateral support in walking (4/11 at follow-up) by the age of 33 and 49 years, respectively. We found that disease progression, as measured by CMTES, was faster in CMT4B1 as compared to CMT4B2 patients (ΔCMTES/year 0.7 vs. 0.3, p = 0.037) but tended to slow down over time as burden of disease increased. At the end of follow-up, CMT4B1 was associated to higher disability. This international collective effort enabled collection of relevant data for characterizing natural history and estimating disease progression of CMT4B1/CMT4B2 ultrarare diseases, aiming at improving their management and paving the way for designing future clinical trials.

Mutation

Adolescent

Adult

Charcot-Marie-Tooth Disease - genetics

Charcot-Marie-Tooth Disease - physiopathology

Cross-Sectional Studies

Disease Progression

Female

Humans

Male

Middle Aged

Protein Tyrosine Phosphatases, Non-Receptor - genetics

Retrospective Studies

Young Adult

Details

Title: Subtitle: Disease Progression in Charcot-Marie-Tooth Disease Type 4B (CMT4B) Associated With Mutations in Myotubularin-Related Proteins 2 and 13
Creators: Alessandro Bertini - Fondazione IRCCS Istituto Neurologico Carlo Besta
Mary M Reilly - National Hospital for Neurology and Neurosurgery
Chiara Pisciotta - Fondazione IRCCS Istituto Neurologico Carlo Besta
Stefano C Previtali - IRCCS Ospedale San Raffaele
Yesim Parman - Istanbul University
Esra Battaloglu - Boğaziçi University
Matilde Laurà - National Hospital for Neurology and Neurosurgery
Julian Blake - National Hospital for Neurology and Neurosurgery
Sabrina Sacconi - Centre Hospitalier Universitaire de Nice
Shahram Attarian - Aix-Marseille Université
Tanya Stojkovic - Sorbonne Université
Mounia Bellatache - University of Algiers Benyoucef Benkhedda
Sonia Nouioua - University of Algiers Benyoucef Benkhedda
Meriem Tazir - University of Algiers Benyoucef Benkhedda
Arman Cakar - Istanbul University
Antonio Gambardella - Magna Graecia University
Paola Valentino - Magna Graecia University
Richard A Lewis - Cedars-Sinai Medical Center
Rita Horvath - University of Cambridge
Alberto A Zambon - IRCCS Ospedale San Raffaele
Mario Sabatelli - Centro Clinico Nemo
Marco Luigetti - Università Cattolica del Sacro Cuore
Stefano Tozza - University of Naples Federico II
Fiore Manganelli - University of Naples Federico II
David N Herrmann - University of Rochester
Steven S Scherer - University of Pennsylvania
Nicole Kressin - University of Iowa Hospitals and Clinics
Kailee Ward - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Alessandra Bolino - IRCCS Ospedale San Raffaele
Michael E Shy - University of Iowa
Davide Pareyson - Fondazione IRCCS Istituto Neurologico Carlo Besta
CMT4B Study Group
Resource Type: Journal article
Publication Details: European journal of neurology, Vol.32(2), e70084
DOI: 10.1111/ene.70084
PMID: 39943887
PMCID: PMC11822262
NLM abbreviation: Eur J Neurol
ISSN: 1468-1331
eISSN: 1468-1331
Publisher: WILEY
Grant note: Charcot-Marie-Tooth Association Italian Ministry of Health (RRC) U54 NS065712 / NINDS NIH HHS
Language: English
Date published: 02/2025
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984791074002771

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