Phenotypic Spectrum of Myelin Protein Zero-related Neuropathies: a Large Cohort Study from Five Mutation Clusters Across Italy

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2024 Jun 5

PMID 38839277

Authors

Alessandro Bertini

Luca Gentile

Tiziana Cavallaro

Stefano Tozza

Paola Saveri

Massimo Russo

Sara Massucco

Yuri Matteo Falzone

Emilia Bellone

Federica Taioli

Alessandro Geroldi

Giuseppe Occhipinti

Moreno Ferrarini

Eleonora Cavalca

Luca Crivellari

Paola Mandich

Francesca Balistreri

Stefania Magri

Franco Taroni

Stefano Carlo Previtali

Angelo Schenone

Marina Grandis

Fiore Manganelli

Gian Maria Fabrizi

Anna Mazzeo

Davide Pareyson

Chiara Pisciotta

Affiliations

Soon will be listed here.

Abstract

Background: We aimed to investigate the clinical features of a large cohort of patients with myelin protein zero ()-related neuropathy, focusing on the five main mutation clusters across Italy.

Methods: We retrospectively gathered a minimal data set of clinical information in a series of patients with these frequent mutations recruited among Italian Charcot-Marie-Tooth (CMT) registry centres, including disease onset/severity (CMTES-CMT Examination Score), motor/sensory symptoms and use of orthotics/aids.

Results: We collected data from 186 patients: 60 had the p.Ser78Leu variant ('classical' CMT1B; from Eastern Sicily), 42 the p.Pro70Ser (CMT2I; mainly from Lombardy), 38 the p.Thr124Met (CMT2J; from Veneto), 25 the p.Ser44Phe (CMT2I; from Sardinia) and 21 the p.Asp104ThrfsX13 (mild CMT1B; from Apulia) mutation. Disease severity (CMTES) was higher (p<0.001) in late-onset axonal forms (p.Thr124Met=9.2±6.6; p.Ser44Phe=7.8±5.7; p.Pro70Ser=7.6±4.8) compared with p.Ser78Leu (6.1±3.5) patients. Disease progression (ΔCMTES/year) was faster in the p.Pro70Ser cohort (0.8±1.0), followed by p.Ser44Phe (0.7±0.4), p.Thr124Met (0.4±0.5) and p.Ser78Leu (0.2±0.4) patients. Disease severity (CMTES=1.2±1.5), progression (ΔCMTES/year=0.1±0.4) and motor involvement were almost negligible in p.Asp104ThrfsX13 patients, who, however, frequently (78%, p<0.001) complained of neuropathic pain. In the other four clusters, walking difficulties were reported by 69-85% of patients, while orthotic and walking aids use ranged between 40-62% and 16-28%, respectively.

Conclusions: This is the largest (and late-onset CMT2) cohort ever collected, reporting clinical features and disease progression of 186 patients from five different clusters across Italy. Our findings corroborate the importance of differentiating between 'classical' childhood-onset demyelinating, late-onset axonal and mild -related neuropathy, characterised by different pathomechanisms, in view of different therapeutic targets.

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