Abstract
Introduction
Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disease. Thanks to the advances of the latest generation sequencing, more than 80 causative genes have been reported to date.
Methods
In this retrospective, observational study, we have analyzed clinical, electrophysiological, and genetic data of CMT patients in care at Neuromuscular Center of Messina University Hospital, Messina, Italy, for at least 22 years (from 1994 to 2016). Our center is the only reference center for genetic neuropathies in Sicily and in the southern part of Calabria.
Results
We reviewed the clinical records of 566 patients with the aim to evaluate how many patients received a genetic diagnosis and the distribution of the genetic subtypes. About 352/566 (62.19%) received a genetic diagnosis. The most frequent genetic diagnoses were CMT1A/PMP22 duplication (51.13%), followed by HNPP/PMP22 deletion (15.05%), CMT1B/MPZ mutation (10.22%), CMTX/GJB1 mutation (9.37%), and CMT2F/HSPB1 (4%). Other rare mutations included MFN2 mutation (n. 8 pts), BSCL2 mutation (n.8 pts), PMP22 point mutation (n.7 pts), GDAP1 mutation (n.4 pts), GARSmutation (n. 2 pts), TRPV4 mutation (n. 2 pts), LITAF mutation (n.1 pt), and NEFL mutation (n. 1 pt).
Conclusions
Our study provides further data on frequency of CMT genes, subtypes in a wide Mediterranean area and contributes to help clinicians in addressing the genetic testing workup.
References
Vita G, Vita GL, Stancanelli C, Gentile L, Russo M, Mazzeo A (2019) Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 1: peripheral neuropathies. Neurol Sci 40(4):661–669
Pisciotta C, Shy ME (2018) Neuropathy. Handb Clin Neurol 148:653–665
Reilly MM, Murphy SM, Laura M (2011) Charcot-Marie-Tooth disease. J Peripher Nerv Syst 16(1):1–14
Reilly MM, Shy ME (2009) Diagnosis and new treatments in genetic neuropathies. J Neurol Neurosurg Psychiatry 80(12):1304–1314
Russo M, Laurá M, Polke JM, Davis MB, Blake J, Brandner S et al (2011) Variable phenotypes are associated with PMP22 missense mutations. Neuromuscul Disord 21(2):106–114
Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL et al (2012) Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry 83(7):706–710
Dubourg O, Azzedine H, Verny C, Durosier G, Birouk N, Gouider R, Salih M, Bouhouche A, Thiam A, Grid D, Mayer M, Ruberg M, Tazir M, Brice A, LeGuern E (2006) Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease. NeuroMolecular Med 8(1–2):75–86
Murphy SM, Herrmann DN, McDermott MP, Scherer SS, Shy ME, Reilly MM, Pareyson D (2011) Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. J Peripher Nerv Syst 16(3):191–198
Biasini F, Portaro S, Mazzeo A, Vita G, Fabrizi GM, Taioli F, Toscano A, Rodolico C (2016) TRPV4 related scapuloperoneal spinal muscular atrophy: report of an Italian family and review of the literature. Neuromuscul Disord 26(4–5):312–315
Fridman V, Bundy B, Reilly MM, Pareyson D, Bacon C, Burns J et al (2015) CMT subtypes and disease burden in patients enrolled in the inherited neuropathies consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry 86(8):873–878
Wang R, He J, Li JJ, Ni W, Wu ZY, Chen WJ et al (2015) Clinical and genetic spectra in a series of Chinese patients with Charcot-Marie-Tooth disease. Clin Chim Acta 451(Pt B):263–270
Saporta AS, Sottile SL, Miller LJ, Feely SM, Siskind CE, Shy ME (2011) Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol 69(1):22–33
Gess B, SchirmacherA M, Young P (2013) Charcot-Marie-Tooth disease: frequency of genetic subtypes in a German neuromuscular center population. Neuromuscul Disord. 23(8):647–651
Sivera R, Sevilla T, Vílchez JJ, Martínez-Rubio D, Chumillas MJ, Vázquez JF et al (2013) Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical series. Neurology. 81(18):1617–1625
Manganelli F, Tozza S, Pisciotta C, Bellone E, Iodice R, Nolano M, Geroldi A, Capponi S, Mandich P, Santoro L (2014) Charcot-Marie-Tooth disease: frequency of genetic subtypes in a southern Italy population. J Peripher Nerv Syst 19(4):292–298
Lorefice L, Murru MR, Coghe G, Fenu G, Corongiu D, Frau J et al (2017) Charcot- Marie-Tooth disease: genetic subtypes in the Sardian population. Neurol Sci
Mazzeo A, Muglia M, Rodolico C, Toscano A, Patitucci A, Quattrone A et al (2008) Charcot-Marie-Tooth disease type 1B: marked phenotypic variation of the Ser78Leu mutation in five Italian families. Acta Neurol Scand 118(5):328–332
Mazzeo A, Di Leo R, Toscano A, Muglia M, Patitucci A, Messina C et al (2008) Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation. Eur J Neurol
Stancanelli C, Taioli F, Testi S, Fabrizi GM, Arena MG, Granata F et al (2012) Unusual features of central nervous system involvement in CMTX associated with a novel mutation of GJB1 gene. J Peripher Nerv Syst 17(4):407–411
Stancanelli C, Fabrizi GM, Ferrarini M, Cavallaro T, Taioli F, Di Leo R et al (2015) Charcot-Marie-tooth 2F: phenotypic presentation of the Arg136Leu HSP27 mutation in a multigenerational family. Neurol Sci 36(6):1003–1006
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed Consent
Patients involved in the study provided informed consent.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Gentile, L., Russo, M., Fabrizi, G.M. et al. Charcot-Marie-Tooth disease: experience from a large Italian tertiary neuromuscular center. Neurol Sci 41, 1239–1243 (2020). https://doi.org/10.1007/s10072-019-04219-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-019-04219-1