Charcot-Marie-Tooth disease: experience from a large Italian tertiary neuromuscular center

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.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    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

    Article  Google Scholar 

  2. 2.

    Pisciotta C, Shy ME (2018) Neuropathy. Handb Clin Neurol 148:653–665

    Article  Google Scholar 

  3. 3.

    Reilly MM, Murphy SM, Laura M (2011) Charcot-Marie-Tooth disease. J Peripher Nerv Syst 16(1):1–14

    Article  Google Scholar 

  4. 4.

    Reilly MM, Shy ME (2009) Diagnosis and new treatments in genetic neuropathies. J Neurol Neurosurg Psychiatry 80(12):1304–1314

    CAS  Article  Google Scholar 

  5. 5.

    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

    CAS  Article  Google Scholar 

  6. 6.

    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

    Article  Google Scholar 

  7. 7.

    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

    CAS  Article  Google Scholar 

  8. 8.

    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

    Article  Google Scholar 

  9. 9.

    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

    CAS  Article  Google Scholar 

  10. 10.

    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

    CAS  Article  Google Scholar 

  11. 11.

    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

    CAS  Article  Google Scholar 

  12. 12.

    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

    Article  Google Scholar 

  13. 13.

    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

    Article  Google Scholar 

  14. 14.

    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

    Article  Google Scholar 

  15. 15.

    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

    CAS  Article  Google Scholar 

  16. 16.

    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

  17. 17.

    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

    CAS  Article  Google Scholar 

  18. 18.

    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

  19. 19.

    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

    CAS  Article  Google Scholar 

  20. 20.

    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

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Massimo Russo.

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

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

Keywords

  • Neuropathy
  • Genetic
  • Charcot-Marie-Tooth
  • Clinical records
  • Novel mutations