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Unexpected Intermediate Nerve Conduction Velocity Findings in Charcot-Marie-Tooth Syndromes Classified as Demyelinated or Axonal in a Pediatric PopulationFunding None.
Introduction Among the hereditary motor and sensory neuropathies (HMSN), demyelinating forms are the best characterized, with a clear predominance of CMT1A. The axonal and intermediate forms are less described. The aim of this study is to report the genetic diagnosis of Charcot-Marie-Tooth (CMT) according to the nerve conduction velocity (NCV) findings in a pediatric population.
Methods We retrospectively described a population of HMSN children with a confirmed genetic diagnosis of demyelinated, intermediate, or axonal forms. We compared the results of the genetic analyses with those of motor NCV in median nerve according to whether they were below 25 m/s (demyelinating group); between 25 and 45 m/s (intermediate group), or above 45 m/s (axonal group).
Results Among the 143 children with an HMSN, 107 had a genetic diagnosis of which 61 had an electromyogram. On NCV findings: seven (11%) pertain to the axonal group, 20 (32%) to the intermediate group, and 34 (55%) to the demyelinating group. When NCV was above 45 m/s, CMT2A was the predominant genetic diagnosis (70%) when NCV were below 25 m/s, CMT1A was the predominant genetic diagnosis (71%). Intermediate NCV findings group was the more heterogeneous with seven genetic CMT subgroups (60% CMT1A, CMT1B, CMT1X, CMT2A, CMT2N, CMT4G).
Conclusion Taking NCV values between 25 and 45 m/s to define an intermediate group of CMT in children leads to the inclusion of non-typically “intermediate”, especially CMT1A. We emphasize the broad spectrum of NCV in CMT1A that justified the systematic search of PMP22 duplication/deletion screening before next generation sequencing panel.
KeywordsCharcot-Marie Tooth - hereditary motor and sensory neuropathies - intermediate CMT - axonal CMT - children
Ethical Publication Statement
We declare that we have read the journal's position relating to ethical publication issues and confirm that this report is consistent with those guidelines.
E.B. wrote the first draft of the manuscript, tables, and figure. C.C., U.W.L., and F.R. followed patients included in this study. They all made critical amendments and essential feedback to this manuscript. C.M. and P.L. performed genetic analysis. R.J.-m. and P.C. performed and discussed electroneuromyographic analysis. P.C. made essential feedback to the manuscript. All authors have approved the final article.
Received: 17 September 2021
Accepted: 13 January 2022
Article published online:
16 March 2022
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- 1 Skre H. Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin Genet 1974; 6 (02) 98-118
- 2 Timmerman V, Strickland AV, Züchner S. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Genes 2014; 5 (01) 13-32
- 3 Reilly MM, Murphy SM, Laurá M. Charcot-Marie-Tooth disease. J Peripher Nerv Syst 2011; 16 (01) 1-14
- 4 Davis CJ, Bradley WG, Madrid R. The peroneal muscular atrophy syndrome: clinical, genetic, electrophysiological and nerve biopsy studies. I. Clinical, genetic and electrophysiological findings and classification. J Genet Hum 1978; 26 (04) 311-349
- 5 Berciano J, García A, Gallardo E. et al. Intermediate Charcot-Marie-Tooth disease: an electrophysiological reappraisal and systematic review. J Neurol 2017; 264 (08) 1655-1677
- 6 Saporta AS, Sottile SL, Miller LJ, Feely SM, Siskind CE, Shy ME. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol 2011; 69 (01) 22-33
- 7 Fridman V, Bundy B, Reilly MM. et al. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry 2014; 0: 1-6
- 8 Ylikallio E, Johari M, Konovalova S. et al. Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot-Marie-Tooth neuropathy and a mutation in HSPB1. Eur J Hum Genet 2014; 22 (04) 522-527
- 9 Bacquet J, Stojkovic T, Boyer A. et al. Molecular diagnosis of inherited peripheral neuropathies by targeted next-generation sequencing: molecular spectrum delineation. BMJ Open 2018; 8 (10) e021632
- 10 Burns J, Ouvrier R, Estilow T. et al. Validation of the Charcot-Marie-Tooth disease pediatric scale as an outcome measure of disability. Ann Neurol 2012; 71 (05) 642-652
- 11 Gagnon C, Massie R, Tremblay M, Darcy S, Martel M, Burns J. Traduction française de l'échelle Charcot-Marie-Tooth Disease Pediatric Scale. Can J Neurol Sci 2017; 44 (06) 740-743
- 12 Cornett KM, Menezes MP, Bray P. et al. Inherited Neuropathies Consortium. Phenotypic variability of childhood Charcot-Marie-Tooth Disease. JAMA Neurol 2016; 73 (06) 645-651
- 13 Luigetti M, Fabrizi GM, Bisogni G. et al. Charcot-Marie-Tooth type 2 and distal hereditary motor neuropathy: clinical, neurophysiological and genetic findings from a single-centre experience. Clin Neurol Neurosurg 2016; 144: 67-71
- 14 Lin KP, Soong BW, Yang CC. et al. The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan. PLoS One 2011; 6 (12) e29393
- 15 Ryan CS, Conlee EM, Sharma R, Sorenson EJ, Boon AJ, Laughlin RS. Nerve conduction normal values for electrodiagnosis in pediatric patients. Muscle Nerve 2019; 60 (02) 155-160
- 16 Chung KW, Kim SB, Park KD. et al. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain 2006; 129 (Pt 8): 2103-2118
- 17 Bombelli F, Stojkovic T, Dubourg O. et al. Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features. JAMA Neurol 2014; 71 (08) 1036-1042
- 18 Pitt M. Paediatric electromyography in the modern world: a personal view. Dev Med Child Neurol 2011; 53 (02) 120-124