Introduction: Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy with an impact on patients' quality of life and wide genetic heterogeneity. Next-generation sequencing (NGS) has extended the molecular diagnosis. This study aims to describe a cohort of patients with CMT onset in childhood to explore genotype-phenotype correlations.
Material and methods: This is a retrospective and single-center study. Between 1992 and 2016, patients with CMT diagnosed in childhood and a molecular diagnosis were included. The follow-up was done at the Marseille Timone Teaching hospital and symptoms were retrieved over time in the patients' files, as well as from molecular data and an electrodiagnostic exam. We distinguished three groups: PMP22 compared CMT (CMT1A), MFN2 compared CMT (CMT2A2) and "all genes except PMP22".
Results: Seventy-five patients were included with 11 different genes involved, PMP22 being the most frequent (61.3%), then MFN2 (14.7%) and other sporadic mutations in various genes. Limitations in walking tended to occur earlier and more often, and distal strength impairment tended to progress further in CMT2A2 and "others genes than PMP22". The mean age at diagnosis was 8.4 years with a mean age when parents first expressed concern of 4.1 years. Only three patients lost their ability to walk. We describe two cases of digenism and one case of GAN mutation with a CMT-like presentation. An electromyogram was not systemically performed.
Conclusion: There is a wide genetic and clinical heterogeneity in CMT. We tend to describe more severe patterns in CMT2A2 and less progressive presentations in CMT1A considering distal strength impairment and limitations walking. Prospective studies with more objective principal judgement criteria would be necessary to confirm these observations.
Keywords: Charcot-Marie-Tooth disease; Genotype–phenotype correlations; Peripheral inherited neuropathy.
Copyright © 2018. Published by Elsevier Masson SAS.