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Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes

  • Tanya Stojkovic
    Correspondence
    Corresponding author at: Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France.
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France

    Centre de Recherche en Myologie, Sorbonne Université-Inserm UMRS974, Paris, France
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  • Marion Masingue
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France
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  • Helène Turmel
    Affiliations
    Department of Neurophysiology, APHP, Pitié Salpetrière hospital, Paris, France
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  • Marianne Hezode-Arzel
    Affiliations
    Department of Neurophysiology, APHP, Pitié Salpetrière hospital, Paris, France
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  • Anthony Béhin
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France
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  • Sarah Leonard-Louis
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France
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  • Guillaume Bassez
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France

    Centre de Recherche en Myologie, Sorbonne Université-Inserm UMRS974, Paris, France
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  • Stéphanie Bauché
    Affiliations
    Centre de Recherche en Myologie, Sorbonne Université-Inserm UMRS974, Paris, France
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  • Patricia Blondy
    Affiliations
    National Reference Center for Muscle Channelopathies, APHP, Pitié Salpetrière hospital, Paris, France

    Biochemistry Department, Center of Molecular and Cellular Genetics, APHP, Pitié Salpetrière hospital, Paris, France
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  • Pascale Richard
    Affiliations
    Biochemistry Department, Center of Molecular and Cellular Genetics, APHP, Pitié Salpetrière hospital, Paris, France
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  • Damien Sternberg
    Affiliations
    National Reference Center for Muscle Channelopathies, APHP, Pitié Salpetrière hospital, Paris, France

    Biochemistry Department, Center of Molecular and Cellular Genetics, APHP, Pitié Salpetrière hospital, Paris, France
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  • Bruno Eymard
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France
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  • Author Footnotes
    1 Last co-authors
    Emmanuel Fournier
    Footnotes
    1 Last co-authors
    Affiliations
    Department of Neurophysiology, APHP, Pitié Salpetrière hospital, Paris, France

    National Reference Center for Muscle Channelopathies, APHP, Pitié Salpetrière hospital, Paris, France

    Department of Physiology, Sorbonne University, Faculté de médecine Pitié-Salpêtrière, Paris, France
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  • Author Footnotes
    1 Last co-authors
    Rocío Nur Villar-Quiles
    Footnotes
    1 Last co-authors
    Affiliations
    Reference Center for Neuromuscular Disorders (Nord/Est/Ile de France), Institute of Myology, Pitié-Salpêtrière Hospital, APHP, Pitié-Salpêtrière Hospital, Paris, France

    Centre de Recherche en Myologie, Sorbonne Université-Inserm UMRS974, Paris, France
    Search for articles by this author
  • Author Footnotes
    1 Last co-authors
Published:October 09, 2022DOI:https://doi.org/10.1016/j.nmd.2022.10.001

      Highlights

      • Interpretation of novel or unknown significance variants in CMS-related genes is challenging.
      • We propose a simple, painless ENMG protocol based on 3Hz-repetitive nerve stimulation.
      • 5 ENMG patterns based on the presence of R-CMAPs and the distribution of decrements in selected muscles.
      • ENMG patterns significantly correlated with the genetic findings.
      • This algorithm may improve diagnosis and therapeutic monitoring in CMS patients.

      Abstract

      Congenital myasthenic syndromes (CMS) are a group of heterogeneous diseases of the neuromuscular junction. We report electrodiagnostic testing (EDX) and genetic findings in a series of 120 CMS patients tested with a simple non-invasive EDX workup with surface recording of CMAPs and 3Hz repetitive nerve stimulation of accessory, radial and deep fibular nerves. Five ENMG phenotypes were retrieved based on the presence or not of R-CMAPs and the distribution pattern of decremental CMAP responses which significantly correlated with genetic findings (p <0.00001). R-CMAPs were found in all COLQ-mutated patients (CMS1A) and Slow Channel CMS (SCCMS) (CMS1B). CMS1A exhibited greater decrements in accessory nerve RNS than CMS1B. Patients without R-CMAPs were classified into CMS2A (DOK7-, MUSK-, GFPT1-, GMPPB-, TOR1AIP-mutated) when exhibiting predominant accessory nerve RNS decrements, CMS2B (CHRNE, CHRND, RAPSN) with predominant radial nerve RNS decrements, or CMS2C (AGRN) if there were predominant fibular decrements. Our algorithm may have a major impact on diagnostic and therapeutic monitoring in CMS patients, as well as for validation of the pathogenicity of genetic variants. It should also be part of the evaluation of unexplained muscle weakness or complex neuromuscular phenotypes.

      Keywords

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