Neuromuscular involvement in various types of Ehlers–Danlos syndrome

Authors

  • Nicol C. Voermans MD,

    Corresponding author
    1. Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
    • Neuromuscular Centre Nijmegen, Department of Neurology, 935, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
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  • Nens van Alfen PhD,

    1. Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
    2. Department of Clinical Neurophysiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Sigrid Pillen MD,

    1. Department of Clinical Neurophysiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Martin Lammens PhD,

    1. Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
    2. Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Joost Schalkwijk PhD,

    1. Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Machiel J. Zwarts PhD,

    1. Department of Clinical Neurophysiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Iris A. van Rooij PhD,

    1. Department of Epidemiology, Biostatistics, and Health Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Ben C. J. Hamel PhD,

    1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Baziel G. van Engelen PhD

    1. Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
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  • Potential conflict of interest: Nothing to report.

Abstract

Objective

Ehlers–Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between muscle cells and extracellular matrix molecules; however, muscle symptoms are only sporadically reported. We designed a cross-sectional study to find out whether neuromuscular features are part of EDS.

Methods

Standardized questionnaires, physical examination, nerve conduction studies, electromyography, muscle ultrasound, and muscle biopsy were performed in 40 EDS patients with the vascular, classic, tenascin-X (TNX)–deficient type EDS, and hypermobility type of EDS caused by TNXB haploinsufficiency.

Results

Muscle weakness, myalgia, and easy fatigability were reported by the majority of patients. Mild-to-moderate muscle weakness (85%) and reduction of vibration sense (60%) were common. Nerve conduction studies demonstrated axonal polyneuropathy in five patients (13%). Needle electromyography myopathic features in nine patients (26%) and a mixed neurogenic-myopathic pattern in most (60%). Muscle ultrasound showed increased echo-intensity (48%) and atrophy (50%). Mild myopathic features were seen on muscle biopsy of five patients (28%). Overall, patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected.

Interpretation

Mild-to-moderate neuromuscular involvement is common in various types of EDS, with a remarkable relation between residual TNX level and degree of neuromuscular involvement, compatible with a dose–effect relation. The findings of this study should increase awareness of neuromuscular symptoms in EDS patients and improve clinical care. They also point to a role of the extracellular matrix in muscle and peripheral nerve function. This is an updated version of this article that originally published online on June 29, 2009. Ann Neurol 2009;65:687–697

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