Towards a functional pathology of hereditary neuropathies

Abstract

A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype–phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves. In several instances the lesion patterns are directly or indirectly linked to the known functions of the mutated gene. The present review is designed to provide an overview on these characteristic patterns. It also considers other aspects important for the manifestation and pathology of hereditary neuropathies including the role of inflammation, effects of chemotherapeutic agents and alterations detectable in skin biopsies.

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Acknowledgements

The authors are grateful to Mrs. H. Mader, Mrs. E. Beck and Mrs. C. Krude (Institute of Neuropathology, RWTH Aachen University Medical School) for technical assistance and to Mr. M. Meyenberg (Dept. of Cardiology, RWTH Aachen University Medical School) for artwork. This study was supported by grants from the German Research Foundation (DFG WE1406/13-1, to JW), the German Ministry for Education and Research (BMBF 01GM1511D, to JW, IK and JS), the Fritz-Thyssen-Stiftung (Az. 10.15.1.021MN, to JS) and the Interdisciplinary Center for Clinical Research (IZKF) within the Faculty of Medicine of RWTH Aachen University (N5-3, to JW, and N5-4, to JS). JW, IK and JS are members of the German CMT-Network which is supported by the German Federal Ministry of Education and Research (BMBF). JW is also a member of the German Motor Neuron Disease Network (MND-Net) sponsored by the BMBF and the German Society for Muscle Diseases (DGM).

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Weis, J., Claeys, K.G., Roos, A. et al. Towards a functional pathology of hereditary neuropathies. Acta Neuropathol 133, 493–515 (2017). https://doi.org/10.1007/s00401-016-1645-y

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Keywords

  • Charcot–Marie–Tooth disease (CMT)
  • Hereditary sensory and motor neuropathy (HMSN)
  • Hereditary motor neuropathy (HMN)
  • Hereditary sensory and autonomic neuropathy (HSAN)
  • Inflammatory neuropathy
  • Chemotherapy