Towards a functional pathology of hereditary neuropathies

Acta Neuropathol. 2017 Apr;133(4):493-515. doi: 10.1007/s00401-016-1645-y. Epub 2016 Nov 28.


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.

Keywords: Charcot–Marie–Tooth disease (CMT); Chemotherapy; Hereditary motor neuropathy (HMN); Hereditary sensory and autonomic neuropathy (HSAN); Hereditary sensory and motor neuropathy (HMSN); Inflammatory neuropathy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hereditary Sensory and Motor Neuropathy / drug therapy
  • Hereditary Sensory and Motor Neuropathy / genetics
  • Hereditary Sensory and Motor Neuropathy / pathology*
  • Hereditary Sensory and Motor Neuropathy / physiopathology*
  • Humans