Pathogenic mechanisms in genetically defined Ehlers-Danlos syndromes

Trends Mol Med. 2024 Sep;30(9):824-843. doi: 10.1016/j.molmed.2024.06.001. Epub 2024 Aug 14.

Abstract

The Ehlers-Danlos syndromes (EDS) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis.

Keywords: Ehlers–Danlos syndromes; collagen; extracellular matrix; fibroblast; pathomechanisms.

Publication types

  • Review

MeSH terms

  • Animals
  • Collagen / genetics
  • Collagen / metabolism
  • Ehlers-Danlos Syndrome* / genetics
  • Ehlers-Danlos Syndrome* / metabolism
  • Ehlers-Danlos Syndrome* / pathology
  • Extracellular Matrix* / metabolism
  • Humans
  • Mutation

Substances

  • Collagen