Understanding the basis of Ehlers-Danlos syndrome in the era of the next-generation sequencing

Arch Dermatol Res. 2019 May;311(4):265-275. doi: 10.1007/s00403-019-01894-0. Epub 2019 Mar 2.

Abstract

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. The latest EDS classification recognized 13 subtypes in which the clinical and genetic phenotypes are often overlapping, making the diagnosis rather difficult and strengthening the importance of the molecular diagnostic confirmation. New genetic techniques such as next-generation sequencing (NGS) gave the opportunity to identify the genetic bases of unresolved EDS types and support clinical counseling. To date, the molecular defects have been identified in 19 genes, mainly in those encoding collagen, its modifying enzymes or other constituents of the extracellular matrix (ECM). In this review we summarize the contribution of NGS technologies to the current knowledge of the genetic background in different EDS subtypes.

Keywords: Ehlers–Danlos syndrome; Heritable connective tissue disorders; Heterogeneity.

Publication types

  • Review

MeSH terms

  • Collagen / genetics*
  • Collagenases / genetics
  • Connective Tissue / physiology*
  • Ehlers-Danlos Syndrome / diagnosis
  • Ehlers-Danlos Syndrome / genetics*
  • Extracellular Matrix Proteins / genetics
  • Genetic Counseling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Joint Instability
  • Joints / pathology*
  • Mutation / genetics
  • Pathology, Molecular
  • Phenotype
  • Skin / pathology*

Substances

  • Extracellular Matrix Proteins
  • Collagen
  • Collagenases