Molecular Genetics and Pathogenesis of Ehlers-Danlos Syndrome and Related Connective Tissue Disorders

Genes (Basel). 2020 May 13;11(5):547. doi: 10.3390/genes11050547.


Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders (HCTDs) characterized by a variable degree of skin hyperextensibility, joint hypermobility and tissue fragility. The current EDS classification distinguishes 13 subtypes and 19 different causal genes mainly involved in collagen and extracellular matrix synthesis and maintenance. EDS need to be differentiated from other HCTDs with a variable clinical overlap including Marfan syndrome and related disorders, some types of skeletal dysplasia and cutis laxa. Clinical recognition of EDS is not always straightforward and for a definite diagnosis, molecular testing can be of great assistance, especially in patients with an uncertain phenotype. Currently, the major challenging task in EDS is to unravel the molecular basis of the hypermobile EDS that is the most frequent form, and for which the diagnosis is only clinical in the absence of any definite laboratory test. This EDS subtype, as well as other EDS-reminiscent phenotypes, are currently investigated worldwide to unravel the primary genetic defect and related pathomechanisms. The research articles, case report, and reviews published in this Special Issue focus on different clinical, genetic and molecular aspects of several EDS subtypes and some related disorders, offering novel findings and future research and nosological perspectives.

Keywords: Ehlers–Danlos syndrome; differential diagnosis; heritable connective tissue disorders; integrated omics approaches; next generation sequencing (NGS); transcriptomics.

Publication types

  • Editorial
  • Introductory Journal Article

MeSH terms

  • Connective Tissue Diseases / classification
  • Connective Tissue Diseases / diagnosis
  • Connective Tissue Diseases / genetics
  • Diagnosis, Differential
  • Ehlers-Danlos Syndrome / classification
  • Ehlers-Danlos Syndrome / diagnosis
  • Ehlers-Danlos Syndrome / genetics*
  • Genetic Heterogeneity
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Diagnostic Techniques
  • Phenotype