Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type

Genet Med. 2010 Oct;12(10):597-605. doi: 10.1097/GIM.0b013e3181eed412.


Classic Ehlers-Danlos syndrome is a heritable connective tissue disorder characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. It comprises Ehlers-Danlos syndrome type I and Ehlers-Danlos syndrome type II, but it is now apparent that these form a continuum of clinical findings and differ only in phenotypic severity. It is currently estimated that approximately 50% of patients with a clinical diagnosis of classic Ehlers-Danlos syndrome harbor mutations in the COL5A1 and the COL5A2 gene, encoding the α1 and the α2-chain of type V collagen, respectively. However, because no prospective molecular studies of COL5A1 and COL5A2 have been performed in a clinically well-defined patient group, this number may underestimate the real proportion of patients with classic Ehlers-Danlos syndrome harboring a mutation in one of these genes. In the majority of patients with molecularly characterized classic Ehlers-Danlos syndrome, the disease is caused by a mutation leading to a nonfunctional COL5A1 allele and resulting in haploinsufficiency of type V collagen. A smaller proportion of patients harbor a structural mutation in COL5A1 or COL5A2, causing the production of a functionally defective type V collagen protein. Most mutations identified so far result in a reduced amount of type V collagen in the connective tissues available for collagen fibrillogenesis. Inter- and intrafamilial phenotypic variability is observed, but no genotype-phenotype correlations have been observed. No treatment for the underlying defect is presently available for Ehlers-Danlos syndrome. However, a series of preventive guidelines are applicable.

Publication types

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

MeSH terms

  • Collagen Type V / genetics*
  • Connective Tissue / physiopathology*
  • Contusions
  • Ehlers-Danlos Syndrome* / diagnosis
  • Ehlers-Danlos Syndrome* / epidemiology
  • Ehlers-Danlos Syndrome* / genetics
  • Ehlers-Danlos Syndrome* / physiopathology
  • Ehlers-Danlos Syndrome* / therapy
  • Genotype
  • Haploinsufficiency
  • Humans
  • Joint Instability
  • Mutation
  • Phenotype


  • COL5A1 protein, human
  • Collagen Type V