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.