Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type.
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.
Malfait
Fransiska
F
Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Wenstrup
Richard J
RJ
De Paepe
Anne
A
D024062:Collagen Type V / Q000235:genetics*; D003238:Connective Tissue / Q000503:physiopathology*; D003288:Contusions; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D005838:Genotype; D057895:Haploinsufficiency; D006801:Humans; D007593:Joint Instability; D009154:Mutation; D010641:Phenotype
C530725:COL5A1 protein, human; D024062:Collagen Type V