Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Ehlers-Danlos Syndrome Arthrochalasis Type (EDS type VIIA und VIIB) [Q79.6]

OMIM numbers: 130060, 120150 (COL1A1), 120160 (COL1A2)

Dr. rer. nat. Karin Mayer

Scientific Background

The very rare EDS type VIIA/B (arthrochalasis) is inherited in an autosomal dominant pattern. An extreme, generalized hypermobility of the joints associated with joint subluxations as well as congenital bilateral hip luxation is characteristic. Mutations in the collagen genes COL1A1 and COL1A2 are causal for the disease. They code for the α1 and α2 chains of the type I collagen which constitutes the predominant collagen in skin and bones.

Almost all of the described mutations so far affect exon 6 of the COL1A1 gene (EDS type VIIA) or of the COL1A2 gene (EDS type VIIB).These are mainly splice mutations, but also genomic deletions, whereby the recognition site for the cleavage of the N-terminal propeptides in the α chains of type I procollagen is eliminated in any case. Incomplete processed procollagen chains can also be detected biochemically and electron-microscopically by a characteristic ultrastructure. So far only few mutations have been reported outside of this defined region in EDS type VIIA/B, however affected patients also showed symptoms of osteogenesis imperfecta. Most common are mutations in the COL1A2 gene, which are associated with a congenital hip luxation and other joint instabilities. Mutations in COL1A1 are rarely the cause of EDS type VII. Since two α1 chains and one α2 chain form a heterotrimer, a more severe phenotype is expected by COL1A1 mutations in EDS type VIIA than in EDS Type VIIB.