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

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Ehlers-Danlos Syndrome classical Type (EDS types I and II) [Q79.6]

OMIM numbers: 130000, 120215 (COL5A1), 130010, 120190 (COL5A2)

Dr. rer. nat. Karin Mayer

Scientific Background

EDS type I/II (classical type) is inherited in an autosomal dominant pattern. With a frequency of 1 in 20,000 it is the second most common type of EDS. EDS type I gravis and EDS type II mitis differ only in the degree of severity. Major clinical criteria include hyperelastic skin, atrophic scars (cigarette paper scars) in sequelae of tissue fragility and articular (joint) hypermobility. Minor criteria include soft velvety skin, molluscoid pseudotumors, subcutaneous spheroids as well as complications of the musculoskeletal system due to the hypermobility and surgical complications owing to tissue fragility. EDS type I gravis presents with generalized skin and skeletal manifestations, there is a risk of rupture of internal organs. In EDS type II mitis joint hypermobility is commonly limited to the extremities and skin manifestation are usually mild.

The genetic cause of EDS type I and II so far known are mutations in the COL5A1 and COL5A2 gene which code for the α1- and α2 chain of type V collagen. Two α1 chains and one α2 chain form type V collagen heterotrimers which play a key role in the biosynthesis of collagen fibrils. In approx. 40% of patients with EDS type I and II mutations in the COL5A1 gene can be identified, approx. 8% show a mutation in the COL5A2 gene. In more than 90% of patients that fulfill all major criteria of the Villefranche nosology COL5A1 and COL5A2 mutations can be detected. In a few cases mutations in the COL1A1 gene were found, however, most of these patients also showed symptoms of osteogenesis imperfecta. The majority of all COL5A1 and COL5A2 mutations are translational stop mutations causing a null-allel, approx. 30% of all COL5A1 mutations and 40% of all COL5A2 mutations are structural mutations affecting glycine in the triple helix. Genomic deletions in the COL5A1 and the COL5A2 gene have not been described so far, only one genomic duplication was identified up to now. Electron microscopic detection of abnormal collagen fibril structure can support clinical diagnosis.