Molecular Genetics of Ehlers–Danlos Syndrome

Abstract

Abstract Ehlers–Danlos syndrome (EDS) subsumes a clinically and genetically heterogeneous group of rare connective tissue diseases, characterised by tissue fragility and a highly variable clinical spectrum involving skin, ligaments, joints, blood vessels and internal organs. Based on clinical criteria as well as genetic and biochemical data, the current Villefranche classification subdivides EDS into six major subtypes, which are caused by mutations in genes encoding fibrillar collagens or enzymes involved in collagen biosynthesis. Mutations in type V and type III collagen cause classic and vascular EDS, respectively, whereas mutations affecting the processing of type I collagen lead to the kyphoscoliotic, arthrochalasic and dermatosparactic EDS types. During the last years, specific biochemical and molecular investigations identified several new EDS variants and have brought new insights into the molecular pathogenesis of EDS. Establishing the correct EDS subtype has important implications for genetic counselling and management and offers the opportunity for clinical trials, which are still at the beginning. Key Concepts: EDS is a clinically and genetically heterogeneous group of connective tissue diseases. The Villefranche classification distinguishes six major EDS subtypes. The most frequent molecular causes in EDS are mutations in fibrillar collagens or enzymes involved in collagen metabolism. Recent and ongoing research is leading to the discovery of new EDS variants and to an improvement of understanding the molecular pathology of EDS. Defining the EDS subtype has an important value for the patient and is the basis for clinical management and possible future clinical trials.