The Ehlers-Danlos syndrome, a disorder with many faces

• Published in: Clinical genetics 2012-07, Vol.82 (1), p.1-11
• Main Authors: De Paepe, A, Malfait, F
• Format: Article
• Language: English
• Subjects: arterial fragility; Biological and medical sciences; Blood Vessels - metabolism; Blood Vessels - pathology; Collagen; Collagen - genetics; Danlos syndrome; Ehlers; Ehlers-Danlos Syndrome - classification; Ehlers-Danlos Syndrome - diagnosis; Ehlers-Danlos Syndrome - genetics; Ehlers-Danlos Syndrome - pathology; Extracellular Matrix - genetics; Fundamental and applied biological sciences. Psychology; Genes; Genetic Counseling; Genetic disorders; Genetic Heterogeneity; Genetics of eukaryotes. Biological and molecular evolution; Humans; joint hyperlaxity; Joints - metabolism; Joints - pathology; Medical genetics; Medical sciences; Molecular and cellular biology; molecular pathogenesis; Mutation; natural history; Protein Processing, Post-Translational; Proteoglycans - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - metabolism; Skin - pathology; Tenascin - genetics; wound healing
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2012.01858.x

The Ehlers–Danlos syndromes (EDSs) comprise a heterogeneous group of diseases, characterized by fragility of the soft connective tissues and widespread manifestations in skin, ligaments, joints, blood vessels and internal organs. The clinical spectrum varies from mild skin and joint hyperlaxity to severe physical disability and life‐threatening vascular complications. The current Villefranche classification recognizes six subtypes, most of which are linked to mutations in genes encoding fibrillar collagens or enzymes involved in post‐translational modification of these proteins. Mutations in type V and type III collagen cause classic or vascular EDS respectively, while mutations involving the processing of type I collagen are involved in the kyphoscoliosis, arthrochalasis and dermatosparaxis type of EDS. Establishing the correct EDS subtype has important implications for genetic counseling and management and is supported by specific biochemical and molecular investigations. Over the last years, several new EDS variants have been characterized which call for a refinement of the Villefranche classification. Moreover, the study of these diseases has brought new insights into the molecular pathogenesis of EDS by implicating genetic defects in the biosynthesis of other extracellular matrix (ECM) molecules, such as proteoglycans and tenascin‐X, or genetic defects in molecules involved in intracellular trafficking, secretion and assembly of ECM proteins.