Ehlers-Danlos syndrome: recent advances and current understanding of the clinical and genetic heterogeneity.
The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of generalized connective tissue disorders, the major manifestations of which are skin fragility, skin hyperextensibility, and joint hypermobility. The clinical and molecular definition of more than ten types of EDS has, more than ever, emphasized the importance of correct diagnosis because the natural history and mode of inheritance differ among the types. Unfortunately, much of the older literature does not differentiate among the types clearly, and in some instances the life-threatening complications of EDS type IV may be cited as characteristic of the syndrome as a whole. Heterogeneity in EDS began to be appreciated about 30 years ago when the core of the modern classification was developed by Barabas. Since then it was extended by Beighton et al, and then amplified with the insights provided by biochemical and molecular genetic studies. Clinical studies were sufficient initially to distinguish five types of EDS; biochemical studies identified four additional types, EDS type VI, EDS type VII, EDS type IX, and EDS type X, whereas clinical criteria distinguished EDS type VIII. In the following sections, the clinical manifestations of the different forms of EDS are summarized and the known biochemical and molecular genetic features are emphasized.
Department of Pathology, University of Washington, Seattle 98195.
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D003094:Collagen / Q000235:genetics; D003300:Copper / Q000378:metabolism; D003880:Dermatology / Q000639:trends; D004535:Ehlers-Danlos Syndrome / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D005808:Genes, Recessive; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics
D003300:Copper; D003094:Collagen; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase