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Background: The Ehlers-Danlos syndrome encompasses a group of hereditary disorders of the connective tissue, characterized by hyperextensible skin, joint hypermobility; and varying degrees of vessel and tissue fragility. The main forms are classical, hypermobile, vascular, kyphoscoliotic A/B, arthrochalasis A/B and dermatosparaxis types., Patients and Methods: We report our experience in diagnosis and classification of Ehlers-Danlos-syndrome, especially with the combination of clinical and morphological criteria, at the Department of Dermatology of the University of Heidelberg with more than 600 patients between 1984 and 2004., Results: We classified those types of EDS which are characterized by regular and characteristic ultrastructural changes in the dermal components, primarily collagen, including the classical, hypermobile and vascular types as well as the less-common arthrochalasis and dermatosparaxis types. The combination of clinical and morphologic features facilitates the selection of candidate genes for molecular genetic investigation., Conclusions: Besides the skin, skeleton and vessels, many other organ systems such as eyes and intestine, can be affected in Ehlers-Danlos syndrome. Accordingly, interdisciplinary cooperation (pediatrics, surgery, orthopedics, rheumatology, neurology, genetics) is necessary. As the connective tissue of the skin is accessible for biopsy and diagnostic investigation, dermatologists should be trained in the diagnostic approach and classification of this syndrome.

The Ehlers-Danlos syndrome (EDS) comprises a heterogenous group of nine hereditary connective tissue disorders, characterized by hyperelasticity of skin and hypermobility of joints to differing extents. The skin is easily injured and wound healing is delayed. The majority of EDS patients belong to EDS-types I-III. The pathogenesis in these cases is not known, although recent data suggest a role for collagen V. In contrast, the etiology of EDS-types IV, VI and VII has been found. While EDS IV is caused by a mutation in the collagen III gene, in EDS VI a mutation in the lysyl hydroxylase gene is present. In EDS VII, the underlying defect is a mutation in the collagen I gene. The EDS-types V, VII and X are very rare; their symptoms resemble those of EDS-type II.

Five patients with Ehlers-Danlos syndrome (EDS) were classified according to clinical and genetic criteria and were examined by electron microscopy: two cases in Type I and one case each in Types II, III, and V were found. In all cases distinct ultrastructural changes were seen in the fibroblasts and the collagen fibrils whereas the elastic fibers were normal, as shown with special staining techniques. a) The fibroblasts were smaller, their cytoplasmic processes reduced in number and size, the endoplasmic reticulum was underdeveloped and their ribosome content was diminished. Also, cellular degeneration up to necrosis was found. In three cases intercellular substances were seen, possibly indicating a prefibrillar secretion product of the fibroblasts. b) The collagen fibrils revealed a defective lateral aggregation with disturbances of their thickness growth. Characteristic are abnormal fibrils with star-shaped cross profiles and marginal serrations in longitudinal sections. Their periodicity, however, remained normal. In three cases (Types I, I, and V) scattered giant fibrils were also present. Generally, the bundling of collagen fibrils into fibers seemed to be loosened. These findings were common to all various types of EDS. Therefore, a classification was not possible according to criteria of electron microscopy. Ehlers-Danlos syndrome is a disease of fibroblasts leading to changes of dermal collagen.

Progress in the experimental field and a deepened understanding of biological functional entities gave considerable impetus to connective tissue research. This was particularly true for the heritable connective tissue disorders, of which the Ehlers-Danlos-Syndrome is the best example. Its clinical and biochemical heterogeneity have allowed a classification of the disease into sub-groups, and the conditions for differential diagnosis and therapeutic trials were thus improved.