| Signs in Ehlers-Danlos Syndromes: The role of skin findings in determining the clinical diagnosis |
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W. Chen, J. Yang, B. Griswold, A. Gustafson, M. Burchett, C.A. Francomano, N.B. McDonnell Ehlers-Danlos Syndromes (EDS) are a group of genetically heterogeneous hereditary disorders of connective tissue manifesting with joint hypermobility, tissue and vessel fragility, and skin involvement. Differentiation between subtypes of EDS has proven to be a challenge on a clinical basis. We present a summary of skin findings in 100 consecutive patients with a diagnosis of EDS enrolled in a natural history study at the NIH. Skin findings were notable for intra-familial variability. Presence of atrophic scars and skin hyperextensibility were variable not only between members of a family, but also on different body parts of the same person. Smooth and velvety skin, which is highly subjective, was noted in many patients, however unaffected members of some families were found to have the velvety skin, casting doubt in the clinical utility of this finding. Bruising, translucent skin, subcutenous venous patterns, and poor wound healing were seen to varying extents in patients with vascular EDS, but were also noted in other subtypes. Patients with a clinical history consistent with the hypermobile form were found to have a youthful appearance, a non-quantifiable finding. Molecular studies of COL5A1 and COL5A2 were completed on a research basis on patients who had skin features suggestive of the classical form of EDS (29/100), such as the presence of skin hyperextensibility, widened atrophic scars, and poor wound healing. Five mutations were found in COL5A1 and no mutations were found in COL5A2. By contrast, a sixteen-year-old girl, and a sixty-year-old woman, both with joint hypermobility, chronic joint pain and extensive striae similar to that seen in Marfan syndrome were found to have mutations in N-terminal propeptide of COL5A1. Our results suggest that while the presence of a skin abnormality can help to point to the diagnosis of EDS, skin findings from a single affected family member are often not helpful in determining the clinical subtype or predicting the molecular defect involved.
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