[en] Ehlers-Danlos syndrome (EDS) is heterogenous with regard to genetic traits, clinical manifestation, the biomechanical and microscopic properties of connective tissues, and basic molecular defects. We report on nine relatives of four generations who suffered from large vessel dissections and cutaneous microscopic changes consistent with EDS. Measurements of the mechanical properties of skin were performed using a computerized suction device (Cutometer). Morphological and biomechanical alterations suggestive of EDS were present in all examined subjects. A loose network of collagen bundles was admixed with clumsy elastic fibres. Factor XIIIa-positive dermal dendrocytes looked almost normal but were slim and rarefied in four subjects. The severity in ultrastructural alterations of the collagen network differed among the subjects. The group with the most prominent changes showed the most striking biomechanical alterations characterized by increased biologic elasticity without any excess in skin extensibility. A positive correlation was found between skin extensibility and elasticity. In conclusion, distinct alterations in the collagen scaffolding were found to be correlated to variable severity in biomechanical alterations of the skin. The predictive value of these changes for large vessel dissections in some families at risk remains to be settled.
Disciplines :
Dermatology
Author, co-author :
Flagothier, Caroline ; Centre Hospitalier Universitaire de Liège - CHU > Dermatologie
Goffin, Véronique ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Hermanns-Lê, Trinh ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Pierard, Gérald ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Quatresooz, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Dermatopathologie
Language :
English
Title :
A four-generation Ehlers-Danlos syndrome with vascular dissections. Skin ultrastructure and biomechanical properties.
Beighton, P., De Paepe, A., Steinmann, B., Tsipouras, P. and Wenstrup, R.J., 1998, Ehlers Danlos syndromes. Revised nosology. Villefranche 1997, American Journal of Medical Genetics, 77, 31-37.
Hermanns-Lê , T. and Piérard, G.E., 2000, The Ehlers-Danlos syndrome, a revisited centenarian. Skin, 3, 138-141.
Burrows, N.P., 1999, The molecular genetics of Ehlers-Danlos syndrome. Clinical Experiments in Dermatology, 24, 99-106.
Holbrook, K.A. and Byers, P.H., 1982, Structural abnormalities in the dermal collagen and elastic matrix from the skin of patients with inherited connective tissue disorders. Journal of Investigative Dermatology, 79, 7S-11S.
Pierard, G.E., Pierard-Franchimont, C. and Lapiere, Ch.M., 1983, Histopathological aid at the diagnosis of the Ehlers-Danlos syndrome, gravis and mitis types. International Journal of Dermatology, 22, 300-304.
Pierard, G.E., Le, T., Pierard-Franchimont, C. and Lapiere, Ch.M., 1988, Morphometric study of cauliflower collagen fibrils in Ehlers Danlos syndrome type I. Collagen and Related Research, 8, 453-457.
Piérard, G.E., Hermanns-Lê , T., Arrese-Estrada, J., Piérard-Franchimont, C. and Lapière, Ch.M., 1993, Structure of the dermis in type VIIc Ehlers Danlos syndrome. American Journal of Dermatopathology, 15, 127-132.
Hausser, I. and Anton-Lamprecht, I., 1994, Differential ultrastructural aberration of collagen fibrils in Ehlers-Danlos syndrome types I-IV as a mean of diagnostics and classification. Human Genetics, 3, 394-407.
Kobayasi, T. and Ullman, S., 1995, Twisted collagen fibrils. Significance for diagnosis of Ehlers-Danlos syndrome. Journal of Investigative Dermatology, 107, 266.
Nuytinck, L.K., Freund, M.M. and Lagae, L.G., 2000, Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen. American Journal of Human Genetics, 66, 1395-1402.
Hermanns-Lê , T. and Piérard, G.E., 2001, Factor XIIIa-positive dendrocyte rarefaction in Ehlers-Danlos syndrome, classic type. American Journal of Dermatopathology, 23, 427-430.
Hermanns-Lê , T., Piérard, G. and Quatresooz, P., 2005, Ehlers-Danlos like dermal abnormalities in women with recurrent preterm premature rupture of the fetal membranes. American Journal of Dermatopathology, 5, 407-410.
Graham, R. and Beighton, P., 1969, Physical properties of the skin in Ehlers-Danlos syndrome. Annals of the Rheumatic Diseases, 28, 246-250.
Bramont, C., Vasselet, R., Rochefort, A. and Agache, P., 1988, Mechanical properties of the skin in Marfan's syndrome and Ehlers-Danlos syndrome. Bioengineering and the Skin, 4, 217-227.
Henry, F., Goffin, V., Piérard-Franchimont, C. and Piérard, G.E., 1996, Mechanical properties of skin in Ehlers-Danlos syndrome, types I, II and III. Pediatric Dermatology, 13, 464-467.
Pierard, G.E. and EEMCO Group, 1999, EEMCO guidance to the in vivo assessment of tensile functional properties of the skin. Part 1, Relevance to the structures and ageing of the skin and subcutaneous tissues. Skin Pharmacology and Applied Skin Physiology, 12, 352-362.
Pepin, M., Schwarze, U., Superti-Furga, A. and Byers, P.H., 2000, Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. New England Journal of Medicine, 342, 673-680.
Brandt, T., Hausser, I., Orbek, E., Grau, A., Hartschuh, W., Anton-Lamprecht, I. and Hacke, W., 1998, Ultrastructural connective tissue abnormalities in patients with spontaneous cervicocerebral artery dissections. Annals of Neurology, 44, 281-285.
Brandt, T., Orberk, E., Weber, R., Werner, I., Busse, O., Muller, B.T., Wigger, F., Grau, A., Grond-Ginsbach, C. and Hausser, I., 2001, Pathogenesis of cervical artery dissections. Association with connective tissue abnormalities. Neurology, 57, 24-30.
Brandt, T. and Grond-Ginsbach, C., 2002, Spontaneous cervical artery dissections. From risk factors toward pathogenesis. Stroke, 33, 657-658.
Grond-Ginsbach, C., Schnippering, H., Hausser, I., Weber, R., Werner, I., Steiner, H.H., Luttgen, N., Busse, O., Grau, A. and Brandt, T., 2002, Ultrastructural connective tissue aberrations in patients with intracranial aneurysms. Stroke, 33, 2192-2196.
Ulbricht, D., Diederich, N.J., Hermanns-Lê , T., Metz, R.J., Macian, F. and Piérard, G.E., 2004, Cervical artery dissection, an atypical presentation in Ehlers-Danlos-like collagen pathology? Neurology, 63, 1708-1710.
Pierard-Franchimont, C., Nikkels-Tassoudji, N., Lefebvre, P. and Pierard, G.E., 1998, Subclinical skin stiffening in adults suffering from type 1 diabetes mellitus. A comparison with Raynaud's syndrome. Journal of Medical Engineering & Technology, 22, 206-210.
Pierard, G.E., Nizet, J.L., Adant, J.P., Avila Amacho, M., Pans, A. and Fissette, J., 1999, Tensile properties of relaxed excised skin exhibiting striae distensae. Journal of Medical Engineering & Technology, 23, 69-72.
Fournier, R. and Pierard, G.E., 2000, Skin tensile strength modulation by compressive garments in burn patients. A pilot study. Journal of Medical Engineering & Technology, 24, 277-280.
Piérard, G.E., Vanderplaetsen, S. and Piérard-Franchimont, C., 2001, Comparative effect of hormone replacement therapy on bone mass density and skin tensile properties. Maturitas, 40, 221-227.
Piérard, G.E., Piérard-Franchimont, C., Vanderplaetsen, S., Franchimont, N., Gaspard, U. and Malaise, M., 2001, Relationship between bone mass density and tensile strength of the skin in women. European Journal of Clinical Investigation, 31, 731-735.
Oxlung, H., 1986, Relationship between the biomechanical properties, composition and molecular structure of connective tissues. Connective Tissue Research, 15, 65-72.