Abnormal oral vascular network geometric complexity in Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) leads to impaired extracellular matrix (ECM) structure. Since ECM plays a major role in blood vessel geometry, we tested the hypothesis of an abnormal geometrical complexity of the visible microvascular network in EDS. Twelve patients with EDS-II or EDS-III and a control population (n=12) were examined. The geometry characteristics for the networks on the lower vestibular oral mucosa were analyzed using high-resolution photographic images. Fractal dimension, D, at 2 scales (D 1-46 and D 1-15), blood vessel tortuosity (minimum-path fractal dimension , Dmin ), and relative Lempel-Ziv complexity (L-Z) values were determined. EDS vascular networks exhibited significantly higher D 1-46 (P <.00001) and D 1-15 (P <.00001), as well as L-Z complexity (P <.00001), together with lower Dmin values (P=.0001) than controls. These findings indicate the presence of a previously unrecognized microvascular network abnormality on the oral mucosa in EDS patients, and provide an additional phenotypical marker for the condition.

[1]  Dietmar Saupe,et al.  Chaos and fractals - new frontiers of science , 1992 .

[2]  R. Weksberg,et al.  Abnormal extracellular matrix in Ehlers‐Danlos syndrome type IV due to the substitution of glycine 934 by glutamic acid in the triple helical domain of type III collagen , 1996, Clinical genetics.

[3]  F. Ramirez,et al.  Elastic and collagenous networks in vascular diseases. , 2000, Cell structure and function.

[4]  A. Barducci,et al.  Abnormal oral mucosal light reflectance: a new clinical sign of Ehlers-Danlos syndrome. , 2004, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[5]  D. Barron,et al.  Ehlers-Danlos syndrome. , 1999, The Journal of pediatrics.

[6]  N. Suwa.  Supracellular structural principle and geometry of blood vessels , 2005, Virchows Archiv A.

[7]  W. Moore,et al.  Vascular manifestations in patients with Ehlers-Danlos syndrome. , 1982, Archives of surgery.

[8]  R. Cortvrindt,et al.  Confocal microscopy: principles and applications to the field of reproductive biology. , 2001, Folia histochemica et cytobiologica.

[9]  G. Latini,et al.  Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome , 2003, Gut.

[10]  Robert J. Gorlin,et al.  Syndromes of the Head and Neck , 1976 .

[11]  Yves Létourneau,et al.  Oral manifestations of Ehlers-Danlos syndrome. , 2001, Journal.

[12]  A. Lumsden,et al.  Vascular complications in Ehlers-Danlos syndrome. , 1994, The American surgeon.

[13]  A. Wahab,et al.  A new type of Ehlers‐Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar , 2003, Acta paediatrica.

[14]  P. Byers,et al.  Structural abnormalities in the dermal collagen and elastic matrix from the skin of patients with inherited connective tissue disorders. , 1982, The Journal of investigative dermatology.

[15]  R. J. Valentine,et al.  Remote vascular catastrophes after neurovascular interventional therapy for type 4 Ehlers-Danlos Syndrome. , 2000, AJNR. American journal of neuroradiology.

[16]  P. Toti,et al.  Absence of the inferior labial and lingual frenula in Ehlers-Danlos syndrome , 2001, The Lancet.

[17]  H. Kurz,et al.  Multivariate Characterization of Blood Vessel Morphogenesis in the Avian Chorioallantoic Membrane (CAM): Cell Proliferation, Length Density and Fractal Dimension , 1994 .

[18]  I. Eriksson,et al.  Vascular complications in the Ehlers-Danlos syndrome. , 1983, Acta chirurgica Scandinavica.

[19]  D. Rumoro,et al.  Fatal vascular catastrophe in Ehlers-Danlos syndrome: a case report and review. , 1996, The Journal of emergency medicine.

[20]  E. Ritz,et al.  The arteriovenous fistula. , 2003, Journal of the American Society of Nephrology : JASN.

[21]  P. Byers,et al.  Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome. , 1979, Laboratory investigation; a journal of technical methods and pathology.

[22]  E Oczeretko,et al.  Fractal geometric analysis of lung cancer angiogenic patterns. , 2001, Folia histochemica et cytobiologica.

[23]  P. Byers,et al.  Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I. , 2002, American journal of human genetics.

[24]  Albert-László Barabási,et al.  Life's Complexity Pyramid , 2002, Science.

[25]  Abraham Lempel,et al.  A universal algorithm for sequential data compression , 1977, IEEE Trans. Inf. Theory.

[26]  Bruce J. West,et al.  Chaos and fractals in human physiology. , 1990, Scientific American.

[27]  Anastasios A. Panagiotis A. Tsonis,et al.  Fractals: A New Look at Biological Shape and Patterning , 2015, Perspectives in biology and medicine.

[28]  T. Rasmussen,et al.  Ehlers-Danlos syndrome type IV and a novel mutation of the type III procollagen gene as a cause of abdominal apoplexy. , 2002, Mayo Clinic proceedings.

[29]  Dominique P Germain,et al.  Clinical and Genetic Features of Vascular Ehlers-Danlos Syndrome , 2002, Annals of vascular surgery.

[30]  Lee Goldman,et al.  Cecil Textbook of Medicine , 1985 .

[31]  M. R. Roach,et al.  Vascular collagen fibril morphology in type IV Ehlers-Danlos syndrome. , 1991, Connective tissue research.

[32]  D E Ingber,et al.  Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix , 1989, The Journal of cell biology.

[33]  Edda Klipp,et al.  Systems Biology , 1994 .

[34]  C. Karkos,et al.  Rupture of the Abdominal Aorta in Patients with Ehlers-Danlos Syndrome , 2000, Annals of vascular surgery.

[35]  U. Francke,et al.  Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders. , 1995, American journal of medical genetics.

[36]  P. Beighton,et al.  Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). , 1998, American journal of medical genetics.

[37]  H. Lynch,et al.  Diagnosing Lynch syndrome: is the answer in the mouth? , 2003, Gut.

[38]  Berk,et al.  Scale-invariant behavior and vascular network formation in normal and tumor tissue. , 1995, Physical review letters.

[39]  D. Silver,et al.  The Ehlers-Danlos Specter Revisited , 2002, Vascular and endovascular surgery.

[40]  Benoit B. Mandelbrot,et al.  Fractal Geometry of Nature , 1984 .

[41]  D. Valle,et al.  Online Mendelian Inheritance In Man (OMIM) , 2000, Human mutation.

[42]  Schuster,et al.  Easily calculable measure for the complexity of spatiotemporal patterns. , 1987, Physical review. A, General physics.

[43]  Fractal Dimension of Lymphocytic Nuclear Membrane in Mycosis Fungoides and Chronic Dermatitis , 1998 .

[44]  A Ettl,et al.  Corneal vascularisation and its relation to the physical properties of the tissue: a fractal analysis. , 1995, Current eye research.

[45]  K. Michalickova,et al.  Mutations of the alpha2(V) chain of type V collagen impair matrix assembly and produce ehlers-danlos syndrome type I. , 1998, Human molecular genetics.

[46]  H. E. Stanley,et al.  The fractal dimension of the minimum path in two- and three-dimensional percolation , 1988 .

[47]  H. Lynch,et al.  Ehlers-Danlos syndrome and "congenital" arteriovenous fistulae. A clinicopathologic study of a family. , 1965, JAMA.

[48]  A. Daxer,et al.  The fractal geometry of proliferative diabetic retinopathy: implications for the diagnosis and the process of retinal vasculogenesis. , 1993, Current eye research.

[49]  Robert F Spetzler,et al.  Intracranial Aneurysm Surgery in Ehlers-Danlos Syndrome Type IV , 2002, Neurosurgery.

[50]  E. Weibel,et al.  Fractals in Biology and Medicine , 1994 .