[Pathogenesis and genetics of vascular anomalies].
Vascular anomalies, divided into vascular tumors and vascular malformations, are localized defects of angiogenesis. Hemangiomas appear soon after birth, grow quickly, and then spontaneously, but slowly, disappear. In contrast, vascular malformations are congenital defects of vascular development that grow proportionately with the child. Most vascular anomalies are considered non-hereditary. However, due to detailed analysis inherited forms have been observed, which has led to identify mutations in three genes causing familial vascular malformations: in the angiopoietin receptor TIE2 in mucocutaneous venous malformations (VMCM), in glomulin in glomuvenous malformations (GVM) and in RASA1 in the newly recognized phenotype capillary malformation-arteriovenous malformation (CM-AVM). Identification of the causative genes has permitted more precise diagnosis and differential diagnosis, evaluation of phenotypic variability among patients with a proven mutation, study of used treatments in more homogeneous patient groups, and elucidation of the etiopathogenic mechanisms behind vascular malformations. Further studies are needed to unravel the role of genetic variations in the various vascular malformations and to unravel the precise molecular mechanisms that lead to development of these vascular lesions. This should provide development of new-targeted therapies.
Vikkula
M
M
Laboratoire de génétique moléculaire humaine, institut de pathologie cellulaire Christian-de-Duve, université catholique de Louvain, 74, avenue Hippocrate, 1200 Bruxelles, Belgique. vikkula@bchm.ucl.ac.be
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001165:Arteriovenous Malformations / Q000209:etiology / Q000235:genetics; D001808:Blood Vessels / Q000002:abnormalities*; D002196:Capillaries / Q000002:abnormalities; D003937:Diagnosis, Differential; D014644:Genetic Variation / Q000235:genetics; D006391:Hemangioma / Q000209:etiology / Q000235:genetics; D006801:Humans; D042601:Lymphatic Vessels / Q000002:abnormalities; D009154:Mutation / Q000235:genetics; D009383:Neoplasms, Vascular Tissue / Q000209:etiology* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000235:genetics; D010641:Phenotype; D042787:Receptor, TIE-2 / Q000235:genetics; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D020729:p120 GTPase Activating Protein / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; C103024:GLMN protein, human; D020729:p120 GTPase Activating Protein; D042787:Receptor, TIE-2; D022021:Tacrolimus Binding Proteins