Pathogenesis of vascular anomalies

Vascular anomalies are localized defects of vascular development. Most of them occur sporadically (ie, there is no familial history of lesions, yet in a few cases clear inheritance is observed). These inherited forms are often characterized by multifocal lesions that are mainly small in size and increase in number with patients' age. The authors review the known (genetic) causes of vascular anomalies and call attention to the concept of Knudson's double-hit mechanism to explain incomplete penetrance and large clinical variation in expressivity observed in inherited vascular anomalies. The authors also discuss the identified pathophysiological pathways involved in vascular anomalies and how it has opened the doors toward a more refined classification of vascular anomalies and the development of animal models that can be tested for specific molecular therapies.