Ischemic stroke is a complex multifactorial disorder whose incidence increases as a function of the number of inherited and acquired risk factors. It has been recently suggested that several susceptibility "stroke alleles" act individually, together or in combination with environmental factors in stroke pathogenesis. Patent foramen ovale is considered an independent risk factor for cerebral infarct in young adult with cryptogenic stroke. Paradoxical embolism, from peripheral venous system, embolization from thrombi formed within the atrial septum, and the formation of thrombus as a result of transient atrial arrhythmias, have been advocated as potential pathogenetic mechanisms. Herein is reported a family with cryptogenic strokes probably due to the interaction between prothrombotic genetic polymorphism and atrial septal defects.