Numerous pathophysiogenetic mechanisms have been suggested such as venous dysplasia of the emissary veins in the intracranial circulation, neural crest alterations leading to alterations of autonomic perivascular nerves, mutation of the GNAO gene in the Sturge-Weber syndrome, PIK3CA mutation in malformative/overgrowth syndromes such as the Klippel-Trenaunay syndrome, and the twin-spotting phenomenon in phakomatosis pigmentovascularis. Here, PIK3CA is linked to Klippel-Trénaunay syndrome.