With the identification of the PI3K/AKT/mTOR pathway as an important driver of somatic overgrowth syndromes (84) and the identification of somatic PI3K mutations within certain vascular malformations (41, 85, 86), PI3K inhibition has become the next major therapeutic target for vascular anomalies (87–89). This evidence concerns the gene PIK3CA and overgrowth syndrome.