ABSTRACT
Patients with both isolated lymphatic malformations and more complex lesions, including capillary-lymphaticovenous malformations (otherwise known as Klippel-Trenaunay syndrome), often have somatic activating mutations in the PI3K-AKT pathway. A similar genetic pathogenesis is operative in related disorders within CLOVES syndrome and other members of the PIK3CA-related overgrowth spectrum (PROS). In addition, mutations in the RAS/MAPK/MEK signaling pathway have been identified in patients with complex vascular presentations that include lymphedema and other lymphatic anomalies. Testing eligibility criteria for somatic PIK3CA mutations have been established. Genetic testing should be strongly considered in these patients.
