Pathogenic variants in<i>PIK3CA</i>are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly
Jeremy Grenier, Alexandra J. Borst, Sarah E. Sheppard, Kristen Snyder, Dong Li, Lea F. Surrey, Alyaa Al‐Ibraheemi, David R. Weber, James R. Treat, Christopher L. Smith, Pablo Laje, Yoav Dori, Denise M. Adams, Michael R. Acord, Abhay Srinivasan
Abstract
Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.