Katharina Schimmel, Tucker Hallmark, Evon DeBose-Scarlett, Yue Qi, Serena Tan, Domenico Mastrodicasa, Rachel K. Hopper, Joseph Wu, Douglas Marchuk, Edda Spiekerkoetter
University of Arizona College of Medicine-Phoenix and Phoenix Children’s Hospital. Duke University School of Medicine.
Stanford University School of Medicine and Lucile Packard Children’s Hospital. University of Washington School of Medicine.
United States
Journal of the American College of Cardiology Case Reports
JACC Case Rep 2026; 31:
DOI: 10.1016/j.jaccas.2025.106786
Abstract
Background: Hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH) are rare vascular diseases whose pathobiology is poorly understood. HHT is characterized by arteriovenous malformations, whereas PAH by an occlusive pulmonary vasculopathy that includes plexiform lesions.
Case summary: A female patient with PAH and HHT developed right heart failure with severe hypoxemia despite years of medical treatment for PAH, necessitating a heart-lung transplantation.
Discussion: Histological and molecular analysis of the lung explant revealed that, in addition to the inherited HHT-causing variant in the endoglin gene, a plexiform lesion harbored an oncogenic, somatic phosphoinositide-3-kinase, PIK3CA activating mutation, which in this case may have driven endothelial cell proliferation.
Take-home messages: This novel discovery sheds light on the molecular basis of plexiform lesion development in this rare case of combined PAH and HHT, highlighting a potential role of somatic mutations in driving endothelial cell proliferation in plexiform lesions.
Category
Class I. Heritable Pulmonary Hypertension
Pulmonary Arteriovenous Malformations
Genetic Factors Associated with Pulmonary Vascular Disease
Pulmonary Vascular Pathology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes