Julien Grynblat, Florence Coulet, Thomas Lacoste-Palasset, Xavier Jais, Eric Austin, Dunbar Ivy, Maria-Rosa Ghigna, Antoine Beauvais, Etienne-Marie Jutant, Athénaïs Boucly, Mathilde Meot, Sophie-Guiti Malekzadeh-Milani, Marilyn Levy
Université Paris-Saclay and Hôpital Bicêtre. Hôpital Necker-Enfants malades and AP-HP, Université Paris Cité. Sorbonne Université, Assistance Publique-Hôpitaux de Paris and Hôpital Pitié-Salpêtrière. Vanderbilt University Medical Center and Monroe Carell Jr. Children’s Hospital. University of Colorado Denver Anschutz Medical Center and Children’s Hospital Colorado. Gustave Roussy Cancer Campus.
France and United States
European Respiratory Journal
Eur Respir J 2026;
DOI: 10.1183/13993003.00808-2026
Abstract
Pulmonary hypertension (PH) may complicate a broad range of genetic syndromes beyond the established spectrum of heritable pulmonary arterial hypertension. Although these conditions are individually rare, together they represent an emerging field at the crossroads of developmental biology, vascular medicine, and precision genomics. In many cases, PH may be the presenting feature or may remain unrecognized because it occurs within complex multisystem disorders involving congenital heart disease, developmental lung abnormalities, parenchymal lung disease, vascular malformations, or extra-pulmonary manifestations. Recent advances in human genetics have expanded the spectrum of genes and syndromes associated with PH, including disorders involving altered lung and vascular development, dysregulated hypoxia signaling, smooth muscle dysfunction, chromosomal abnormalities, and syndromic vasculopathies. In this review, we summarize the main genetic syndromes associated with PH and discuss their underlying mechanisms, clinical phenotypes, diagnostic clues, and therapeutic implications. We paid particular attention to conditions that illustrate the marked heterogeneity of syndromic PH such as FLNA-related disorders, neurofibromatosis type 1, Noonan syndrome, Down syndrome, Alagille syndrome, Cantú syndrome, Chuvash polycythaemia, cobalamin C deficiency, multisystemic smooth muscle dysfunction syndrome, alveolar capillary dysplasia with misalignment of pulmonary veins, and Moya Moya syndrome.
Category
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult 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: No