The following is a summary of “An emerging phenotype of pulmonary arterial hypertension patients carrying SOX17 variants” published in the December 2022 issue of Respiratory by Montani et al.

Patients with pulmonary arterial hypertension (PAH) who carry somatic mutations in SOX17 have an elusive phenotype. Using data from the French Pulmonary Hypertension Network, researchers describe the demographics, clinical presentation, and outcomes of individuals with heritable PAH who contain SOX17 mutations. There were a total of 20 cases, and 8 healthy relatives were found. 

The female-to-male diagnosis ratio was 1.5, and the median (range) age at diagnosis was 17 (2-53) years. Most patients were severely hemodynamically compromised at the time of diagnosis, with 74% being in New York Heart Association Functional Class III or IV, and the median pulmonary vascular resistance being 14.0 (4.2-31.5) WU. About 7 PAH patients (or 35% of the total) were found to have congenital heart disease(CHD). Compared to individuals with PAH who did not have CHD, those whose PAH was caused by CHD were diagnosed much earlier. Haemoptysis returned in 4 patients, or 20%, necessitating additional arterial embolization. Dilated, convoluted pulmonary vasculature, ground-glass opacities, and bronchial and nonbronchial artery anomalies were seen on chest computed tomography in 13 of 16 patients (81%).

About 10 patients underwent lung transplantation, and one received a heart-lung transplant because of concomitant CHD after a median (range) follow-up of 47 (1-591) months. Lung explants revealed congestion, significant pulmonary arterial remodelling, dilated subpleural vessels, and many hemorrhagic foci upon histopathological examination. The severe phenotype of PAH caused by SOX17 pathogenic mutations is often accompanied by congestive heart failure, hemoptysis, and radiological abnormalities. In addition, pathological examination indicates significant abnormalities of the pulmonary arteries and the systemic arteries of the chest.