Marc Humbert, MD, PhD, FERS
Université Paris-Saclay, Le Kremlin-Bicêtre, France

Pulmonary arterial hypertension (PAH) is a rare and severe condition which can be idiopathic, familial, induced by drugs or toxins, or associated with other conditions such as connective tissue disease or congenital heart disease. Heterozygous BMPR2 mutation is the most common genetic cause of familial/heritable PAH. BMPR2 encodes a type II receptor of the transforming growth factor beta superfamily. BMPR2 mutation carriers have a lifetime risk of developing PAH of ~20%, with penetrance higher in female carriers (42%) compared with male (14%). Genetic counselling allows detection of mutations in PAH predisposing genes in patients with idiopathic, familial or drug-induced PAH. Relatives of patients carrying BMPR2 mutation can also be counselled and tested. In asymptomatic BMPR2 mutation carriers, screening can identify early-stage PAH. Other gene mutations have been identified in PAH (ACVRL1, EIF2AK4, TBX4, SOX17…). This presentation will genotype phenotype relationships in heritable PAH.

Learning Objectives
At the end of this presentation, attendees will be able to:

  • Describe the main gene mutations causing heritable pulmonary hypertension with an emphasis on BMPR2 and EIF2AK4;
  • Discuss the results of a PAH screening program in asymptomatic carriers of BMPR2 mutations; and
  • Present recent findings on rare mutations linking heritable PAH with lung development.