Heritable pulmonary hypertension: from bench to bedside

Eur Respir Rev. 2017 Sep 6;26(145):170037. doi: 10.1183/16000617.0037-2017. Print 2017 Sep 30.


Mutations in the BMPR2 gene, and more rarely in ACVRL1, endoglin, caveolin-1, KCNK3 and TBX4 genes predispose to heritable pulmonary arterial hypertension, an autosomal dominant disease with incomplete penetrance. Bi-allelic mutations in the EIF2AK4 gene predispose to heritable pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis, an autosomal recessive disease with an unknown penetrance.In France, the national pulmonary hypertension referral centre offers genetic counselling and testing to adults and children. Predictive testing is also proposed to adult relatives at risk of carrying a predisposing mutation. In that context, we offer all asymptomatic BMPR2 mutation carriers a programme to detect pulmonary arterial hypertension at an early phase, as recommended by the 2015 European Society Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines. Finally, pre-implantation genetic diagnosis has been conducted on five embryos from two couples in which the fathers were carriers of a pathogenic BMPR2 mutation.

Publication types

  • Review

MeSH terms

  • Activin Receptors, Type II / genetics
  • Animals
  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Caveolin 1 / genetics
  • DNA Mutational Analysis
  • Endoglin / genetics
  • Familial Primary Pulmonary Hypertension / diagnosis
  • Familial Primary Pulmonary Hypertension / genetics*
  • Familial Primary Pulmonary Hypertension / physiopathology
  • Familial Primary Pulmonary Hypertension / therapy
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Heredity*
  • Humans
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Pedigree
  • Phenotype
  • Potassium Channels, Tandem Pore Domain / genetics
  • Predictive Value of Tests
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Risk Factors
  • T-Box Domain Proteins / genetics
  • Translational Research, Biomedical*


  • CAV1 protein, human
  • Caveolin 1
  • ENG protein, human
  • Endoglin
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • T-Box Domain Proteins
  • TBX4 protein, human
  • potassium channel subfamily K member 3
  • EIF2AK4 protein, human
  • Protein Serine-Threonine Kinases
  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II