Genetics of pulmonary hypertension in the clinic

Curr Opin Pulm Med. 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414.


Purpose of review: Heritable pulmonary arterial hypertension (PAH) is an autosomal dominant disease with incomplete penetrance because of mutations in bone morphogenetic protein receptor-II (BMPR2), activin A receptor type II-like kinase 1, endoglin, caveolin-1, potassium channel subfamily K, member 3, and T-box gene 4 genes. Heritable pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH) is an autosomal recessive disease because of biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene. The 2015 european society of cardiology (ESC) and european respiratory society (ERS) pulmonary hypertension guidelines recommend genetic counselling and testing to adults and children with PAH or PVOD/PCH as well as in adult relatives at risk of carrying a predisposing mutation.

Recent findings: In France, genetic counseling and testing are offered to all patients displaying sporadic or familial form of PAH or PVOD/PCH and to their relatives at high risk of carrying a predisposing mutation. Patients with a heritable form of PAH are younger at diagnosis with a worse hemodynamic and a dismal prognosis. Patients with a heritable form of PVOD/PCH are younger at diagnosis with a worse response to specific PAH therapies. A program to detect PAH in an early phase was offered to all asymptomatic BMPR2 mutation carriers, according to the 2015 ESC/ERS guidelines. Finally, preimplantation genetic diagnosis has been performed in families with a history of BMPR2 mutations.

Summary: Genetic counseling and testing has to be implemented in pulmonary hypertension centers.

Publication types

  • Review

MeSH terms

  • Bone Morphogenetic Protein Receptors, Type II / genetics*
  • Caveolin 1 / genetics
  • Europe
  • Familial Primary Pulmonary Hypertension* / diagnosis
  • Familial Primary Pulmonary Hypertension* / genetics
  • Genetic Counseling* / methods
  • Genetic Counseling* / organization & administration
  • Genetic Testing / methods
  • Hemangioma, Capillary* / diagnosis
  • Hemangioma, Capillary* / genetics
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / genetics
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Mutation
  • Practice Guidelines as Topic
  • Protein Serine-Threonine Kinases / genetics
  • Pulmonary Veno-Occlusive Disease* / diagnosis
  • Pulmonary Veno-Occlusive Disease* / genetics
  • Risk Assessment / methods


  • CAV1 protein, human
  • Caveolin 1
  • EIF2AK4 protein, human
  • Protein Serine-Threonine Kinases
  • Bone Morphogenetic Protein Receptors, Type II

Supplementary concepts

  • Hemangiomatosis, familial pulmonary capillary