Pulmonary Vascular Diseases: Pulmonary Hypertension and HHT—What Are the Roles of Genetic Factors in the Pathogenesis of Pulmonary Vascular Diseases?

  • Toshihiko Sugiura
  • Koichiro Tatsumi
Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)


Heritable pulmonary arterial hypertension (HPAH) and hereditary hemorrhagic telangiectasia (HHT) are rare diseases with autosomal dominant inheritance. HHT is often found to be the underlying cause of pulmonary arteriovenous malformations (PAVMs). Mutations in BMPR2, ACVRLK1, ENG, SMAD9, CAV1, and KCNK3 have been identified in cases of HPAH. Mutations in ACVRLK1, ENG, and SMAD4 have been identified in cases of HHT. The average penetrance of BMPR2 mutations is only 30% in HPAH. In contrast, the average penetrance of ACVRLK1 and ENG mutations is almost 100% in HHT, but the affected organs often differ within the family. It is likely that there are additional genes and genetic/epigenetic or environmental modifiers such as hormones, inflammation, hypoxia, medications/drugs, or infections that play important roles to form phenotypes in HPAH and HHT. Further research is required to fully elucidate these potential mechanisms.


Heritable pulmonary arterial hypertension Hereditary hemorrhagic telangiectasia BMPR2 ACVRLK1 ENG 


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Respirology, Graduate School of MedicineChiba UniversityChibaJapan

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