Hemodynamic and Genetic Analysis in Children With Idiopathic, Heritable, and Congenital Heart Disease Associated Pulmonary Arterial Hypertension

Respir Res. 2013 Jan 9;14(1):3. doi: 10.1186/1465-9921-14-3.


Background: Aim of this prospective study was to compare clinical and genetic findings in children with idiopathic or heritable pulmonary arterial hypertension (I/HPAH) with children affected with congenital heart defects associated PAH (CHD-APAH).

Methods: Prospectively included were 40 consecutive children with invasively diagnosed I/HPAH or CHD-APAH and 117 relatives. Assessment of family members, pedigree analysis and systematic screening for mutations in TGFß genes were performed.

Results: Five mutations in the bone morphogenetic protein type II receptor (BMPR2) gene, 2 Activin A receptor type II-like kinase-1 (ACVRL1) mutations and one Endoglin (ENG) mutation were found in the 29 I/HPAH children. Two mutations in BMPR2 and one mutation in ACVRL1 and ENG, respectively, are described for the first time. In the 11 children with CHD-APAH one BMPR2 gene mutation and one Endoglin gene mutation were found. Clinical assessment of relatives revealed familial aggregation of the disease in 6 children with PAH (HPAH) and one CHD-APAH patient. Patients with mutations had a significantly lower PVR.

Conclusion: Mutations in different TGFß genes occurred in 8/29 (27.6%) I/HPAH patients and in 2/11 (18.2%) CHD-APAH patients and may influence the clinical status of the disease. Therefore, genetic analysis in children with PAH, especially in those with I/HPAH, may be of clinical relevance and shows the complexity of the genetic background.

Publication types

  • Comparative Study

MeSH terms

  • Activin Receptors, Type II / genetics
  • Adolescent
  • Antigens, CD / genetics
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Endoglin
  • Familial Primary Pulmonary Hypertension
  • Female
  • Genetic Predisposition to Disease
  • Heart Defects, Congenital / complications
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology*
  • Hemodynamics / genetics*
  • Heredity
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / physiopathology*
  • Infant
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Prospective Studies
  • Receptors, Cell Surface / genetics


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II