title: Genetic testing and blood biomarkers in paediatric pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.
abstract: Childhood-onset pulmonary arterial hypertension (PAH) is considered complex and multifactorial, with relatively poor estimates of the natural history of the disease. Strategies allowing earlier detection, establishment of disease aetiology together with more accurate and sensitive biomarkers could enable better estimates of prognosis and individualise therapeutic strategies. Evidence is accumulating that genetic defects play an important role in the pathogenesis of idiopathic and hereditary forms of PAH. Altogether nine genes have been reported so far to be associated with childhood onset PAH suggesting that comprehensive multigene diagnostics can be useful in the assessment. Identification of disease-causing mutations allows estimates of prognosis and forms the most effective way for risk stratification in the family. In addition to genetic determinants the analysis of blood biomarkers are increasingly used in clinical practice to evaluate disease severity and treatment responses. As in genetic diagnostics, a multiplex approach can be helpful, as a single biomarker for PAH is unlikely to meet all requirements. This consensus statement reviews the current evidence for the use of genetic diagnostics and use of blood biomarkers in the assessment of paediatric patients with PAH.
authors.affiliation: Department of Paediatric Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pattathu
authors.affiliation: Department of Paediatric Cardiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gorenflo
authors.affiliation: Perinatal Center Grosshadern, Dr. von Haunersches Children`s Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hilgendorff
authors.affiliation: Department of Clinical Physiolology, University Hospital Helsinki, University of Helsinki, Helsinki, Finland Blueprint Genetics, Biomedicum Helsinki, Helsinki, Finland.
authors.forename: Juha W
authors.initials: JW
authors.lastname: Koskenvuo
authors.affiliation: Paediatric Heart Centre, University Hopsital of Giessen and Marburg, Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Apitz
authors.affiliation: Department of Paediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hansmann
authors.affiliation: Blueprint Genetics, Biomedicum Helsinki, Helsinki, Finland Department of Paediatric Cardiology, Childrens Hospital Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Tero-Pekka
authors.initials: TP
authors.lastname: Alastalo
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics; D002648:Child; D032921:Consensus; D019468:Disease Management; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology; D016232:Endothelins / Q000097:blood; D065627:Familial Primary Pulmonary Hypertension / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D037502:Galectin 3 / Q000097:blood; D005820:Genetic Testing; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009419:Nerve Tissue Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D051904:Smad8 Protein / Q000235:genetics; D020107:Troponin T / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C495540:CAV1 protein, human; D051242:Caveolin 1; C064206:ENG protein, human; D000071063:Endoglin; D016232:Endothelins; C526140:GDF15 protein, human; D037502:Galectin 3; D055436:Growth Differentiation Factor 15; C499374:NOTCH3 protein, human; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D024683:Potassium Channels, Tandem Pore Domain; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C107514:SMAD9 protein, human; D051904:Smad8 Protein; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C420132:potassium channel subfamily K member 3; D014527:Uric Acid; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein; C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D052004:Bone Morphogenetic Protein Receptors