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Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry
Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this w...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499494/ https://www.ncbi.nlm.nih.gov/pubmed/36142358 http://dx.doi.org/10.3390/ijms231810433 |
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author | Cruz-Utrilla, Alejandro Gallego-Zazo, Natalia Tenorio-Castaño, Jair Antonio Guillén, Inmaculada Torrent-Vernetta, Alba Moya-Bonora, Amparo Labrandero, Carlos Rodríguez-Monte, María Elvira Garrido-Lestache Rodríguez-Ogando, Alejandro Rey, María del Mar Rodríguez Vázquez Del Espín, Juana Plata-Izquierdo, Beatriz Álvarez-Fuente, María Moreno-Galdó, Antonio Escribano-Subias, Pilar Marín, María Jesús Del Cerro |
author_facet | Cruz-Utrilla, Alejandro Gallego-Zazo, Natalia Tenorio-Castaño, Jair Antonio Guillén, Inmaculada Torrent-Vernetta, Alba Moya-Bonora, Amparo Labrandero, Carlos Rodríguez-Monte, María Elvira Garrido-Lestache Rodríguez-Ogando, Alejandro Rey, María del Mar Rodríguez Vázquez Del Espín, Juana Plata-Izquierdo, Beatriz Álvarez-Fuente, María Moreno-Galdó, Antonio Escribano-Subias, Pilar Marín, María Jesús Del Cerro |
author_sort | Cruz-Utrilla, Alejandro |
collection | PubMed |
description | Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications. |
format | Online Article Text |
id | pubmed-9499494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94994942022-09-23 Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry Cruz-Utrilla, Alejandro Gallego-Zazo, Natalia Tenorio-Castaño, Jair Antonio Guillén, Inmaculada Torrent-Vernetta, Alba Moya-Bonora, Amparo Labrandero, Carlos Rodríguez-Monte, María Elvira Garrido-Lestache Rodríguez-Ogando, Alejandro Rey, María del Mar Rodríguez Vázquez Del Espín, Juana Plata-Izquierdo, Beatriz Álvarez-Fuente, María Moreno-Galdó, Antonio Escribano-Subias, Pilar Marín, María Jesús Del Cerro Int J Mol Sci Article Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications. MDPI 2022-09-09 /pmc/articles/PMC9499494/ /pubmed/36142358 http://dx.doi.org/10.3390/ijms231810433 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cruz-Utrilla, Alejandro Gallego-Zazo, Natalia Tenorio-Castaño, Jair Antonio Guillén, Inmaculada Torrent-Vernetta, Alba Moya-Bonora, Amparo Labrandero, Carlos Rodríguez-Monte, María Elvira Garrido-Lestache Rodríguez-Ogando, Alejandro Rey, María del Mar Rodríguez Vázquez Del Espín, Juana Plata-Izquierdo, Beatriz Álvarez-Fuente, María Moreno-Galdó, Antonio Escribano-Subias, Pilar Marín, María Jesús Del Cerro Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title | Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title_full | Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title_fullStr | Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title_full_unstemmed | Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title_short | Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry |
title_sort | clinical implications of the genetic background in pediatric pulmonary arterial hypertension: data from the spanish rehiped registry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499494/ https://www.ncbi.nlm.nih.gov/pubmed/36142358 http://dx.doi.org/10.3390/ijms231810433 |
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