Alejandro Cruz-Utrilla1, Natalia Gallego-Zazo, Jair Antonio Tenorio-Castaño, Inmaculada Guillén, Alba Torrent-Vernetta, Amparo Moya-Bonora, Carlos Labrandero, María Elvira Garrido-Lestache Rodríguez-Monte, Alejandro Rodríguez-Ogando, María del Mar Rodríguez Vázquez Del Rey, Juana Espín, Beatriz Plata-Izquierdo, María Álvarez-Fuente, Antonio Moreno-Galdó, Pilar Escribano-Subias, María Jesús Del Cerro Marín
Hospital Universitario 12 de Octubre. Hospital Universitario La Paz. Instituto de Salud Carlos III. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability. Hospital Universitario Virgen del Rocío. Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus and Universitat Autònoma de Barcelona. Hospital Universitari i Politècnic La Fe. Ramón y Cajal University Hospital. Hospital Universitario Gregorio Marañón. Hospital Universitario Virgen de las Nieves. Hospital Universitario Virgen de la Arrixaca. Hospital Universitario de Salamanca and Universidad de Salamanca. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares.
Spain and Belgium
International Journal of Molecular Sciences
Int J Mol Sci 2022; 23:
DOI: 10.3390/ijms231810433
Abstract
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.
Category
Class I. Idiopathic Pulmonary Hypertension
Class I. Heritable Pulmonary Hypertension
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Class I. Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
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Free PDF File or Full Text Article Available Through PubMed or DOI: Yes