Ignacio Hernandez-Gonzalez, Jair Tenorio, Julian Palomino-Doza, Amaya Martinez Meñaca, Rafael Morales Ruiz, Mauro Lago-Docampo, Marı´a Valverde Gomez, Javier Gomez Roman, Ana Bele´n Enguita Valls, Carmen Perez-Olivares, Diana Valverde, Joan Gil Carbonell, Elvira Garrido-Lestache Rodrı´guez-Monte, Maria Jesus del Cerro, Pablo Lapunzina, Pilar Escribano-Subias
Hospital Universitario Río Hortega. Hospital Universitario La Paz. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and Institto de Salud Carlos III. Hospital Universitario Doce de Octubre. Hospital Universitario Marqués de Valdecilla. University of Vigo. Hospital de Alicante. Hospital Universitario Ramón y Cajal.
Spain
Public Library of Science One
PLOS One 2020; 15:
DOI: 10.1371/journal.pone.0232216
Abstract
Background: The knowledge of hereditary predisposition has changed our understanding of Pulmonary Arterial Hypertension. Genetic testing has been widely extended and the application of Pulmonary Arterial Hypertension specific gene panels has allowed its inclusion in the diagnostic workup and increase the diagnostic ratio compared to the traditional sequencing techniques. This is particularly important in the differential diagnosis between Pulmonary Arterial Hypertension and Pulmonary Venoocclusive Disease.
Methods: Since November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of Pulmonary Arterial Hypertension or Pulmonary Venoocclusive Disease included in the Spanish Registry of Pulmonary Arterial Hypertension. Herein, we present the clinical phenotype and prognosis of all Pulmonary Arterial Hypertension patients with disease-associated variants in TBX4.
Results: Out of 579 adults and 45 children, we found in eight patients from seven families, disease-causing associated variants in TBX4. All adult patients had a moderate-severe reduction in diffusion capacity. However, we observed a wide spectrum of clinical presentations, including Pulmonary Venoocclusive Disease suspicion, interstitial lung disease, pulmonary vascular abnormalities and congenital heart disease.
Conclusions: Genetic testing is now essential for a correct diagnosis work-up in Pulmonary Arterial Hypertension. TBX4-associated Pulmonary Arterial Hypertension has marked clinical heterogeneity. In this regard, a genetic study is extremely useful to obtain an accurate diagnosis and provide appropriate management.
Category
Genetic Factors Associated with Pulmonary Vascular Disease
Class I. Idiopathic Pulmonary Hypertension
Class I. Heritable Pulmonary Hypertension
Class I. Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis
Symptoms and Findings Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes