Clinical heterogeneity of Pulmonary Arterial Hypertension associated with variants in TBX4.
Por:
Hernandez-Gonzalez I, Tenorio J, Palomino-Doza J, Martinez Meñaca A, Morales Ruiz R, Lago-Docampo M, Valverde Gomez M, Gomez Roman J, Enguita Valls AB, Perez-Olivares C, Valverde D, Gil Carbonell J, Garrido-Lestache Rodríguez-Monte E, Del Cerro MJ, Lapunzina P and Escribano-Subias P
Publicada:
1 ene 2020
Ahead of Print:
29 abr 2020
Resumen:
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.
Filiaciones:
Hernandez-Gonzalez I:
Department of Cardiology, Hospital Universitario Río Hortega, Valladolid, Spain
Tenorio J:
Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institto de Salud Carlos III, Madrid, Spain
Palomino-Doza J:
Department of Cardiology, Inherited Cardiac Disease Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Department of Cardiology, Pulmonary Hypertension Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Centro de Investigación Biomedica en Red en Enfermedades Cardiovasculares, Institto de Salud Carlos III (CIBERCV), Madrid, Spain
Martinez Meñaca A:
Department of Pneumology, Pulmonary Hypertension Unit, Lung Transplant Unit, Hospital Universitario Marqués de Valdecilla, Santander, Spain
Morales Ruiz R:
Department of Radiology, Pulmonary Hypertension Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Lago-Docampo M:
Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain
Valverde Gomez M:
Department of Cardiology, Inherited Cardiac Disease Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Gomez Roman J:
Department of Pathology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
Enguita Valls AB:
Department of Pathology, Pulmonary Hypertension Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Perez-Olivares C:
Department of Cardiology, Pulmonary Hypertension Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Valverde D:
Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain
:
Department of Pneumology, Hospital de Alicante, Alicante, Spain
Garrido-Lestache Rodríguez-Monte E:
Paediatric Cardiology and Grown Up Congenital Heart Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Del Cerro MJ:
Paediatric Cardiology and Grown Up Congenital Heart Disease Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Lapunzina P:
Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institto de Salud Carlos III, Madrid, Spain
Escribano-Subias P:
Department of Cardiology, Pulmonary Hypertension Unit, Hospital Universitario Doce de Octubre, Madrid, Spain
Centro de Investigación Biomedica en Red en Enfermedades Cardiovasculares, Institto de Salud Carlos III (CIBERCV), Madrid, Spain
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