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Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation
- Source :
- European Respiratory Journal, European Respiratory Journal, European Respiratory Society, 2020, 55 (5), pp.1902340. ⟨10.1183/13993003.02340-2019⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- IntroductionTBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
medicine.medical_specialty
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Hemodynamics
medicine.disease_cause
Gastroenterology
Vascular remodelling in the embryo
03 medical and health sciences
0302 clinical medicine
Diffusing capacity
Internal medicine
Parenchyma
medicine
Lung transplantation
Mutation
business.industry
Phenotype
3. Good health
030104 developmental biology
medicine.anatomical_structure
030228 respiratory system
Vascular resistance
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 09031936 and 13993003
- Database :
- OpenAIRE
- Journal :
- European Respiratory Journal, European Respiratory Journal, European Respiratory Society, 2020, 55 (5), pp.1902340. ⟨10.1183/13993003.02340-2019⟩
- Accession number :
- edsair.doi.dedup.....f84fb335c15f375a930f25e824b0ad13