Abstract
Background
Germline mutation in bone morphogenetic protein type II (BMPR2) is the most common cause of idiopathic/heritable pulmonary hypertension in pediatric patients. Despite the discovery of this gene there are no known descriptions of the CT or CT angiography findings in these children.
Objective
To correlate the clinical presentation, pathology and chest CT findings in pediatric patients with pulmonary hypertension caused by mutations in the BMPR2 gene.
Materials and methods
We performed a search to identify pediatric patients with a BMPR2 mutation and CT or CT angiography with the clinical history of pulmonary hypertension. Three pediatric radiologists reviewed the children’s CT imaging findings and ranked the dominant findings in order of prevalence via consensus.
Results
We identified three children with pulmonary hypertension and confirmed germline BMPR2 mutations, two of whom had undergone lung biopsy. We then correlated the imaging findings with histopathology and clinical course.
Conclusion
All of our patients with BMPR2 mutations demonstrated a distinct CT pattern of ground-glass nodules with a prominent central enhancing vessel/nodule. These findings correlated well with the pathological findings of plexogenic arteriopathy.
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References
Berger RMF, Beghetti M, Humpl T et al (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379:537–546
Runo JR, Loyd JE (2003) Primary pulmonary hypertension. Lancet 361:1533–1544
Lane KB, Machado RD, Pauciulo MW et al (2000) Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26:81–84
Evans JDW, Girerd B, Montani D et al (2016) BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med 4:129–137
Heldin CH, Miyazono K, Ten Dijke P (1997) TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465–471
Morrell NW (2006) Pulmonary hypertension due to BMPR2 mutation: a new paradigm for tissue remodeling? Proc Am Thorac Soc 3:680–686
Croix CMS, Steinhorn RH (2016) New thoughts about the origin of plexiform lesions. Am J Respir Crit Care Med 193:484–485
Grosse C, Grosse A (2010) CT findings in diseases associated with pulmonary hypertension: a current review. Radiographics 30:1753–1777
Compton GL, Florence J, MacDonald C et al (2015) Main pulmonary artery–to–ascending aorta diameter ratio in healthy children on MDCT. AJR Am J Roentgenol 205:1322–1325
Brody AS, Guillerman RP, Hay TC et al (2010) Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT. AJR Am J Roentgenol 194:238–244
Weinman JP, Manning DA, Liptzin DR et al (2017) HRCT findings of childhood follicular bronchiolitis. Pediatr Radiol 47:1759–1765
Weinman JP, White CJ, Liptzin DR et al (2018) High-resolution CT findings of pulmonary interstitial glycogenosis. Pediatr Radiol 48:1066–1072
LeMoine BD, Browne LP, Liptzin DR et al (2019) High-resolution computed tomography findings of thyroid transcription factor 1 deficiency (NKX2–1 mutations). Pediatr Radiol 49:869–875
Galambos C, Sims-Lucas S, Abman SH, Cool CD (2016) Intrapulmonary bronchopulmonary anastomoses and plexiform lesions in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 193:574–576
Townsley MI (2013) Structure and composition of pulmonary arteries, capillaries and veins. Compr Physiol 2:675–709
Oshima K, Crockett ES, Joshi SR et al (2019) Aneurysm-type plexiform lesions form in supernumerary arteries in pulmonary arterial hypertension: potential therapeutic implications. Am J Physiol Lung Cell Mol Physiol 317:L805–L815
Westöö C, Norvik C, Peruzzi N et al (2021) Distinct types of plexiform lesions identified by synchrotron-based phase contrast micro-CT. Am J Physiol Cell Mol Physiol 321:L17–L28
Rodríguez-Roisin R, Krowka MJ, Hervé P, Fallon MB (2004) Pulmonary-hepatic vascular disorders (PHD). Eur Respir J 24:861–880
Aldenkortt F, Aldenkortt M, Caviezel L et al (2014) Portopulmonary hypertension and hepatopulmonary syndrome. World J Gastroenterol 20:8072–8081
Ghigna MR, Guignabert C, Montani D et al (2016) BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension. Eur Respir J 48:1668–1681
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Dr. Weinman is a reviewer of imaging studies in fibrosing lung disease for Parexel/Calyx and is on the advisory board and receives non-financial support from Boehringer Ingelheim for fibrosing lung disease. The University of Colorado School of Medicine has received consulting fees for Dr. Ivy from Actelion, Bayer, Gilead, Eli Lilly, Pfizer and United Therapeutics. Dr. Deterding is chief executive officer and founder of NowVitals Inc., founder and chief medical officer of Earables, coordinating investigator and consultant for Boehringer Ingelheim, and founder and consultant for EvoEndo. The other authors have nothing to disclose.
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Weinman, J.P., Mong, D.A., Malone, L.J. et al. Chest computed tomography findings of ground-glass nodules with enhancing central vessel/nodule in pediatric patients with BMPR2 mutations and plexogenic arteriopathy. Pediatr Radiol 52, 2549–2556 (2022). https://doi.org/10.1007/s00247-022-05413-8
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DOI: https://doi.org/10.1007/s00247-022-05413-8