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Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children

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Abstract

Background

Mutations in the T-Box 4 (TBX4) gene are a lesser-known cause of heritable pulmonary arterial hypertension (PAH). Patients with heritable PAH typically have worse outcomes when compared with patients with idiopathic PAH, yet little is known about the phenotypical presentation of this mutation.

Objective

This article reviews the pattern of chest CT findings in pediatric patients with PAH and TBX4 mutations and compares their radiographic presentation with those of age-matched patients with PAH but without TBX4 mutations.

Materials and methods

A retrospective chart review of the pulmonary arterial hypertension database was performed. Pediatric patients with PAH-confirmed TBX4 mutations and an available high CT were included. Fifteen (9 females) patients met the inclusion criteria. Fourteen (8 females) age-matched controls with diagnosed PAH but without TBX4 mutations were also evaluated. The median age at diagnosis was 7.4 years (range: 0.1–16.4 years). Demographic information and clinical outcomes were collected. CTs of the chest were reviewed for multiple airway, parenchymal, and structural abnormalities (16 imaging findings in total). Chi-square tests were used to compare the prevalence of each imaging finding in the TBX4 cohort compared to the control group.

Results

Patients with TBX-4 mutations had increased presence of peripheral or subpleural irregularity (73% vs 0%, P < 0.01), cystic lucencies (67% vs 7%, P < 0.01), and linear or reticular opacity (53% vs 0%, P < 0.01) compared to the control group. Ground glass opacities, bronchiectasis, and centrilobular nodules were not significantly different between the two patient groups (P > 0.05).

Conclusion

TBX4 mutations have distinct imaging phenotypes in pediatric patients with PAH. Compared to patients without this mutation, patients with TBX-4 genes typically present with peripheral or subpleural irregularity, cystic lucencies, and linear or reticular opacity.

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Data availability

The data supporting the findings of this research are available as supplemental materials accompanying this article.

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Authors and Affiliations

  1. Department of Radiology, Children’s Hospital Colorado, Aurora, CO, USA

    Helio V. Neves da Silva, Jason P. Weinman, Erin K. Englund & Lorna P. Browne

  2. University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA

    Helio V. Neves da Silva, Jason P. Weinman, Robin R. Deterding, Dunbar D. Ivy & Lorna P. Browne

  3. Department of Internal Medicine, Alameda Health System, Highland Hospital, Oakland, CA, USA

    Helio V. Neves da Silva

  4. The Breathing Institute, Children’s Hospital Colorado, Aurora, CO, USA

    Robin R. Deterding

  5. The Heart Institute, Children’s Hospital Colorado, Aurora, CO, USA

    Dunbar D. Ivy

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  1. Helio V. Neves da Silva
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  2. Jason P. Weinman
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  3. Erin K. Englund
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  6. Lorna P. Browne
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All authors contributed to the study’s conception and design. All authors read and approved the final manuscript.

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Correspondence to Helio V. Neves da Silva.

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This study was approved by the Colorado Multiple Institutional Review Board (COMIRB).

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Neves da Silva, H.V., Weinman, J.P., Englund, E.K. et al. Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children. Pediatr Radiol 54, 199–207 (2024). https://doi.org/10.1007/s00247-023-05848-7

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  • DOI: https://doi.org/10.1007/s00247-023-05848-7

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