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

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.

Keywords: Chest CT; Heritable PAH; Pediatric PAH; Pulmonary arterial hypertension; TBX4.