SOX17 variants are associated with severe pulmonary arterial hypertension with and without congenital heart disease
Abstract
BACKGROUND: SOX17 has recently been identified as a risk gene for idiopathic, heritable and co-incidental congenital heart disease (CHD) pulmonary arterial hypertension (PAH). Distinct phenotypic characteristics in PAH associated with variants in SOX17 (SOX17-PAH) are still emerging.
METHODS: Retrospective review describing natural history and outcomes in a national cohort of children with SOX17-PAH. Findings were collated with data from previously reported individuals to compare adult and paediatric cases.
RESULTS: In the current cohort 8/69 (11.6 %) children tested had a variant and 6 variants are newly reported. Six children had CHD. Haemodynamic assessment demonstrated high mean pulmonary artery pressure (60 [49-102] mmHg) and pulmonary vascular resistance (17.2 [9.6-27.7] WU.m). Atypical radiological features included ground-glass opacification and pulmonary arterial tortuosity. Despite combination-therapy, outcomes were poor (lung transplant/death = 5) with median transplant/Potts-shunt-free survival of 7.5 [0.1-15.1] years. In addition to the present cohort, published phenotypic data were available in 71 individuals. Combining data across studies showed a bimodal distribution of age at disease onset, with majority having childhood-onset PAH (69 %). Those with CHD were diagnosed younger (8.8 versus 21.7 years, p < 0.001). Variants located in the HMG-box domain were more likely to have childhood-onset PAH (52.6 % versus 20.7 %, p = 0.005). Where reported, 26 % of paediatric cases underwent Potts-shunt and 38 % of all cases underwent lung transplantation.
CONCLUSION: This study suggests SOX17-PAH is characterised by unfavourable haemodynamics, high rates of CHD, and treatment-refractory disease. The location of SOX17 variants may influence the age of onset of PAH.
Date
2025-12-23
Type
Article
Subject
Children
Collections
Citation
Hyder Y, Irving R, Ramalingam S, Wakerley BR. Assessment and management of pulsatile tinnitus. Pract Neurol. 2025 Dec 24:pn-2025-004624. doi: 10.1136/pn-2025-004624. Epub ahead of print.
Journal / Source Title
International journal of cardiology
DOI
10.1016/j.ijcard.2025.134114
PMID
41448277
Publisher
BMJ Pub. Group