Pulmonary vascular phenotype identified in patients with () or variants: an international multicentre study.

BACKGROUND

Bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), encoded by and , respectively, play a pivotal role in pulmonary vascular regulation. variants have been reported in pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT). However, the phenotype of and carriers remains largely unexplored.

METHODS

We report the characteristics and outcomes of PAH patients in and carriers from the French and Dutch pulmonary hypertension registries. A literature review explored the phenotypic spectrum of these patients.

RESULTS

26 PAH patients were identified: 20 harbouring heterozygous variants, one homozygous variant, four heterozygous variants, and one with both and variants. The prevalence of and variants was 1.3% and 0.4%, respectively. Median age at PAH diagnosis was 30 years, with a female/male ratio of 1.9. Congenital heart disease (CHD) was present in 15.4% of the patients. At diagnosis, most of the patients (61.5%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise (median (range) pulmonary vascular resistance 9.0 (3.3-40.6) WU). Haemoptysis was reported in four patients; none met the HHT criteria. Two patients carrying variants underwent lung transplantation, revealing typical PAH histopathology. The literature analysis showed that 7.6% of carriers developed isolated HHT, and identified cardiomyopathy and developmental disorders in carriers.

CONCLUSIONS

and pathogenic variants are rare among PAH patients, and occasionally associated with CHD. HHT cases among carriers are limited according to the literature. full phenotypic ramifications warrant further investigation.