Pediatric pulmonary veno-occlusive disease associated with a novel BMPR2 variant

Area of Science:

• Cardiovascular Sciences
• Genetics
• Pediatric Pulmonology

Background:

• Pulmonary veno-occlusive disease (PVOD) and idiopathic/heritable pulmonary arterial hypertension (I/HPAH) are severe forms of pulmonary hypertension (PH) with distinct genetic underpinnings.
• A pediatric case of severe PH, initially refractory to treatment and presenting with hypoxemia and ground-glass opacities, was diagnosed as PVOD.

Discussion:

• The patient developed pulmonary edema following prostaglandin I2 administration, a known complication in PVOD.
• Pathological examination of the explanted lung revealed characteristic PVOD findings: intimal thickening and luminal narrowing of pulmonary veins.
• Genetic analysis identified a novel BMPR2 splice acceptor variant (c.77-2A>C), a mutation typically associated with I/HPAH.

Key Insights:

• This case represents the first pediatric instance of PVOD associated with a BMPR2 variant.
• The findings challenge the strict classification of PVOD and I/HPAH, suggesting they exist on a continuum of pulmonary vascular disease.
• The BMPR2 gene, implicated in I/HPAH, may also play a role in the pathogenesis of PVOD.

Outlook:

• Further research into the genetic landscape of PVOD is warranted to understand the role of BMPR2 and other genes.
• This case underscores the importance of genetic testing in diagnosing complex pediatric PH cases.
• Expanding the understanding of the PVOD and I/HPAH spectrum may lead to improved diagnostic strategies and targeted therapies for pediatric PH.