Amal Ahmed, Anna M. Brown, Samantha J. Eagle, Evan L. Brittain, Anna R. Hemnes, Rachel T. Sullivan, Eric D. Austin
Meharry Medical College School of Medicine. Vanderbilt University Medical Center and Monroe Carell Jr. Children’s Hospital.
United States
Pulmonary Circulation
Pulm Circ 2026; 16:
DOI: 10.1002/pul2.70375
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal‑dominant vascular disease characterized by telangiectasias and visceral arteriovenous malformations (AVMs), commonly in the lungs, liver, and brain. HHT is linked to mutations in the genes Activin A Receptor Like Type 1 (ACVRL1), Endoglin (ENG), and SMAD Family Member 4 (SMAD4). The ACVRL1 gene encodes the receptor ACVRL1 (Activin A Receptor Like Type 1), also known as ALK1 (Activin Receptor-Like Kinase 1), and belongs to the Transforming Growth Factor-Beta (TGFβ) Superfamily of receptors. Approximately 20% of patients with ACVRL1-associated HHT develop pulmonary arterial hypertension (PAH). [1] In pediatric PAH cohorts, ACVRL1 mutations account for nearly 10% of identified genetic variants. [2] The reduced penetrance of PAH among ACVRL1 mutation carriers suggests that additional modifiers account for PAH development. [3]. Given the relevance of the bone‑morphogenetic‑protein (BMP) pathway to the pathogenesis of PAH, and the intimate relationship of TGFβ superfamily signaling partners including ACVRL1 and BMPR2, genes which modify BMP-TGFβ signaling balance may contribute to PAH development in children with ACVRL1‑positive HHT. One such gene is SMAD9 (Receptor Regulated SMAD 9); the protein product of SMAD 9 (SMAD8) which mediates downstream TGFβ signaling. Herein, we report what we believe to be the youngest reported case of PAH in ACVRL1‑mediated HHT, in a patient who co‑harbors a SMAD9 mutation.
Category
Class I. Heritable Pulmonary Hypertension
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes