Novel Combinatorial Factors in the WNT Pathway in a Pediatric Case of Valvular Aortic Stenosis from Lebanon: A Brief Report

Wiam Ataya¹Fathima Mohammed²Mariam Toufic Arabi³Fadi Bitar³Georges Michel Nemer^2,4*

• ¹Beirut Arab University, Beirut, Lebanon
• ²College of Health & Life Science, Hamad Bin Khalifa University, Doha, Qatar
• ³Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
• ⁴Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

Aortic stenosis (AS) is one of the most common valvular diseases, with a largely undiscovered complex genetic background and multiple genes at play particularly in consanguineous populations, where familial clustering would support a strong hereditary component of the disease. This study aims to uncover the genetic basis of AS in a consanguineous Lebanese family using whole-exome sequencing (WES) with the purpose of identifying potential pathogenic variants. We report the case of a 12-year-old female (the only child of consanguineous parents) with valvular AS that underwent multiple surgical interventions, including balloon valvuloplasty, Ross procedure, and right ventricle-pulmonary artery (RV-PA) conduit replacement. Echocardiography revealed dilated aortic root and ascending aorta, mild-moderate tricuspid regurgitation, severe aortic stenosis, and a bicuspid aortic valve , she was analyzed along with her phenotypically normal parents using WES, which revealed the presence of three heterozygous variants in genes of the Wnt signaling pathway: APCDD1 , DVL1, and AXIN2 .This study underlines the importance of the Wnt pathway in AS especially amongst consanguineous families.