Type B Aortic Dissection Following Abdominal Aortic Aneurysm Repair in Loeys-Dietz Syndrome: A Novel TGFBR1 Variant

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by aggressive aortic pathology, primarily caused by pathogenic variants in genes such as TGFBR1. We report a 44-year-old female with a known LDS diagnosis who presented with a symptomatic, rapidly expanding abdominal aortic aneurysm (44.8 mm) with concurrent iliac and renal artery involvement. Given the high rupture risk, she underwent open abdominal aortic reconstruction. However, she subsequently developed a Type B aortic dissection nearly 2 months after the initial repair, necessitating a second open thoracic surgery. Whole-exome sequencing confirmed a novel, de novo heterozygous missense variant in the TGFBR1 gene: c.1051G>T (p.Asp351Tyr), located within the highly conserved kinase domain and classified as likely pathogenic. Structural modeling suggested that this variant enhances binding affinity to SMAD2, and immunohistochemistry of the patient's aortic tissue confirmed hyperactivation of the TGF-β pathway via increased SMAD2/SMAD3 phosphorylation. This case expands the pathogenic variant spectrum of TGFBR1-related LDS. Furthermore, it provides valuable clinical insights into the management of abdominal aortic aneurysms in LDS, suggesting that symptoms and rapid growth may warrant surgical intervention before conventional diameter thresholds are met. It also serves as a stark reminder of the residual vascular fragility, reinforcing the need for lifelong, whole-body vascular surveillance.