JACC Case Rep. 2026 Jun 3:108608. doi: 10.1016/j.jaccas.2026.108608. Online ahead of print.
ABSTRACT
BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by vascular and valvular diseases. TGFBR1 is a major causative gene, mediating disease progression through dysregulated transforming growth factor-β signaling; however, its role in left ventricular systolic function remains unclear.
CASE SUMMARY: We report 2 LDS cases harboring TGFBR1 variants (p.Asp400Gly and p.Leu196Pro). Severe left ventricular systolic dysfunction was observed in these patients but improved with initiation and optimization of medical therapy. Histopathologic analysis of right ventricular biopsy specimens revealed limited interstitial and perivascular fibrosis. Functional analysis demonstrated reduced transforming growth factor-β signaling activity associated with both variants and decreased protein expression of TGFBR1-Asp400Gly.
DISCUSSION: These findings suggest a potential loss-of-function effect of TGFBR1 variants in LDS, and the clinical course including transient cardiac dysfunction provides important insights into future medical management for LDS.
TAKE-HOME MESSAGE: Recognition of transient cardiac dysfunction is important for tailored heart failure management in LDS patients with TGFBR1 variants.
PMID:42240538 | DOI:10.1016/j.jaccas.2026.108608