Two patients with Loeys-Dietz syndrome and loss-of-function TGFBR1 variants exhibited severe but transient left ventricular systolic dysfunction that improved with medical therapy.
Case Report (n=2)
Recognition of transient cardiac dysfunction is important for tailored heart failure management in Loeys-Dietz syndrome patients with TGFBR1 variants.
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.
Hirota et al. (Mon,) conducted a case report in Loeys-Dietz syndrome (n=2). TGFBR1 variants (p.Asp400Gly and p.Leu196Pro) was evaluated on Left ventricular systolic function. Two patients with Loeys-Dietz syndrome and loss-of-function TGFBR1 variants exhibited severe but transient left ventricular systolic dysfunction that improved with medical therapy.