Work

A large French family with TGFBR2 pathogenic variant: illustration of variability

Year: 2025

Type: article

Abstract: AIMS: To report aortic events in a large family carrying a variant in the TGFBR2 gene. METHODS: Since 1990 up to 2024, we have conducted a longitudinal clinical study of a large single family comprising 63 members across four generations who carry the same TGFBR2 pathogenic variant. We assessed the incidence of aortic events and prophylactic surgery, as well as life expectancy. RESULTS: Over a follow-up, 21 patients died (33% of the population), of whom ten were related to a dissection (48%). Eight patients underwent prophylactic aortic root surgery (13%). Over the generations, there is an increase in life expectancy and a decrease in the likelihood of aortic dissection (p < 0.001), but no significant change in the combined endpoint of surgery, aortic dissection or death (p = 0.168). The type of prophylactic surgery has also evolved over the years from mechanical Bentall surgery to valve-sparing surgery. The variability in the age at onset of aortic events reflects the broad phenotypic spectrum of aortic disease associated with this variant. CONCLUSION: Across four generations, improved diagnosis, prophylactic surgery, and surgical techniques were associated with reduced dissection rates and increased survival, despite marked intra-familial variability in aortic disease severity among carriers of the same TGFBR2 pathogenic variant."

Source: Orphanet Journal of Rare Diseases

DOI: 10.1186/s13023-025-04124-1