Presentation Authors: Jiangyi Wang*, Shanghai, China, People's Republic of, Kan Gong, beijing, China, People's Republic of
Introduction: Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, which neglected the obvious inter and intra familial phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying mechanism.
Methods: A total of 151 parent-child pairs were enrolled for genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical methods were used to compare the onset age of patients among different generations and different birth orders.
Results: The average onset age was 18.9 years earlier in children than that in their parents, which was statistically significant in paired t test (p < 0.001), RY1 (p < 0.05), RY2 (p < 0.01) and CPH model (p < 0.001). Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in VHL families, while it failed to explain the birth order effect. Moreover, no significant difference was observed for overall survival between parents and children (p=0.834) and between the first-born patients and the other siblings (p=0.390).
Conclusions: This study provides definite evidence and possible mechanisms of intra-familiar phenotypic heterogeneity in VHL families, which is helpful to the update of surveillance guidelines.