Presentation description

Introduction: von Hippel-Lindau (VHL) is an autosomal dominant genetic disease with an estimated incidence of less than 1:50,000. The type of germline VHL alteration has been shown to impact downstream VHL expression and clinical phenotype. However, current screening practices do not differ based on the VHL subtype. We aim to assess the genotype-phenotype association among an institutional cohort of VHL patients and evaluate the clinical manifestation differences between type 1 and type 2 patients with VHL.
Methods: This is a retrospective cohort study of 69 patients (27 families) at the University of Utah and Huntsman Cancer Institute from 1998-2023. 59% (41/69) of patients have documented germline testing results documenting VHL variant type, making this our final cohort. The association of VHL type with Hemangioblastoma (Hb), Pheochromocytoma-paraganglioma (Pheo-Para), and Renal cancer (RCC) are then summarized. VHL Type 1 can be defined as patients with VHL nonsense mutations, deletions, and frameshift mutations, and VHL Type 2 can be defined as those with missense mutations, as previously described. Using R programming, we could characterize the patients in the cohort and analyze the differences between the two VHL types.
Results: VHL type 2 comprised most of the VHL diagnoses in our cohort. Individuals diagnosed with VHL type 2 have the highest penetrance for hemangioblastoma (Hb), Pheo-Para, and renal cell carcinoma (RCC). In our study, 34% of VHL type 2 participants did not demonstrate a VHL manifestation. However, most of these patients were below the age of 20 (70%) and thus likely did not develop a manifestation yet.
Conclusions: VHL type 1 had a high prevalence for RCC and hemangioblastoma, with a notably low presence of pheo-para manifestation.