Endocrine Abstracts

Background: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumour syndrome with an important phenotypic variability. Genetic testing for VHL is simple and accurate.

Objective: In this study, we investigated the relationships between genotype and phenotype in a series of patients with different VHL gene mutations.

Method: This was a retrospective analysis of the clinical and molecular characteristics of 15 VHL patients followed between 1965 and 2012 at the Cliniques Universitaires Saint-Luc. Patients were divided into two groups in order to investigate possible differences in tumour risk and age of onset. Group 1 included six patients with missense mutations, while group 2 comprised nine patients with nonsense mutations (n=7), gene deletion (n=1) or gene insertion (n=1).

Results: The mean age at onset of symptoms was 20.6±9.1 years. Retinal (27%) and CNS haemangioblastomas (27%) were the most frequent initial presentations. In three cases (20%), the initial presentation was a phaeochromocytoma. The cumulative occurrence was 93% for cerebellar haemangiomas (mean age 28.7 years), 67% for retinal haemangiomas (mean age 25.8 years), 47% for renal cancer (mean age 38.2 years), 53% for phaeomochromocytoma (mean age 27.1 years), 53% for multiple pancreatic cysts (mean age 31.8 years) and 33% for pancreatic neuroendocrine tumours (mean age 34.8 years). Eleven different VHL mutations were found: nine mutations in unrelated VHL patients and two mutations in two different kindreds. Patients from group 1 tended to have more frequently a phaeochromocytoma (4/6, 66,7%) than patients from group 2 (4/9, 44,4%), while patients from group 2 tended to have more frequently a endolymphatic sac tumour (3/9, 33,3%) than patients from group 1 (0/6). When we compared prevalence and age of onset of the other types of tumours, we did not find significant differences between the two groups.

Conclusions: In our study there was no significant difference in the phenotype of patients with missense vs nonsense gene alterations.