In the absence of a family history of VHL the presence of two or more retinal or cerebellar hemangioblastomas, or one hemangioblastoma with one visceral tumor, is required for diagnosis. Studies of the natural history of VHL showed a life expectancy less than 50 years before surveillance protocols were developed. Imaging of abdominal organs and the brain and spine should be added in teenagers and adults. Renal cysts and tumors should be monitored by computed tomography every 6 months. The VHL gene coding sequence contains three exons, and two isoforms of mRNA exist, reflecting the presence or absence of exon 2.
Tumors arise after the loss or inactivation of the wild type allele in a cell.
Most type 2 families have missense mutations, whereas most type 1 families are affected by deletions or premature termination mutations. AD - Department of Pediatrics, University of Padua, Italy. In the course of a molecular analysis conducted to detect germline mutations of this gene in von Hippel-Lindau patients and individuals affected by sporadic tumors, we have identified a case of somatic mosaicism in the asymptomatic mother of a VHL patient who was subsequently diagnosed with pheochromocytoma. This is the first report providing molecular evidence of somatic mosaicism in von Hippel-Lindau disease. Mosaicism could provide some genetic explanation for the clinical heterogeneity and variable severity of the VHL phenotype, and should be considered, as a possible event when evaluating sporadic cases of VHL or patients with isolated VHL-related tumors.