Familial Von Hippel–Lindau Disease: A Case Series of Cerebral Hemangioblastomas with MRI, Histopathological, and Genetic Correlations

Von Hippel-Lindau (VHL) is a rare genetic disorder caused by mutations in the VHL gene on chromosome 3. The disease is associated with increased incidence of neoplasia. The most common manifestations of the disease are hemangioblastomas of the CNS and spinal cord, followed by renal cell carcinomas (RCC), pancreatic tumors, pheocromocytomas, endolymphatic sac tumors, and broad ligament or epididymal cystadenomas. Due to low incidence of the disease, information about its manifestation and genetic makeup has been slow to be gathered. Herein, we present three patients suffering from VHL, all part of the same family: patient one is the father; patient two is the daughter; and patient three is the nephew of the father, cousin to the daughter. Patients and their samples were investigated by magnetic resonance imaging, immunohistochemistry and genetic testing. Results show a tumor process in the left cerebellar hemisphere of the first patient which was successfully removed. The second patient presents with cervical medullary hemangioblastoma which was also successfully removed. The third patient had a tumor formation located at the craniospinal junction, at the level of the posterior bulb which was also treated. Genetic analysis showed patients one and two presented mutations in the VHL gene, confirming the VHL diagnosis. While the cases presented here follow the general lines for VHL disease, patients are related to each other, present tumors of the nervous system and mutations in the VHL gene, their particularities of presentation and manifestation bring new insights into this rare genetic disease.