What Is Von Hippel-Lindau Disease? Where Does Its Name Come From?

Von Hippel-Lindau (VHL) disease is a cancer syndrome associated with germline (hereditary) mutations in the VHL gene. Although most VHL disease cases are familial, 20% result from nonhereditary mutations.

Patients with VHL disease develop multiple tumors in different organs, such as the brain, kidneys, adrenal glands, pancreas and reproductive organs. These tumors may be either cancerous or benign.

Deaths related to VHL usually result from complications associated with renal cell carcinoma (kidney cancer) and brain tumors. Early intervention in patients with VHL disease may prevent or delay additional health problems and death, so for this group we recommend age-specific cancer screening as an approach.

The History of Its Name

Dr. Eugen von Hippel, a German ophthalmologist (eye disease specialist), and Dr. Arvid Lindau, a Swedish pathologist, gave VHL disease its name.

Dr. von Hippel was born in Königsberg, Germany, in 1867 and died in 1939. Working in internal medicine, pathology and ophthalmology, he was a professor at Heidelberg University from 1892 to 1909, Halle University from 1909 to 1914, and Göttingen University from 1914 until his retirement in 1934.

Dr. von Hippel described the clinical and histological features of retinal hemangioblastomas. However, he never established a connection between retinal hemangioblastoma and VHL disease.

Dr. Lindau was the first to connect the systemic features of VHL disease with retinal and craniospinal hemangioblastoma.

Dr. Lindau was born in Malmo, Sweden, in 1892 and died in 1958. After completing his master's and doctoral studies at Lund University, he became a professor there in 1933 and also served as a military physician from 1924 to 1934.

While studying cadavers with cerebellar hemangioblastomas, Dr. Lindau found cysts in the pancreas, liver and kidneys, as well as pheochromocytomas and hemangioblastomas of the liver, spinal cord and retina.

Based on these and subsequent findings, Dr. Lindau proposed that visceral and nervous system lesions occurring alongside retinal vascular changes represented a single disease process.

Because of this work, the condition was initially proposed to be called “Lindau Disease”. However, due to Dr. von Hippel's original description of retinal hemangioblastomas, “von Hippel” was added in the 1930s, and the condition was named “Von Hippel-Lindau Disease”.

Discovery of the VHL Gene

Although VHL disease is now known as a hereditary genetic cancer syndrome, discovery of the VHL gene had to wait until 1993. In 1993, F. Latif and colleagues published in Science a groundbreaking paper entitled "Identification of the von Hippel-Lindau disease tumor suppressor gene". After noting that the VHL gene itself was small, comprising 854 nucleotides in 3 exons encoding 284 amino acids, the paper described it as an important tumor suppressor gene. Changes in a tumor suppressor gene predisposed the person to multiple tumors. Most kidney cancers were found to harbor VHL gene abnormalities, strongly suggesting that the same gene was responsible for both hereditary and nonhereditary forms of the disease.

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Related topic: Belzutifan Receives FDA Approval to Treat Cancers Associated with Von Hippel-Lindau Disease