A rare inherited disease causes tumors in multiple organs simultaneously

Von Hippel-Lindau syndrome is a rare inherited disorder caused by a mutation in the VHL gene, a tumor suppressor gene. This mutation results in multiple simultaneous malignant and benign tumors in multiple organs of the body, including the brain, kidneys, pancreas, adrenal glands, epididymis, liver, spleen, lungs, and retina.

It occurs in one out of every 30,000 to 100,000 people, and because it is dominantly inherited, there is a 50 percent chance that it will be passed on to the patient's children.

“The VHL gene is a cancer suppressor gene. This gene prevents cancer from developing in the body,” said Professor Park Jae-young of the Department of Urology at Korea University Ansan Hospital on the Korean Organization for Rare Disease Association's YouTube channel, Angels Spoon TV.

A mutation in the VHL gene means that the cancer suppressor gene is not able to suppress cancer, Professor Park said, explaining why the disease produces multiple malignant and benign tumors.

Von Hippel-Lindau syndrome is diagnosed when multiple specific tumors are present, such as hemangioblastoma in the brain, hemangiomatosis in the retina, cysts or neuroendocrine tumors in the kidneys and pancreas, chromophilic cell carcinoma in the adrenal glands, papillary cystadenoma in the epididymis, and cysts in the liver, spleen, and lungs.

The symptoms of this disease vary. This is because the symptoms of von Hippel-Lindau syndrome vary depending on which organ is affected. “If the tumor is in the brain, it can cause headaches, for example, or if it's in the retina, it can cause vision problems,” Park said.

The average life expectancy of a patient with von Hippel-Lindau syndrome is 54 years old, and the cause of death is malignancy. The most common cause of death is central nervous hemangioblastoma, which develops in the brain and spinal cord. That’s because the central nervous system and the retina, which is adjacent to the central nervous system, are the organs with the highest incidence of malignancy.

The incidence of major malignancies in patients with von Hippel-Lindau syndrome is 61-66 percent for central nervous system hemangioblastoma, 58- 60 percent for retinal hemangioma, 28-45 percent for kidney cancer, and 18 percent for pheochromocytoma.

“If a patient with von Hippel-Lindau syndrome develops a malignant tumor, it can cause the lump to grow larger and larger or metastasize elsewhere, which can lead to death,” Park said, explaining the cause of death in patients with this syndrome.

Malignant tumors caused by the disease develop at an earlier age than most cancers.

“These cancers can occur in older adults, but on average, they occur around the age of 25,” Park said. “Central nervous hemangioblastoma is known to occur after 10.”

Kidney cancer caused by von Hippel-Lindau syndrome also has a younger age range than other kidney cancers. “While the average age of onset of kidney cancer in general is in the 50s and 60s, kidney cancer in patients with von Hippel-Lindau syndrome is known to develop after 20, with an average age of 39,” Park said.

Because the disease can cause multiple tumors in multiple organs, many tests should be done if you suspect you have the disease. A brain MRI or spinal cord MRI is needed to determine if there is central nervous system involvement, and an ophthalmoscopy to check for retinal disease. An abdominal ultrasound or CT scan is also necessary to check for cancer in the adrenal glands, kidneys, pancreas, and others.

A diagnosis of von Hippel-Lindau syndrome requires family testing.

“If the parents have it, the children should have it,” Professor Park said. “It's also possible for siblings to have the disease, so it's important for all family members to be tested to ensure early diagnosis.”

What if a family test ultimately diagnoses a patient with von Hippel-Lindau syndrome who does not yet have a tumor?

“There are no guidelines on when to start regular screening because it is an uncommon disease,” Park said while stressing that screening is essential.

“It is recommended to have a checkup once a year because there is a possibility of developing a tumor at any time, and if you have a lump or a suspicious lesion, it would be better to see it once every three to six months,” Park said. “Early diagnosis of any cancer can improve treatment and reduce the chance of dying from it. It's important to communicate frequently with your doctor to ensure you're aware of any abnormalities in your body.”