The University Hospital, Utrecht, has periodically screened members of a large affected family since 1976. Three family members had already died when the disease was first named in the proband, the initial patient studied, the fifth of nine children. ( See Figure 1) His father had died of metastatic renal cell carcinoma at age 55. Hospital records of two of his sisters indicated that they had died of cerebellar hemangioblastomas at 39 and 32 years respectively. Twenty-three family members underwent screening, (the primary patient’s six other siblings and their 18 children, nieces, and nephews) of whom 9 were found to have VHL.

fig one

Four have angiomas of the eye, thirteen have renal lesions, four have pheochromocytomas, four had pancreatic lesions. Liver cysts were found in two patients. Small cystadenomas in the epididymis were found in two patients, and a cystadenoma in the broad ligament in one patient.

In the eye, "the finding of twin vessels may be an early diagnostic sign of the disease." Twin vessels are where a tiny vein and a tiny artery are paired near the optic disk. "Twin vessels can also be found in the normal population," but while they occur in 5.5% of the general population, they occur in 64% of people with VHL.

In the kidney, "CT scanning is found to be more reliable than ultrasound in distinguishing renal cysts from renal cell carcinoma." However, the Utrecht team recommends using annual ultrasound for most follow-ups, to reduce the exposure to radiation. Radiation is known to cause genetic mutation, which may be associated with the transformation of normal cells into tumor cells.

This group advocates a conservative approach to treatment of kidney tumors. "Only solid and progressively growing lesions with a diameter of more than 3-4 cm. should be surgically removed. Partial nephrectomy is an attractive alternative and has produced favorable results. . . . If bilateral nephrectomy is indicated, kidney transplantation is a reasonable option in the long run." However, the risk of developing any cancer is increased in people whose immune system is suppressed. "One may speculate whether immunosuppression enhances the development of VHL lesions." [p. 165]

Diagnosis of pheochromocytomas remains tricky.² This group recommends refraining from treating pheochromocytomas until they become chemically active, or until the tumor shows steady growth. "However the behavior of pheochromocytoma remains unpredictable; biologically inactive pheochromocytomas may suddenly become dangerous." This is especially true under markedly increased stress, such as any kind of accident or surgery. MIBG scintigraphy³ is important to find any pheos which may occur outside the adrenal glands.

"VHL is a potentially malignant disease, which requires careful family screening. CNS hemangioblastoma and renal cell carcinoma are the most treacherous." For a person who carries the VHL gene, regular lifelong screening is required to maintain health by ensuring timely and appropriate treatment. "Clear oral and written information has to be provided to the families about clinical symptoms, signs, complications, treatment, prognosis, and inheritance of the syndrome. Early recognition may prevent patients’ and doctors’ delay.

"The disease can greatly impact a family’s sense of physical and emotional well being. Recently, VHL family members have initiated the publication of the VHL Family Forum to share experiences and information. This newsletter will facilitate communication among patients, close family members, and health care workers and contribute to care for families."

1. Nicky Karsdorp, Arthur Elderson, Dienke Wittebol-Post, Ronald J. Hené, Jaap Vos, Michiel A. M. Feldberg, Adriaan P.G. van Gils, Johanna Jansen-Schillhorn van Veen, Thea M. Vroom, Jo W. M. Hoppener, Cornelis J.M. Lips, "Von Hippel-Lindau Disease: New Strategies in Early Detection and Treatment," American Journal of Medicine, 97:158-168, Aug 1994.

2. See Graham, "The Many Masks of Adrenal Involvement," VHLFF, December 1993. See also Neumann et al., N.E. J. Med., 329:1531-1538 (1993).

3. A nuclear medicine test for pheochromocytoma. See Graham or Neumann articles in footnote 2.

As published in the VHL Family Forum, 3:1, March 1995. For permission to reprint, please contact the VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.