Important New Information for Physicians

In the June issue of Lancet, a team of physicians from the U.S. National Institutes of Health has published an overview of von Hippel-Lindau — the clinical aspects, management, and treatment options for successful management of VHL.

The article summarizes the current state of learning on VHL, including a survey of the literature published over the past ten years. It updates many of the statistics and recommendations that have been seen in earlier papers.

"Before comprehensive screening surveys became routine, median survival of patients with the disease was less than 50 years of age [due especially to] complications linked to renal cell carcinomas and CNS hemangioblastomas. Improved surveillance, earlier diagnosis of lesions by modern imaging and laboratory studies, improvements in treatment, and increased knowledge of this disease have improved prognosis and reduced the complications related to these tumors." (p. 2059)

They include the following recommended intervals for screening in at-risk individuals, which begin at much younger ages than previous recommendations:

- Ophthalmoscopy: start in infancy, repeat yearly

- Plasma or 24 hour urinary catecholamines and metanephrines: start at 2 years of age, repeat yearly and when blood pressure is raised.

- MRI of craniospinal axis: begin at 11 years of age and repeat yearly

- CT and MRI of internal auditory canals: begin at onset of symptoms (hearing loss, tinnitus, vertigo, or unexplained difficulties of balance)

- Ultrasound of abdomen: begin at 8 years of age, and repeat yearly or substitute MRI as clinically indicated.

- Audiological function tests: begin when clinically indicated

While VHL is usually found to have been inherited in the family, it occurs for the first time in as many as 20% of families studied. Sometimes the first mutation arises as a VHL mosaicism, with the VHL gene mutation occurring in only some of the cells of the body. In such cases, "patients might have clinical signs of the disease, but test negative genetically" because the VHL mutation is not in all cells. If the mutation involves the sperm or egg cells, however, the condition can be passed to offspring, so children should be considered to be potentially at risk for VHL.

While the average age for first occurrence of retinal tumors is 25 years, "5% of retinal angiomas present in patients younger than 10 years of age." For this reason they now recommend beginning screening the retinas in infancy. "Early diagnosis and treatment can prevent visual loss or blindness."

Endolymphatic sac tumors (ELST) are rare in the general population, but are frequently associated with VHL. MRI studies found evidence of ELST in 11% of patients. "VHL is the only condition associated with bilateral ELST." Additional patients may have microscopic tumors smaller than can currently be seen on imaging, because "patients often have vestibulocochlear [inner ear] symptoms with no CT or MRI evidence of such a tumor." (p. 2062).

"The new insights into the underlying mechanisms of tumor formation, greater knowledge of the natural history of the various lesions associated with von Hippel-Lindau disease, and more precise diagnostic studies (laboratory and imaging) should lead to an improved quality of life and extend the life expectancy of affected individuals. The diverse multisystem effects of this disease need careful, selective, and coordinated planning to determine the treatment of individual lesions that will provide the best long-term management of these patients." (p. 2066)

This is an excellent overview for physicians of this complex multi-system disorder. We recommend that all specialists, general practitioners and other health professionals working with any person with VHL obtain and read this important article. The Lancet is one of the most prestigious medical journals in the world, and should be readily available through any hospital library. Patients are encouraged to share this information with their health care teams.

Reference: "Von Hippel-Lindau disease," by Lonser, Glenn, Walther, Chew, Libutti, Linehan, and Oldfield of the U.S. National Institutes of Health, Bethesda, Maryland. Lancet 361 (2003): 2059-67.