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The Fourth International Symposium on von Hippel-Lindau, July 20-23, 2000, in Rochester, Minnesota, consisting of 180 assembled researchers, physicians, and members of affected families from 17 countries agreed on the following conclusions from the meeting:
DNA testing in childhood
- Genetic testing for VHL in early childhood is justified
- because of early age at onset
- because of availability of treatment
- It is still the choice of the individual family whether to perform DNA testing in childhood. However, all untested children must be considered to be at risk for VHL, and preventive screening is essential.
- A genetics professional should be involved prior to any DNA testing (children or adults).
- This symposium strongly disagrees with the misuse of DNA status information by insurance companies, employers, or others. DNA status information should be used only for the medical benefit of the patient and in any research to which the patient has agreed.
Prevention
- Based on data from NIH, people with VHL are advised not to smoke, and to reduce their exposure to second-hand smoke.
- People with VHL should be alerted that there is evidence (Brauch et al) to suggest that exposure to Trichlorethylene and associated substances may accelerate VHL. Confirming evidence is needed before recommendations can be made.
- Families in Japan have a significantly lower rate of eye tumors than people with similar genotypes in other parts of the world. This may prove important for prevention.
Adrenal
- Dr. Green recommends screening from age 3-4
- There is compelling evidence (Lenders et al) that Plasma free metanephrines (PFM) is the most sensitive and specific test for pheochromocytoma. We are encouraged by these results, and believe that PFM can be a useful adjunct to existing testing methods. Standards for children still need to be established.
- Guidelines for drawing blood and submitting samples for analysis to NIH or Mayo Clinic can be found through http://www.vhl.org/pheo
- Clinical neurochemistry laboratory procedures for laboratories interested performing this test are available at http://www.catecholamine.org
- Because very small tumors can be identified in this manner, it is important to have a threshhold for watching/operating on tumors.
- Adrenal-sparing surgery should be the standard of care for people with VHL.
- Organ-sparing adrenal surgery should be performed laparoscopically whenever possible.
Kidney: When to Operate
- The "3-cm. Rule" is still the guideline for watching kidney tumors. This is based on data from centers worldwide, which does show considerable variation. There is still some small risk of metastasis (less than 1%) which should be disclosed to the patient. Any relevant familial variations should be taken into account.
Pancreas
- Screening of the pancreas is important.
- Tumors may be observed up to 2-3 cm.
- Surgery to drain cysts should only be undertaken when needed to manage pain.
- Organ sparing surgery is preferred when surgery is necessary.
- We are encouraged by early results, and would like to see continued evaluation of PET to assist in distinguishing neuroendocrine tumors from cysts.
CNS
- Risk of spontaneous hemorrhage of spinal lesions is very low (0% in Sarkar study)
- Need for a retrospective study of CNS lesions treated with stereotactic radiosurgery with longer follow-up, to rule out periods of quiescence and evaluate danger of longer-range complications
- Presymptomatic screening for brain and spinal cord lesions is critical to maintaining health and function, to monitor growth rates and make informed decisions about course and timing of action.
- An appropriate program of screening and counseling has been proven to dramatically reduce morbidity, fatality, and anxiety among people with VHL.
Review of Screening Guidelines
We reviewed the Screening Guidelines in the Handbook and suggested the following changes, underscored, for consideration of the Medical Advisory Board and possible inclusion in the next revision of the Handbook:
From Conception
- inform obstetrician, communication among doctors
From birth
- inform pediatrician of family history
Ages 2-10
- annual physical & neuro assessment by pediatrician informed about VHL (BP, neuro, nystagmus, pupil)
Beginning about age 3-5
- eye exam with indirect ophthalmoscope or better
- test for elevated catecholamines in 24-hour urine, or with plasma free metanephrines where available
Note: The age to begin screening was reduced from 4-6 to 3-5 based on data from several participants indicating more eye and pheo involvement in young children than had previously been thought. Earlier treatment of eye lesions can save vision; many reported data that pheos are best treated in their early stages of development, before they become sufficiently active to cause heart and vascular complications or have a pheo incident provoked by a minor accident.
Ages 11-19
- every 6 months: eye exam
- annually: physical with informed pediatrician
- include baseline scrotal examination in males*
- test for elevated catecholamines in 24-hour urine, or with plasma free metanephrines where available. This test should be performed before any surgery, or if pregnant.
- ultrasound of abdomen, including ovaries in females
- every two years: MRI with gadolinium of brain and spine. Annually at onset of puberty or before and after pregnancy, or before any surgery.
Note: There was a discussion whether to keep or omit the scrotal check since action is not taken unless there is rupture. It was decided that as good ongoing practice for all men for the early detection of testicular cancer (analogous to breast self-examination in women), and as a baseline in case of any questions, this manual check should remain. Ultrasound only if deemed necessary.
Age 20 and beyond:
- eye exam with indirect ophthalmoscope
- quality ultrasound
- at least every other year, CT of abdomen w w/o contrast, but NOT during pregnancy, including review of any possible APMO's in females
- ultrasound preferred during reproductive years
- physical exam by informed physician
- test for elevated catecholamines in 24-hour urine, or with plasma free metanephrines where available
- every two years: MRI with gadolinium of brain and spine (and before and after pregnancy)
- audiometric exam. If hearing loss, tinnitus, vertigo, then add MRI of Internal Auditory Canal.
Requests for Padua
- Please include APMO’s in the screening, to serve as a baseline in case of gynecological questions.
- Please report all genotype/phenotype information to the French VHL database (available through www.vhl.org/research). Grouping this data in a consistent format will give everyone a larger pool of data on which to base research.
- Need a study of factors contributing to earlier versus later metastasis of kidney tumors:
- Specific mutations?
- Modifier genes?
- Other characteristics?
- Seem to have familial variations in time-to-met
- Need for a retrospective study of CNS lesions treated with stereotactic radiosurgery with longer follow-up, to rule out periods of quiescence and evaluate danger of longer-range complications.
- Need a study of the effects of hormone shifts or hormone levels in women (adolescence, pregnancy, going on/off the pill, menopause). If a protocol can be written to gather data from women in a consistent way, the women of the VHLFA will gladly participate in such a study.
Teamwork for Health
Families and Health Care Professionals
working together
to improve diagnosis, treatment, and
quality of life
for individuals and families
affected with von Hippel-Lindau
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