Impact of the molecular and clinical screening in Brazilian families with von Hippel-Lindau disease (VHL)

JCC Rocha, MD, a AA Camargo, PhD, RLA Silva, PhD, O Caballero, MD PhD b, AJG Simpson, PhD b

a Hospital do Cancer AC Camargo - Sao Paulo, bLudwig Institute for Cancer Research - Sao Paulo branch, Sao Paulo, Brazil

Aim: to evaluate the impact of the molecular and clinical screening program in Brazilian families with VHL. Methods: 20 VHL families and 3 de novo VHL patients were included. All patients received genetic counseling and DNA was extracted from peripheral lymphocytes. Mutation detection consisted of direct sequencing of the 3 exons of the VHL gene, and quantitative Southern-blot. After the identification of the deleterious mutation in the proband, the test was offered to non-symptomatic relatives to verify the carrier status. 105 individuals, including 56 VHL patients and 49 non-symptomatic relatives were studied. Periodic follow-up with clinical and radiological screening was performed in all individuals. Results: Germ line mutations in the VHL gene were detected in all probands and consisted of 17 point mutations (5 new) and 6 rearrangements. Ten carriers were identified and the disease could be excluded in 25 high risk relatives. During the follow up (6 months to 4 years) we detected a sort of non-symptomatic associated lesions, and proper intervention was performed individually. Conclusions: Molecular diagnosis of VHL permitted the screening of non-symptomatic family members with high risk, the refinement of risk analysis with an individualized genetic counseling based on the genetic risk, and an appropriated follow up of carriers. The clinical screening program had a positive impact in the course of the disease in these Brazilian families, with a reduction of the morbidity as a result of the early diagnosis and treatment of associated lesions.

KEY WORDS: von Hippel-Lindau, molecular diagnosis, counseling.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Familial and Hereditary Cancer.