Predictive diagnosis in familial adenomatous polyposis: evaluation of molecular genetic and ophthalmologic methods

Familial adenomatous polyposis (FAP) is an autosomal-dominant precancerous condition characterized by the appearance of hundreds to thousands of colorectal polyps. The responsible gene (APC) has been mapped and identified. The cancer prevention policy for persons at risk (children and sibs of FAP patients) implies an early diagnosis of the disease. A presymptomatic diagnosis allows to limit the regular rectosigmoidoscopic examination to those persons having inherited the disease gene. Presymptomatic diagnosis can be achieved by molecular genetic methods (direct and indirect genotype analysis) and by funduscopic examination of retinal pigment anomalies that are characteristic for FAP. The aim of this study was to examine the power of the molecular genetic and ophthalmologic methods for presymptomatic diagnosis in FAP. For this purpose 60 FAP families with 171 persons at risk were examined. By direct mutation analysis a presymptomatic diagnosis was achieved in 32% of the persons at risk; indirect genotype analysis was possible in 88% of the families in which more than one FAP patient was available. The ophthalmologic examination allowed a presymptomatic conclusion in 79% of the persons at risk. In no case there was a discrepancy in the results between the methods applied. The ophthalmologic presymptomatic test is useful especially in families where the index patients has a new mutation in the APC gene that has not been identified.