Genetic testing for Gilbert's syndrome: how useful is it in determining the cause of jaundice?

Gilbert's syndrome is a benign condition causing hyperbilirubinemia, which is also a symptom of liver or hemolytic disease. A genetic test may be possible for Gilbert's syndrome because an associated gene defect has been isolated. Here we present a mathematical analysis of the use of this test in excluding harmful causes of hyperbilirubinemia. The effectiveness of the test depends on a low prevalence and high penetrance of the gene defect and a low prevalence of harmful hyperbilirubinemia. If the gene defect has a 12% prevalence and 10% penetrance, then the prevalence of harmful hyperbilirubinemia needs to be <1.5% for a positive test to reduce this risk fivefold. Estimates of the prevalence of harmful hyperbilirubinemia and of the prevalence and penetrance of the Gilbert genotype are required to assess the value of the genetic test in determining a cause of hyperbilirubinemia. Until these values for prevalence and penetrance are known, genetic testing for Gilbert's syndrome cannot be recommended on a routine basis.