Genetic factors in neonatal hyperbilirubinemia and kernicterus.

Although the relationship between hyperbilirubinemia and genetic factors has long been questioned, the role of genetic factors in the development of severe hyperbilirubinemia and kernicterus has been investigated in detail in the last decade with the rapid progression in molecular medicine. Although the first historical data gathered about genetical tendency to neonatal hyperbilirubinemia dates back to description of the Crigler-Najjar syndrome in 1952, a substantial interest is currently focused on coding and promoter region mutations of uridine diphosphoglucuronate glucuronosyltransferase 1A1 gene. In this article, the role of uridine diphosphoglucuronate glucuronosyltransferase gene mutations in neonatal significant hyperbilirubinemia and kernicterus is reviewed together with the clinical presentations of the most common syndromes of bilirubin conjugation, such as Gilbert and Crigler-Najjar syndromes. Genetic counseling and investigation may be useful and necessary in newborns presenting with severe, unexplained familial hyperbilirubinemia. In these various syndromes where enzymatic and genetic deficiencies are present, studies about treatment with gene replacement, though currently experimental, are ongoing, especially in type 1 Crigler-Najjar.