Alagille-syndroom: klinische en genetische aspecten

Alagille syndrome (ags, omim *118450) is an autosomal dominant disease that involves liver, heart, eyes, skeleton and other organs. The main characteristics are a typical facial appearance, paucity of interlobular bile ducts (pilbd) leading to chronic cholestasis, and congenital heart defects, usually involving the pulmonary arteries. In 1997 the jagged 1 gene (jag1) on chromosome 20p12 was identified as responsible for ags. Jag1 encodes a ligand in the notch signaling pathway. Ags shows large phenotypic variability. Molecular studies have shown that the complete clinical spectrum of ags can be caused by jag1 mutations.we present three families with ags. In family a, an almost 2 year old girl and her mother show the classical clinical picture with a typical facial appearance, chronic cholestasis and a congenital heart defect. Dna studies showed a splice-site mutation in the jag1 gene. In family b, the 38 year old father has typical ags features of the heart, eyes, spine and face, but lacks clinical signs of liver involvement. Two daughters died from complex pulmonary atresia. They did not have cholestasis either. This family has a cytogenetic microduplication of 20p. Dna studies did not show any abnormalities this far. The patient from family c presented with typical facial features, pilbd, peripheral pulmonary stenosis and an intracranial hemorrhage. Molecular studies showed a deletion of the jag1 gene.together with a literature review on the genotype-phenotype correlation in ags this paper underlines the clinical variability of alagille syndrome.