title: Alagille syndrome: pathogenesis, diagnosis and management.
abstract: Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is a multisystem disorder due to defects in components of the Notch signalling pathway, most commonly due to mutation in JAG1 (ALGS type 1), but in a small proportion of cases mutation in NOTCH2 (ALGS type 2). The main clinical and pathological features are chronic cholestasis due to paucity of intrahepatic bile ducts, peripheral pulmonary artery stenosis, minor vertebral segmentation anomalies, characteristic facies, posterior embryotoxon/anterior segment abnormalities, pigmentary retinopathy, and dysplastic kidneys. It follows autosomal dominant inheritance, but reduced penetrance and variable expression are common in this disorder, and somatic/germline mosaicism may also be relatively frequent. This review discusses the clinical features of ALGS, including long-term complications, the clinical and molecular diagnosis, and management.
authors.affiliation: Department of Clinical Genetics, Royal Devon and Exeter Hospital, Exeter, UK. peter.turnpenny@rdeft.nhs.uk
authors.forename: Peter D
authors.initials: PD
authors.lastname: Turnpenny
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D016738:Alagille Syndrome / Q000175:diagnosis* / Q000209:etiology*; D002135:Calcium-Binding Proteins / Q000235:genetics; D019066:Facies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D051883:Receptor, Notch2 / Q000235:genetics; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins