Classic Alagille syndrome criteria Bile duct paucity plus of major criteria: • “Alagille Facies” • Cholestasis (conjugated hyperbilirubinemia) • Congenital heart disease • Vertebral anomalies • Ocular anomalies Additional clinical characteristics Hepatic: chronic cholestasis, portal hypertension, liver fibrosis, liver cirrhosis, liver failure, hepatocellular carcinoma Cardiac: tetralogy of Fallot, pulmonic valve stenosis, pulmonary atresia, truncus arteriosus, aortic stenosis, ASD and VSD Ocular: posterior embryotoxon, Axenfeld anomaly, Rieger anomaly, congenital macular dystrophy, cataracts, exotropia, strabismus, retinal fundus hypopigmentation Vertebral: butterfly vertebrae, shortened digits, spina bifida occulta, fusion of adjacent vertebrae, rickets, osteopenia/osteoporosis, pathologic fractures Facial features: prominent forehead, macrocephaly, hypertelorism, deep set eyes, upslanting palpebral fissures, depressed nasal bridge, sinus abnormalities, large ears Renal: renal tubular acidosis, renal insufficiency, small/ectopic/horseshoe/single kidneys, renal cysts Vascular: stroke, intracranial bleeding, cerebral artery anomalies, vascular malformations, moyamoya syndrome, renal artery stenosis Endocrine: pancreatic exocrine insufficiency, insulin-dependent diabetes mellitus, hypogonadism Gastrointestinal: malabsorption, failure to thrive, malrotation, microcolon, atresia Other: growth retardation, mental retardation, learning difficulties