Abstract
Alagille syndrome - AGS (OMIM 118450) is a highly variable multisystem autosomal dominant disorder with incomplete penetrance. The disease is caused by mutations in JAG1 or rarely in NOTCH2.
Both genes encode extracellular signaling proteins involved in embryogenesis. Presence of pathogenic mutations leads to multiple malformations.
AGS has extremely pleitropic clinical manifestations, even within the same family members carrying the same mutations. Consequentely, there is no correlation between genotype and phenotype.
Cholestatic liver disease due to bile duct paucity with high levels of cholesterol, formation of xanthomas and a rigorous pruritus, cardiovascular anomalies (most commonly peripheral pulmonary artery stenosis), "butterfly-like" vertebrae, ophtalmologic anomalies (posterior embrytoxon) and a typical craniofacial dysmorphia including triangular face, prominent forehead, saddle nose and narrow chin represent the key clinical features of AGS. Renal, vascular and other malformations are also frequent.
Liver transplantation in childhood is necessary in cases with severe liver disease.