Alagille Syndrome: Phenotypes, Genotypes, and Outcomes

Alagille syndrome is an autosomal dominant multisystem disorder caused by pathogenic variants in JAG1 or NOTCH2, occurring in approximately 1 in 30,000 to 50,000 live births. Disrupted Notch signaling impairs biliary morphogenesis and affects cardiac, renal, skeletal, and ocular systems. Neonatal cholestasis is the most common presentation and clinically significant feature. Accurate diagnosis is critical, as misdiagnosis of biliary atresia increases transplantation risk. Next-generation sequencing panels enable rapid molecular confirmation. Ileal bile acid transport inhibitors have improved symptom management, and liver transplantation remains a definitive therapy for hepatic complications.