Alagille syndrome is an autosomal dominant multisystem disorder with significant ocular, skeletal, cardiovascular, hepatic, and renal manifestations. Defects in the Notch signaling pathway such as Jagged1 (JAG1) mutations and less commonly NOTCH2 mutations are causative.

Ductular hypoplasia with cholestasis is the hallmark of the hepatic disease. Severe, early-onset pruritus from cholestasis is a common disease manifestation. Chronic cholestasis can lead to hypercholesterolemia, cirrhosis, and hepatic failure, and cases of hepatocellular carcinoma have also been described. Some individuals have such mild disease that the diagnosis may not be made until adulthood. However, the majority of patients have evidence of liver disease in the first 3 months of life. It is not possible to predict which infants will develop progressive disease, but among children under the age of 5 years, a total bilirubin greater than 6.5 mg/dL and cholesterol greater than 520 mg/dL are associated with more severe liver disease as adults.

The kidneys are often cystic (more severe in the type II variant of Alagille syndrome). Vascular abnormalities include major vessel aneurysms, valvular insufficiency, coarctations of the aorta, and peripheral pulmonary stenosis. Septal defects are also common (eg, ventricular septal defect as well as tetralogy of Fallot). Focal or diffuse hyperintensity of white matter may be seen on the MRI of the brain. All features are highly variable among patients. The anterior chamber ocular findings are considered by some to be characteristic of Axenfeld anomaly (otherwise known as posterior embryotoxon or anterior displacement of Schwalbe's line), but they are often accompanied by abnormal fundus pigmentation such as hypopigmentation, pigment clumping, and sometimes diffuse pigment speckling. In addition, optic disc anomalies (hypoplasia, atrophy, tilting, peripapillary depigmentation, drusen) have been reported in upward of 76% of individuals. The corneas in patients with this syndrome are usually smaller than normal, but no unusual refractive errors are present.

The skeletal findings include "butterfly" vertebrae, short stature, brachydactyly, broad forehead, and a pointed chin. The tip of the nose often appears bulbous.