Alagille syndrome is a multisystem disorder with significant ocular, skeletal, vascular, hepatic, and renal manifestations. Ductular hypoplasia with cholestasis is the hallmark of the hepatic disease. The kidneys are often cystic (more severe in the type II variant of Alagille syndrome). The skeletal findings include "butterfly" vertebrae, short stature, brachydactyly, broad forehead, and a pointed chin. The tip of the nose often appears bulbous. Vascular abnormalities include major vessel aneurysms, valvular insufficiency, coarctations of the aorta, and stenosis of the pulmonary artery. 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.
ICD10CM: Q44.7 – Other congenital malformations of liver
SNOMEDCT: 31742004 – Arteriohepatic dysplasia
Differential Diagnosis & Pitfalls
The presence of cholestatic liver disease alone is insufficient to make the diagnosis since many other causes exist. Dysplasia of the biliary tree is the cardinal hepatic feature. It is also a feature of another rare heritable disorder known as autosomal recessive progressive familial intrahepatic cholestasis (Byler disease). However, no ocular abnormalities or characteristic facial morphology is present in this condition. Meckel syndrome may be associated with biliary malformations, but the ocular features primarily consist of major globe deformities. Deformities of the anterior chamber of the eye in Alagille syndrome are not diagnostic, since they can occur in isolation or as part of numerous syndromes. Their presence always requires a full systemic evaluation.