A variety of systemic features, some of them serious malformations, occur in Alagille syndrome. Among the most common is a partial intrahepatic biliary atresia leading to cholestasis and jaundice. Skeletal malformations include 'butterfly' vertebrae, shortened digits, short stature, a broad forehead, and a pointed chin. The tip of the nose may appear bulbous. These features have suggested to some that there is a characteristic facial dysmorphology. Vascular malformations are common including aneurysms affecting major vessels, valvular insufficiency, coarctation of the aorta, and stenosis and these are often responsible for the most serious health problems. In fact, vascular events have been reported to be responsible for mortality in 34% of one cohort. Chronic renal insufficiency develops in a minority of patients. This disorder should always be considered in children with cholestasis, especially when accompanied by cystic kidney disease. Brain MRIs may show diffuse or focal hyperintensity of white matter even in the absence of hepatic encephalopathy.
