The paucity of intrahepatic bile ducts on liver biopsy reported for the infant in the vignette suggests the diagnosis of Alagille syndrome, which is associated with systolic heart murmurs. Alagille is a familial form of chronic intrahepatic cholestatis typically presenting with neonatal cholestasis (direct hyperbilirubinemia) in the first 3 months after birth. Physical examination demonstrates a thin, jaundiced infant.
An autosomal dominant (variable penetrance and expressivity) genetic condition characterized by five principal features:
Infants usually are both short and underweight. Affected children are either cognitively normal or have mild developmental delay. Patients may experience more severe involvement of the same organ systems (eg, pulmonary arterial hypoplasia, tetralogy of Fallot, glaucoma).
Other conditions reported in Alagille syndrome include
Most cases of Alagille syndrome result from mutations in the JAGGED1 gene on chromosome 20. JAGGED1 is a ligand for NOTCH receptor, a gene important in cell differentiation, and mice that have the JAGGED1 mutation experience defects in embryogenesis.
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