An autosomal recessive form of Alagille-like syndrome that is not linked to JAG1.

PURPOSE: Alagille syndrome is an autosomal dominant condition characterized by a paucity of interlobular bile ducts and chronic cholestasis, cardiac disease, skeletal abnormalities, ocular abnormalities, and characteristic facies. Most cases harbor a mutation in JAG1. We describe a large consanguineous family with five individuals affected with an Alagille-like syndrome that appears to be autosomal recessive. Our objective was to characterize the disorder clinically and determine whether affected individuals had inherited a mutation in JAG1.

METHODS: Clinical data were obtained through questioning and patient chart review. Linkage analysis using microsatellite markers was used to assess the possibility of a JAG1 mutation.

RESULTS: The clinical phenotype of patients was not entirely consistent with classic Alagille syndrome. All affected individuals had neonatal cholestasis with intrahepatic bile duct paucity, with three having pulmonary stenosis, but the presentation was unusually uniform and severe in childhood. There was no evidence of posterior embryotoxon or vertebral anomalies. Cardiac abnormalities were inconsistent between patients. Most significantly, the pedigree suggested an autosomal recessive form of inheritance. Linkage analysis excluded a mutation in JAG1.

CONCLUSIONS: We have identified a kindred with an Alagille-like syndrome with an autosomal recessive form of inheritance not caused by a mutation in JAG1.