Inheritance: a third to half of patients show autosomal dominant inheritance and the remainder show de novo mutations.
Parameters:
(1) affected first degree relative
(2) histologic evidence of bile duct paucity in a liver biopsy (this finding may be present during infancy or become evident later)
(3) number of major clinical findings
Major clinical findings:
(1) cholestasis
(2) stenosis of peripheral pulmonary artery or other cardiac defect
(3) butterfly vertebrae or other skeletal defect
(4) posterior embryotoxon or other ophthalmologic abnormality
(5) characteristic facial features
Clinical diagnosis can be made by:
(1) (affected first degree relative) AND (1 or more clinical findings)
(2) (paucity of bile ducts) AND (3 or more major clinical findings)
Ultimately diagnosis depends on demonstration of a mutation in JAG1 or NOTCH2.
