An infant with persistent conjugated hyperbilirubinemia undergoes liver biopsy showing a paucity of interlobular bile ducts. She has a systolic murmur from peripheral pulmonary stenosis, butterfly vertebrae on spine radiograph, and slit-lamp examination reveals a prominent Schwalbe line with attached iris strands. Which gene is mutated?

• A CFTR
• B ATP7B
• C ABCB4
• D JAG1 ✓

Explanation

Alagille syndrome is caused by mutations in JAG1 (or NOTCH2 in a minority) and combines cholestatic liver disease from interlobular bile duct paucity with peripheral pulmonary stenosis, butterfly vertebrae, and posterior embryotoxon on corneal examination. The embryotoxon described here is the ocular hallmark. ABCB4 causes progressive familial intrahepatic cholestasis type 3, ATP7D causes Wilson disease, and CFTR causes cystic fibrosis liver disease with normal duct numbers early.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.