Liver & intrahepatic bile ducts
Developmental anomalies / cysts
Alagille syndrome
Author: Kalyani R. Patel, M.D.
Topic Completed: 1 November 2016
Minor changes: 11 March 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Alagille syndrome[TI] liver[TI]
Table of Contents
Definition / general | Essential features | Pathophysiology | Clinical features | Microscopic (histologic) description | Microscopic (histologic) imagesCite this page: Patel K. Alagille syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liveralagillessyndrome.html. Accessed January 22nd, 2021.
Definition / general
- Also called arteriohepatic dysplasia
- Represents the etiology behind syndromic paucity of bile ducts
Essential features
- Genetic disorder with vascular, biliary and other anomalies
- Absence of intrahepatic bile ducts with clinical severity ranging from severe neonatal cholestasis mimicking biliary atresia to childhood intermittent jaundice
- Progression to cirrhosis is rare
Pathophysiology
- Two distinct genetic mechanisms:
- Vast majority (ALGS1) are autosomal dominant, due to mutations in Jagged1 gene on chromosome 20p12, which encodes a ligand for NOTCH1 and plays a role in epithelial mesenchymal interactions (Nat Genet 1997;16:235)
- Gene penetrance is high but expression is variable; 50 - 70% patients have new mutations
- Second genetic abnormality (ALGS2) accounting for small proportion of cases, is related to the mutations in the gene encoding NOTCH2 on chromosome 1p13 and has more severe renal disease (Am J Hum Genet 2006;79:169)
- Vast majority (ALGS1) are autosomal dominant, due to mutations in Jagged1 gene on chromosome 20p12, which encodes a ligand for NOTCH1 and plays a role in epithelial mesenchymal interactions (Nat Genet 1997;16:235)
Clinical features
- Reported incidence is 1:30,000 of live births
- Common clinical features: abnormal inverted triangular facies, posterior embryotoxon in the eye (Digital Reference of Ophthalmology: Cornea & External Diseases [Accessed 25 October 2017]), pulmonary stenosis or more severe congenital heart disease, butterfly vertebrae or other vertebral arch anomalies, other skeletal anomalies such as short distal phalanges or clinodactyly
- Several renal abnormalities such as tubulointerstitial nephropathy, membranous nephropathy, mesangiolipidosis, renovascular hypertension, etc. have been reported
- Liver findings are characterized by progressive loss of bile ducts with or without hypoplasia of extrahepatic bile ducts (Nat Genet 1997;16:235), hypoplasia of gallbladder and cholelithiasis (Nat Genet 1997;16:235) leading to jaundice and pruritus
- It can mimic other causes of high GGT cholestasis, particularly biliary atresia
Microscopic (histologic) description
- Portal tracts are devoid of bile ducts; the ratio of bile ducts to portal tracts is 0 to 0.4 (normal 0.9 to 1.8) (Pediatr Pathol 1988;8:1)
- Ductular reaction is typically absent but rare examples present with ductular reaction in early infancy (Nat Genet 1997;16:235)
- Giant cell transformation and periportal copper deposits can be seen
- Progression to cirrhosis is rare
Microscopic (histologic) images
Contributed by Dr. Kalyani R. Patel
Various images
