Liver and intrahepatic bile ducts - nontumor
Developmental anomalies / cysts
Alagille syndrome

Author: Kalyani R. Patel, M.D. (see Authors page)

Revised: 15 November 2016, last major update November 2016

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Alagille syndrome liver
Cite this page: Alagille syndrome. website. Accessed September 26th, 2017.
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
  • 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)
Clinical features
  • Reported incidence is 1:30,000 of live births
  • Common clinical features: abnormal inverted triangular facies, posterior embryotoxon in the eye, 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
  • Liver transplantation is reserved for patients with progressive liver disease or intractable pruritus
  • Mortality is related to liver disease, cardiac abnormalities and intracranial bleeding
  • Patients may survive into adulthood, but with increased risk of hepatic failure and hepatocellular carcinoma
  • Microscopic (histologic) images

    Images hosted on Pathout server:
    Missing Image

    Contributed by
    Kalyani R. Patel, M.D.