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Alagille disease

Saturday 31 May 2003

Digital cases

- Case 117 (HPC:117) : Hepatocellular carcinoma in Alagille disease

Definition: Alagille syndrome is an autosomal dominant, multisystem disorder with variable expressivity, characterized by bile duct paucity and resultant liver disease in combination with cardiac, ocular, skeletal, and facial findings.

Synopsis

- characteristic face

  • broad forehead
  • triangular face
  • prominent zygomatic arch
  • long nose with bulbous tip

- ocular anomalies

  • deep-set eyes
  • posterior embryotoxon
  • posterior chamber anomalies
  • eccentric pupils or ectopic pupils
  • chorioretinal atrophy
  • retinal pigment clumping
  • axenfeld anomaly
  • choroidal folds
  • strabismus
  • myopia
  • anomalous optic disc
  • posterior embryotoxon

- biliary lesions

  • paucity of interlobular bile ducts (hepatic ductopenia, hepatic ductular hypoplasia, intrahepatic bile duct hypoplasia)
  • intrahepatic biliary atresia
  • extrahepatic biliary atresia (#12297837#)

- cardiovascular lesions

  • peripheral pulmonary artery stenosis
  • tetralogy of Fallot
  • atrial septal defect
  • ventricular septal defect
  • coarctation of aorta

- renal Alagille disease

  • renal dysplasia
  • renal mesangiolipidosis
  • medullary cystic disease
  • chronic renal failure and hypertension

- rib anomalies
- vertebral anomalies
- butterfly vertebral arch
- hemivertebrae

- hands

  • short ulnae
  • short distal phalanges

Associations

- hepatocellular carcinoma (Case 117)
- papillary thyroid carcinoma

Etiology

- mutation of Jagged1 (JAG1 gene) of the Notch signaling pathway

  • JAG1 mutations in AGS include gene deletions and protein truncating, splicing, and missense mutations, suggesting that haploinsufficiency is the mechanism of disease causation.

The cardiac-specific phenotype associated with this mutation suggests that the developing heart is more sensitive than the developing liver to decreased dosage of JAG1. (#12649809#)

References

- Libbrecht L, Spinner NB, Moore EC, Cassiman D, Van Damme-Lombaerts R, Roskams T. Peripheral bile duct paucity and cholestasis in the liver of a patient with Alagille syndrome: further evidence supporting a lack of postnatal bile duct branching and elongation. Am J Surg Pathol. 2005 Jun;29(6):820-6. PMID: #15897750#

- Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987 Feb;110(2):195-200. PMID: #3806290#

- Berard E, Sarles J, Triolo V, Gagnadoux MF, Wernert F, Hadchouel M, Niaudet P. Renovascular hypertension and vascular anomalies in Alagille syndrome. Pediatr Nephrol. 1998 Feb;12(2):121-4. PMID: #9543369#

- Habib R, Dommergues JP, Gubler MC, Hadchouel M, Gautier M, Odievre M, Alagille D. Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia). Pediatr Nephrol. 1987 Jul;1(3):455-64. PMID: #3153318#

- Alagille D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. 1975 Jan;86(1):63-71. PMID: #803282#

Portfolio

  • Hepatocellular carcinoma and cirrhosis in Alagille
  • Hepatocellular carcinoma and cirrhosis in Alagille disease