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

 rib anomalies
 vertebral anomalies
 butterfly vertebral arch
 hemivertebrae

 hands

• short ulnae
• short distal phalanges

 renal anomalies

• renal dysplasia
• renal mesangiolipidosis
• medullary cystic disease

Associations

 hepatocellular carcinoma
 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

 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#