title: Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center.
abstract: OBJECTIVE
  Alagille syndrome is a complex hereditary disorder that is associated with cardiac, hepatic, skeletal, ocular, and facial abnormalities. Mutations in the Notch signaling pathway, such as in JAG1 and NOTCH2, play a key role in embryonic development. A cardiac or hepatic presentation is a critical factor for determining the prognosis.
  
  
  METHODS
  We conducted a retrospective study of 41 patients with Alagille syndrome or a JAG1 mutation between 1983 and 2013.
  
  
  RESULTS
  The first presentations were jaundice, murmur, cyanosis, and small bowel obstruction at a median age of 1.0 months (range, 0-24 months). The JAG1 mutation was found in 27 of the 28 genetically-tested patients. Cardiovascular anomalies were identified in 36 patients, chronic cholestasis was identified in 34, and liver transplantation was performed in 9. There was no significant correlation between the severity of the liver and cardiac diseases. The most common cardiovascular anomaly was peripheral pulmonary stenosis (83.3%), with 13 patients having significant hemodynamic derangement and 12 undergoing surgical repair. A total bilirubin level of >15 mg/dL with a complex surgical procedure increased the surgical mortality (P=0.022). Eight patients died after a median period of 2.67 years (range, 0.33-15 years). The groups with fetal presentation and with combined severe liver and heart disease had the poorest survival (P<0.001).
  
  
  CONCLUSIONS
  The group with combined severe liver and heart disease had the poorest survival, and a multidisciplinary approach is necessary to improve the outcome.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Ja Kyoung
authors.initials: JK
authors.lastname: Yoon
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Gi Beom
authors.initials: GB
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Bo Sang
authors.initials: BS
authors.lastname: Kwon
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Go
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Moon
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Bae
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Chung Il
authors.initials: CI
authors.lastname: Noh
keywords: Alagille syndrome; Cardiovascular diseases; Cholestasis; Pulmonary valve stenosis