Korean J Pediatr.  2015 Oct;58(10):392-397. 10.3345/kjp.2015.58.10.392.

Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center

• Ahn KJ
• Yoon JK
• Kim GB
• Kwon BS
• Go JM
• Moon JS
• Bae EJ
• Noh CI

• KMID: 2085448
• DOI: http://doi.org/10.3345/kjp.2015.58.10.392

Abstract

PURPOSE
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).
CONCLUSION
The group with combined severe liver and heart disease had the poorest survival, and a multidisciplinary approach is necessary to improve the outcome.

Keyword

Alagille syndrome; Cardiovascular diseases; Pulmonary valve stenosis; Cholestasis

MeSH Terms

Alagille Syndrome*
Bilirubin
Cardiovascular Diseases
Cholestasis
Cyanosis
Embryonic Development
Female
Heart Diseases
Hemodynamics
Humans
Jaundice
Labor Presentation
Liver
Liver Transplantation
Mortality
Pregnancy
Prognosis
Pulmonary Valve Stenosis
Retrospective Studies
Bilirubin