Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center.
10.3345/kjp.2015.58.10.392
- Author:
Kyung Jin AHN
1
;
Ja Kyoung YOON
;
Gi Beom KIM
;
Bo Sang KWON
;
Jung Min GO
;
Jin Su MOON
;
Eun Jung BAE
;
Chung Il NOH
Author Information
1. Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. eunjbaek@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Alagille syndrome;
Cardiovascular diseases;
Pulmonary valve stenosis;
Cholestasis
- MeSH:
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
- From:Korean Journal of Pediatrics
2015;58(10):392-397
- CountryRepublic of Korea
- Language:English
-
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.
