Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center

  • Ahn, Kyung Jin (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Yoon, Ja Kyoung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kim, Gi Beom (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kwon, Bo Sang (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Go, Jung Min (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Moon, Jin Su (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Bae, Eun Jung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Noh, Chung Il (Department of Pediatrics, Seoul National University Children's Hospital)
  • 투고 : 2014.07.29
  • 심사 : 2014.11.04
  • 발행 : 2015.10.15
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초록

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.

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참고문헌

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  2. Sherloc: a comprehensive refinement of the ACMG–AMP variant classification criteria vol.19, pp.10, 2015, https://doi.org/10.1038/gim.2017.37
  3. Direct Hyperbilirubinemia in an Infant vol.56, pp.7, 2017, https://doi.org/10.1177/0009922816664166
  4. A Novel c.91dupG JAG1 Gene Mutation Is Associated with Early Onset and Severe Alagille Syndrome vol.2018, pp.None, 2018, https://doi.org/10.1155/2018/1369413
  5. Alagille Syndrome: A Novel Mutation in JAG1 Gene vol.7, pp.None, 2015, https://doi.org/10.3389/fped.2019.00199
  6. A practical approach to the pathology of neonatal cholestatic liver disease vol.36, pp.6, 2015, https://doi.org/10.1053/j.semdp.2019.07.004
  7. Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease vol.229, pp.None, 2021, https://doi.org/10.1016/j.jpeds.2020.09.053