Jianguo Yan, Yuanzhi Huang, Lili Cao, Yi Dong, Zhiqiang Xu, Fuchuan Wang, Yinjie Gao, Danni Feng, Min Zhang
{"title":"Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome.","authors":"Jianguo Yan, Yuanzhi Huang, Lili Cao, Yi Dong, Zhiqiang Xu, Fuchuan Wang, Yinjie Gao, Danni Feng, Min Zhang","doi":"10.1186/s12887-024-04973-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022.</p><p><strong>Results: </strong>The clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period.</p><p><strong>Conclusions: </strong>Among children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.</p>","PeriodicalId":9144,"journal":{"name":"BMC Pediatrics","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334458/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12887-024-04973-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Alagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis.
Methods: We retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022.
Results: The clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period.
Conclusions: Among children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.
期刊介绍:
BMC Pediatrics is an open access journal publishing peer-reviewed research articles in all aspects of health care in neonates, children and adolescents, as well as related molecular genetics, pathophysiology, and epidemiology.