Renal anomalies in Alagille syndrome: A disease-defining feature§

Authors

  • Binita M. Kamath,

    Corresponding author
    1. Division of Gastroenterology, Hepatology and Nutrition at The Hospital for Sick Children, Toronto, Ontario, Canada
    2. Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
    • Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8.
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  • Gisele Podkameni,

    1. Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Anne L. Hutchinson,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Laura D. Leonard,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Jennifer Gerfen,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Ian D. Krantz,

    1. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    3. The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • David A. Piccoli,

    1. Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Nancy B. Spinner,

    1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Kathleen M. Loomes,

    1. Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania
    2. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Kevin Meyers

    1. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
    2. Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • How to Cite this Article: Kamath BM, Podkameni G, Hutchinson AL, Leonard LD, Gerfen J, Krantz ID, Piccoli DA, Spinner NB, Loomes KM, Meyers K. 2012. Renal anomalies in Alagille syndrome: A disease-defining feature. Am J Med Genet Part A 158A:85–89.

  • Disclosures: The authors report no financial disclosures or conflicts of interest.

  • §

    Dr. Loomes and Dr. Meyers declare joint responsibility for senior authorship.

Abstract

Alagille syndrome (ALGS) is an autosomal dominant condition, primarily caused by mutations in JAGGED1. ALGS is defined by cholestatic liver disease, cardiac disease and involvement of the face, skeleton, and eyes with variable expression of these features. Renal involvement has been reported though not formally described. The objective of this study was to systematically characterize the renal involvement in ALGS. We performed a retrospective review of 466 JAGGED1 mutation-positive ALGS patients. Charts were reviewed for serum biochemistries, renal ultrasounds or other imaging, urinalysis, and clinical reports from pediatric nephrologists. The clinical data were reviewed by two pediatric hepatologists and a pediatric nephrologist. Of 466 charts reviewed we found 187 yielded evaluable renal information. Of these, 73/187 were shown to have renal involvement, representing 39% of the study cohort. Renal dysplasia was the most common anomaly seen. Genotype analysis of the JAGGED1 mutations in the patients with and without renal involvement did not reveal an association with mutation type. From the study we concluded that renal involvement has a prevalence of 39% in ALGS in our evaluable patients. Renal dysplasia is the most common renal anomaly. This finding correlates with the known role of the Notch pathway in glomerular development. Since renal disease of the type seen in ALGS can impair growth and impact liver transplantation, there is a clear need for a prospective study of renal involvement in ALGS and the development of guidelines for evaluation and management. These data also suggest that renal involvement be considered the sixth defining criterion for ALGS. © 2011 Wiley Periodicals, Inc.

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