Alagille Syndrome

Author: Ann Scheimann, MD, MBA; Chief Editor: Carmen Cuffari, MD more...

Updated: Feb 7, 2012

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Background
Pathophysiology
Epidemiology
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Background

Alagille syndrome (AS) is an autosomal dominant disorder (OMIM 118450) associated with abnormalities of the liver, heart, skeleton, eye, and kidneys and a characteristic facial appearance.^[1]In 1973, Watson and Miller reported 9 cases of neonatal liver disease with familial pulmonary valvular stenosis.^[2]Then in 1975, Alagille et al described several patients with hypoplasia of the hepatic ducts with associated features.^[3]Typical facial features are shown in the image below.

Typical facial features of Alagille syndrome. Note broad forehead, deep-set eyes and pointed chin.

Pathophysiology

Alagille syndrome is an autosomal dominant disorder with variable expression. Associated abnormalities include those of the liver, heart, eye, skeleton, and kidneys and characteristic facial features. Mild-to-moderate mental retardation also may be present. Mutations in either jagged-1 (JAG1) or notch-2 (NOTCH2) have been reported in patients with Alagille syndrome.^{[4, 5]}The syndrome has been mapped to the 20p12-jagged-1 locus, JAG1, which encodes a ligand critical to the notch gene–signaling cascade that is important in fetal development.^{[6, 5]}Notch signaling has been found to regulate formation of 3-dimensional intrahepatic biliary architecture in murine models.^[7]A minority (6-7%) of patients have complete deletion of JAG1, and approximately 15-50% of mutations are spontaneous.

Frequency

United States

The incidence rate is approximately 1 case in every 100,000 live births.

Mortality/Morbidity

Major contributors to morbidity arise from bile duct paucity or cholestatic liver disease, underlying cardiac disease, CNS vasculopathy, Moyamoya disease, and renal disease.

Sex

No difference in penetrance is reported.

Age

Most children are evaluated when younger than 6 months for either neonatal jaundice (70%), or cardiac murmurs and symptoms (17%). Patients who are less affected, such as family members, are often diagnosed after an index case.

Proceed to Clinical Presentation

Contributor Information and Disclosures

Author

Ann Scheimann, MD, MBA Associate Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution

Ann Scheimann, MD, MBA is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Abbott, Inc Consulting fee Consulting

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven M Schwarz, MD, FAAP, FACN, AGAF Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References

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