Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment

Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in or , which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occu...

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Bibliographic Details
Published inSeminars in liver disease Vol. 41; no. 4; p. 525
Main Authors Kohut, Taisa J, Gilbert, Melissa A, Loomes, Kathleen M
Format Journal Article
LanguageEnglish
Published United States 01.11.2021
Subjects
Alagille Syndrome - diagnosis
Alagille Syndrome - genetics
Alagille Syndrome - therapy
Humans
Jagged-1 Protein - genetics
Jagged-1 Protein - metabolism
Mutation
Receptor, Notch2
Signal Transduction
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Summary:Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in or , which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occur with variable phenotypic penetrance. Genotype-phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity, and it has been hypothesized that modifier genes may modulate the effects of and pathogenic variants. Medical management is supportive, focusing on clinical manifestations of disease, with liver transplant indicated for severe pruritus, liver synthetic dysfunction, portal hypertension, bone fractures, and/or growth failure. New therapeutic approaches are under investigation, including ileal bile acid transporter (IBAT) inhibitors and other approaches that may involve targeted interventions to augment the Notch signaling pathway in involved tissues.
ISSN:1098-8971
DOI:10.1055/s-0041-1730951