Abstract

ALAGILLE SYNDROME BEYOND CHILDHOOD: CLINICAL INSIGHTS AND FUTURE PERSPECTIVES

Tamilselvan S.*, Tamilarasan P., Jothimani

ABSTRACT

Background: Alagille Syndrome (ALGS) is a rare autosomal dominant multisystem disorder primarily caused by mutations in the JAG1 gene (94–95%) and, less commonly, in NOTCH2 (<2%). It affects the liver, heart, eyes, skeleton, kidneys, and facial features. The hallmark liver feature is bile duct paucity, leading to cholestasis, pruritus, and progressive liver disease. Though classified as a pediatric condition, ALGS often extends into adulthood with variable expression and is frequently misdiagnosed due to overlapping symptoms. Aim: This study aims to evaluate current knowledge on ALGS, focusing on its genetic underpinnings, clinical variability, diagnostic complexities, treatment options, and future research directions. Hepatic involvement and advancements in molecular diagnostics and therapies are emphasized. Methods: A bibliometric review was conducted on published literature regarding ALGS. Liver histopathology and geneticdata, especially JAG1 and NOTCH2 mutations, were assessed. Diagnostic criteria, clinical outcomes, and management approaches were analyzed using peer-reviewed sources, highlighting recent pharmacological and surgical advancements. Results: ALGS presents with a broad clinical spectrum, including cholestasis, congenital heart defects (e.g., pulmonary artery stenosis, Tetralogy of Fallot), butterfly vertebrae, ocular anomalies, and distinctive facial features. Around 15–30% of patients with liver involvement progress to end-stage disease requiring liver transplantation. Therapies such as Maralixibat and Odevixibat reduce pruritus effectively. Emerging strategies include gene editing and patient-derived organoids. With multidisciplinary care, survival into adulthood exceeds 90%, though quality of life may be affected. Conclusion: ALGS demands early diagnosis, genetic confirmation, and ongoing multidisciplinary management. Gene-targeted therapies hold promise for more definitive treatments in the future.

Keywords: Alagille syndrome, JAG1 Mutation, Multisystem Disorder, Gene-Targeted Therapy.