Extensive Clinical Examination of Alagille Syndrome, Genetic Pathways, and Evolving Therapeutic Approaches
Alagille syndrome is a rare genetic disorder affecting the liver, heart, kidneys, eyes, and skeletal system. It is caused primarily by mutations in the JAG1 or NOTCH2 genes, disrupting the Notch signaling pathway responsible for organ development and cellular differentiation.
The condition is characterized by bile duct paucity, leading to chronic cholestasis, jaundice, malabsorption of nutrients, and growth delays. Heart defects—particularly pulmonary artery stenosis—are common, alongside distinct facial features, vertebral anomalies, and ocular abnormalities.
Diagnosis relies on genetic testing, liver biopsy, imaging studies, and clinical evaluation. Because symptoms vary widely, some individuals present mild manifestations, while others experience severe organ complications.
Management focuses on symptom control. Bile flow improvement therapies, nutritional supplementation, fat-soluble vitamin support, and antipruritic medications help maintain quality of life. In severe cases, liver transplantation may be necessary.
Research into molecular mechanisms is expanding treatment possibilities. Targeted therapies aiming to modulate Notch signaling, gene-based strategies, and regenerative…