factors that can result in gene mutations may include radiation such as ultraviolet rays from the sun, or chemicals such as benzene, which is found in cigarette smoke. These cases occur in people with no familial history of the disorder. Pathophysiology JAG1 and NOTCH2 encode for proteins that are crucial to the notch gene–signaling cascade. Specifically, JAG1 encodes for a surface-binding ligand that regulates the notch signaling pathway. It plays a crucial role in cell signaling during embryonic development. If the pathway is disrupted due to mutations, an infant will not develop properly. Alagille syndrome causes bile duct paucity, which is characterized by narrow and malformed bile ducts. Bile duct paucity causes bile to build up in the liver, resulting in scarring of the liver which hinders the liver's normal functions, like blood filtration and drug metabolism. The notch gene–signaling cascade is also important for cell–cell recognition, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life, and is specially important for: Atrioventricular (AV) canal development Ventricular development Ventricle (heart) outflow tract development Angiogenesis Pancreatic development Intestinal development Bone development Respiratory system development Neuron cell differentiation Neurite development Gliogenesis Adult brain function Diagnosis Alagille syndrome can be extremely difficult to diagnose. While people are born with ALGS, it is almost always diagnosed later during childhood. The diagnosis can be difficult because the severity of the disease varies widely among patients. Some common clinical tests that are run in order to diagnose the disease include vertebral x-rays, heart exams to detect any defects such as a heart murmur, and a liver biopsy to detect liver disease or any precursors. If a patient presents with multiple symptoms such as jaundice, heart murmur, and the characteristic facial features discussed above (deep set eyes, broad brow, etc.), they are likely to be diagnosed with Alagille syndrome. A more calculated and specific diagnosis can be done with genetic testing. Next-generation sequencing can be utilized to detect single nucleotide polymorphisms (SNPs) in the affected gene(s). Multiplex ligation-dependent probe amplification (MLPA) can detect large deletions and/or insertions and microarray comparative genomic hybridization is used to improve the accuracy of MLPA. Treatment Early treatment is possible once the disease is diagnosed. Treatments of Alagille syndrome typically involve medications, therapies, and/or surgical procedures. All treatments aim to improve bile excretion from the liver, reduce pain caused by the disease, and help improve nutritional