IllnessAlagille syndrome, differential diagnosis

NGS +

The pathogenesis in Alagille syndrome involves the liver, heart and other parts of the body. Main features are abnormalities in the bile ducts, causing bile to back up in the liver and scarring with jaundice, pruritus and xanthomas. Cardiac problems include pulmonary stenosis with ventricular septal defect and other abnormalities such as tetralogy of Fallot. Characteristic facial features involve a broad, prominent forehead, deep-set eyes and a small, pointed chin. In addition, the central nervous system and kidneys may be affected as well as the vertebrae. The first problems usually become apparent in infancy or early childhood. The severity of the disorder varies among affected individuals, even within a family. Symptoms range from being so mild that they go unnoticed to severe heart and/or liver disease requiring transplantation. Rarely, only isolated heart defects or a characteristic face are observed. The mode of inheritance is autosomal dominant. JAG1 mutations are identified in >90% of patients, and NOTCH2 mutations are present in a few others. Since overall the aforementioned mutations are detected in about 97% of Alagille patients, the clinical diagnosis is not confirmed by molecular genetics in virtually all cases.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1273/

• Alias: Alagille-Watson syndrome
• Alias: Arteriohepatic dysplasia
• Alias: Cholestasis with peripheral pulmonary stenosis
• Alias: Hepatic ductular hypoplasia, syndromatic
• Allelic: Anterior segment dysgenesis 3, multiple subtypes (FOXC1)
• Allelic: Anterior segment dysgenesis 4 (PITX2)
• Allelic: Axenfeld-Rieger syndrome, type 1 (PITX2)
• Allelic: Axenfeld-Rieger syndrome, type 3 (FOXC1)
• Allelic: Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Allelic: Congenital heart defects, multiple types, 6 (GDF1)
• Allelic: Cutis laxa, AD (ELN)
• Allelic: Deafness, congenital heart defects + posterior embryotoxon (JAG1)
• Allelic: Emphysema due to AAT deficiency (SERPINA1)
• Allelic: Gallbladder disease 1 (ABCB4)
• Allelic: Hajdu-Cheney syndrome (NOTCH2)
• Allelic: Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
• Allelic: Melorheostosis, isolated, somatic mosaic (MAP2K1)
• Allelic: Nephronophthisis 9 (NEK8)
• Allelic: Pancreatitis, hereditary (CFTR)
• Allelic: Right atrial isomerism [Ivemark] (GDF1)
• Allelic: Supravalvar aortic stenosis (ELN)
• Allelic: Tetralogy of Fallot (JAG1)
• Alagille syndrome 1 (JAG1)
• Alagille syndrome 2 (NOTCH2)
• Alpha-methylacyl-CoA racemase deficiency (AMACR)
• Bile acid synthesis defect, congenital, 4 (AMACR)
• Cholestasis, benign recurrent intrahepatic (ATP8B1)
• Cholestasis, benign recurrent intrahepatic, 2 (ABCB11)
• Cholestasis, intrahepatic, of pregnancy, 1 (ATP8B1)
• Cholestasis, intrahepatic, of pregnancy, 3 (ABCB4)
• Cholestasis, progressive familial intrahepatic 1 (ATP8B1)
• Cholestasis, progressive familial intrahepatic 2 (ABCB11)
• Cystic fibrosis (CFTR)
• Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
• Galactosemia (GALT)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Noonan syndrome 1 (PTPN11)
• Noonan syndrome 4 (SOS1)
• Noonan syndrome 5 (RAF1)
• Noonan syndrome 7 (BRAF)
• Noonan syndrome 8 (RIT1)
• Peroxisome biogenesis disorder 1A [Zellweger] (PEX1)
• Peroxisome biogenesis disorder 1B [NALD/IRD] (PEX1)
• Peroxisome biogenesis disorder 3A [Zellweger] (PEX12)
• Peroxisome biogenesis disorder 3B (PEX12)
• Peroxisome biogenesis disorder 4A [Zellweger] (PEX6)
• Peroxisome biogenesis disorder 4B (PEX6)
• Renal-hepatic-pancreatic dysplasia 2 (NEK8)
• Watson syndrome (NF1)
• Williams-Beuren syndrome (ELN)