Abstract Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is an autosomal dominant disease with multisystem involvement. In this disease, the Notch signalling pathway is impaired due to mutation in JAG1 (ALGStype 1) or NOTCH2 (ALGS type 2) gene, affecting multiple organs or systems such as liver, heart, eyes, vertebrateand face. The main clinical features of ALGS include chronic cholestasis, congenital heart disease, mild vertebralsegmentation abnormalities, characteristic face, postcorneal embryotoxon and poor kidney development. This article reviews the recent advances in the pathogenesis, clinical presentations, diagnosis and treatment of this syndrome.
Ciocca M, Alvarez F. Alagille syndrome[J]. Arch Argent Pediatr, 2012, 110(6):509-515.
[2]
Kamath BM, Yin W, Miller H, et al. Outcomes of liver transplantation for patients with Alagille syndrome:the studies of pediatric liver transplantation experience[J]. Liver Transpl, 2012, 18(8):940-948.
[3]
Leonard LD, Chao G, Baker A, et al. Clinical utility gene card for:Alagille syndrome (ALGS)[J]. Eur J Hum Genet, 2014, 22(3):e1-e4.
[4]
Vozzi D, Licastro D, Martelossi S, et al. Alagille syndrome:a new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA[J]. Mol Syndromol, 2013, 4(4):207-210.
[5]
Vanorny DA, Prasasya RD, Chalpe AJ, et al. Notch signaling regulates ovarian follicle formation and coordinates follicular growth[J]. Mol Endocrinol, 2014, 28(4):499-511.
[6]
Zhou XL, Liu JC. Role of Notch signaling in the mammalian heart[J]. Braz J Med Biol Res, 2014, 47(1):1-10.
[7]
Lin HC, Le Hoang P, Hutchinson A, et al. Alagille syndrome in a Vietnamese cohort:mutation analysis and assessment of facial features[J]. Am J Med Genet A, 2012, 158A(5):1005-1013.
[8]
McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway[J]. Am J Hum Genet, 2006, 79(1):169-173.
[9]
Kamath BM, Spinner NB, Rosenblum ND. Renal involvement and the role of Notch signalling in Alagille syndrome[J]. Nat Rev Nephrol, 2013, 9(7):409-418.
[10]
Kamath BM, Bauer RC, Loomes KM, et al. NOTCH2 mutations in Alagille syndrome[J]. J Med Genet, 2012, 49(2):138-144.
[11]
Sparks EE, Huppert KA, Brown MA, et al. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice[J]. Hepatology, 2010, 51(4):1391-1400.
[12]
Sparks EE, Perrien DS, Huppert KA, et al. Defects in hepatic Notch signaling result in disruption of the communicating intrahepatic bile duct network in mice[J]. Dis Model Mech, 2011, 4(3):359-367.
[13]
Penton AL, Leonard LD, Spinner NB. Notch signaling in human development and disease[J]. Semin Cell Dev Biol, 2012, 23(4):450-457.
[14]
Hofmann JJ, Briot A, Enciso J, et al. Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome[J]. Development, 2012, 139(23):4449-4460.
[15]
Zanotti S, Canalis E. Notch regulation of bone development and remodeling and related skeletal disorders[J]. Calcif Tissue Int, 2012, 90(2):69-75.
[16]
Sirin Y, Susztak K. Notch in the kidney:development and disease[J]. J Pathol, 2012, 226(2):394-403.
[17]
Benoit G, Sartelet H, Levy E, et al. Mesangiolipidosis in Alagille syndrome-relationship with apolipoprotein A-I[J]. Nephrol Dial Transplant, 2007, 22(7):2072-2075.
[18]
Humphreys R, Zheng W, Prince LS, et al. Cranial neural crest ablation of Jagged1 recapitulates the craniofacial phenotype of Alagille syndrome patients[J]. Hum Mol Genet, 2012, 21(6):1374-1383.
[19]
Yilmaz S, Turhan T, Mutluer S, et al. The association of Alagille syndrome and craniosynostosis[J]. Pediatr Neurol, 2013, 48(2):146-148.
[20]
Srivastava A, Goel D, Bolia R, et al. Alagille syndrome:experience of a tertiary care center in North India[J]. Indian J Gastroenterol, 2014, 33(1):59-62.
[21]
Vajro P, Ferrante L, Paolella G. Alagille syndrome:an overview[J]. Clin Res Hepatol Gastroenterol, 2012, 36(3):275-277.
[22]
Kamath BM, Munoz PS, Bab N, et al. A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2010, 50(5):526-530.
[23]
Wang JS, Wang XH, Zhu QR, et al. Clinical and pathological characteristics of Alagille syndrome in Chinese children[J]. World J Pediatr, 2008, 4(4):283-288.
Bales CB, Kamath BM, Munoz PS, et al. Pathologic lower extremity fractures in children with Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2010, 51(1):66-70.
[25]
Kamath BM, Loomes KM, Oakey RJ, et al. Facial features in Alagille syndrome:specific or cholestasis facies? [J]. Am J Med Genet, 2002, 112(2):163-170.
[26]
Mozhgan Z, Bita G, Mahmood H, et al. Paucity of intrahepatic bile ducts in neonates:the first case series from iran[J]. Iran J Pediatr, 2013, 23(1):65-70.
[27]
Makino S, Ohkubo Y, Tampo H. Optical coherence tomography and fundus autofluorescence imaging study of chorioretinal atrophy involving the macula in Alagille syndrome[J]. Clin Ophthalmol, 2012, 6:1445-1448.
[28]
Kamath BM, Piccoli DA, Magee JC, et al. Pancreatic insufficiency is not a prevalent problem in Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2012, 55(5):612-614. 29] Fouillade C, Monet-Leprêtre M, Baron-Menguy C, et al. Notch signalling in smooth muscle cells during development and disease[J]. Cardiovasc Res, 2012, 95(2):138-146.
[30]
Olczak-Kowalczyk D, Pawłowska J, Kowalczyk W. Oral health status in children with chronic liver disease[J]. J Stoma, 2011, 64(10):760-774.
[31]
Berniczei-Royko A, Chałas R, Mitura I, et al. Medical and dental management of Alagille syndrome:A review[J]. Med Sci Monit, 2014, 20:476-480.
[32]
Alagille D, Estrada A, Hadchouel M, et al. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia):review of 80 cases[J]. J Pediatr, 1987, 110(2):195-200.
[33]
Salem JE, Bruguiere E, Iserin L, et al. Hypertension and aortorenal disease in Alagille syndrome[J]. J Hypertens, 2012, 30(7):1300-1306.
[34]
Olsen IE, Ittenbach RF, Rovner AJ, et al. Deficits in sizeadjusted bone mass in children with Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2005, 40(1):76-82.
[35]
Kamath BM, Bason L, Piccoli DA, et al. Consequences of JAG1 mutations[J]. J Med Genet, 2003, 40(12):891-895.
[36]
McElhinney DB, Krantz ID, Bason L, et al. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome[J]. Circulation, 2002, 106(20):2567-2574.
[37]
Witt H, Neumann LM, Grollmuss O, et al. Prenatal diagnosis of Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2004, 38(1):105-106.
[38]
Kamath BM. Alagille syndrome[M]//Suchy FJ, Sokal RJ, Balistreri WF, et al. Liver Disease in Children.3rd ed. New York:Cambridge University Press, 2007:326-345.
[39]
Guru Murthy GS, Rana BS, Das A, et al. Alagille syndrome:a rare disease in an adolescent[J]. Dig Dis Sci, 2012, 57(11):3035-3057.
[40]
Turnpenny PD, Ellard S. Alagille syndrome:pathogenesis, diagnosis and management[J]. Eur J Hum Genet, 2012, 20(3):251-257.
[41]
Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome[J]. J Pediatr Gastroenterol Nutr, 2010, 50(6):580-586.
[42]
Moisseiev E, Cohen S, Dotan G. Alagille syndrome associated with xerophthalmia[J]. Case Rep Ophthalmol, 2013, 4(3):311-315.
[43]
Tapia Ceballos L, Picazo Angelín B, Ruiz García C. Use of statins in children[J]. An Pediatr (Barc), 2008, 68(4):385-392.
[44]
Fukumoto M, Ikeda T, Sugiyama T, et al. A case of Alagille syndrome complicated by intraocular lens subluxation and rhegmatogenous retinal detachment[J]. Clin Ophthalmol, 2013, 7:1463-1465.
[45]
Shrivastava R, Williams A, Mikhail A, et al. An unusual cause of hypertension and renal failure:a case series of a family with Alagille syndrome[J]. Nephrol Dial Transplant, 2010, 25(5):1501-1506.
[46]
Mozer-Glassberg Y, Hojsak I, Zevit N, et al. Pruritus responsive to naltrexone in a patient with cholestatic liver disease[J]. Isr Med Assoc J, 2011, 13(2):111-112.
[47]
Kamath BM, Yin W, Miller H, et al. Outcomes of liver transplantation for patients with Alagille syndrome:the studies of pediatric liver transplantation experience[J]. Liver Transpl, 2012, 18(8):940-948.
[48]
Lee CN, Tiao MM, Chen HJ, et al. Characteristics and outcome of liver transplantation in children with Alagille syndrome:a singlecenter experience[J]. Pediatr Neonatol, 2014, 55(2):135-138.
[49]
Cunningham JW, McElhinney DB, Gauvreau K, et al. Outcomes after primary transcatheter therapy in infants and young children with severe bilateral peripheral pulmonary artery stenosis[J]. Circ Cardiovasc Interv, 2013, 6(4):460-467.
[50]
Mainwaring RD, Sheikh AY, Punn R, et al. Surgical outcomes for patients with pulmonary atresia/major aortopulmonary collaterals and Alagille syndrome[J]. Eur J Cardiothorac Surg, 2012, 42(2):235-240.
[51]
Monge MC, Mainwaring RD, Sheikh AY, et al. Surgical reconstruction of peripheral pulmonary artery stenosis in Williams and Alagille syndromes[J]. J Thorac Cardiovasc Surg, 2013, 145(2):476-481.
