PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jmedgeneJournal of Medical GeneticsVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
J Med Genet. 1997 February; 34(2): 152–157.
PMCID: PMC1050871

Alagille syndrome.

Abstract

Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal jaundice and cholestasis in older children. In the fully expressed syndrome, affected subjects have intrahepatic bile duct paucity and cholestasis, in conjunction with cardiac malformations (most frequently peripheral pulmonary stenosis), ophthalmological abnormalities (typically of the anterior chamber with posterior embryotoxon being the most common), skeletal anomalies (most commonly butterfly vertebrae), and characteristic facial appearance. Inheritance is autosomal dominant, but expressivity is highly variable. Sibs and parents of probands are often found to have mild expression of the presumptive disease gene, with abnormalities of only one or two systems. The frequency of new mutations appears relatively high, estimated at between 15 and 50%. The disease gene has been mapped to chromosome 20 band p12 based on multiple patients described with cytogenetic or molecular rearrangements of this region. However, the frequency of detectable deletions of 20p12 is low (less than 7%). Progress has been made in the molecular definition of an Alagille syndrome critical region within the short arm of chromosome 20. We will review the clinical, genetic, cytogenetic, and molecular findings in this syndrome.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Watson GH, Miller V. Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child. 1973 Jun;48(6):459–466. [PMC free article] [PubMed]
  • Riely CA, Cotlier E, Jensen PS, Klatskin G. Arteriohepatic dysplasia: a benign syndrome of intrahepatic cholestasis with multiple organ involvement. Ann Intern Med. 1979 Oct;91(4):520–527. [PubMed]
  • Alagille D, Estrada A, Hadchouel M, Gautier M, Odièvre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987 Feb;110(2):195–200. [PubMed]
  • Danks DM, Campbell PE, Jack I, Rogers J, Smith AL. Studies of the aetiology of neonatal hepatitis and biliary atresia. Arch Dis Child. 1977 May;52(5):360–367. [PMC free article] [PubMed]
  • Greenwood RD, Rosenthal A, Crocker AC, Nadas AS. Syndrome of intrahepatic biliary dysgenesis and cardiovascular malformations. Pediatrics. 1976 Aug;58(2):243–247. [PubMed]
  • Henriksen NT, Langmark F, Sorland SJ, Fausa O, Landaas S, Aagenaes O. Hereditary cholestasis combined with peripheral pulmonary stenosis and other anomalies. Acta Paediatr Scand. 1977 Jan;66(1):7–15. [PubMed]
  • Tzakis AG, Reyes J, Tepetes K, Tzoracoleftherakis V, Todo S, Starzl TE. Liver transplantation for Alagille's syndrome. Arch Surg. 1993 Mar;128(3):337–339. [PubMed]
  • Deprettere A, Portmann B, Mowat AP. Syndromic paucity of the intrahepatic bile ducts: diagnostic difficulty; severe morbidity throughout early childhood. J Pediatr Gastroenterol Nutr. 1987 Nov-Dec;6(6):865–871. [PubMed]
  • Novotny NM, Zetterman RK, Antonson DL, Vanderhoof JA. Variation in liver histology in Alagille's syndrome. Am J Gastroenterol. 1981 Jun;75(6):449–450. [PubMed]
  • Silberbach M, Lashley D, Reller MD, Kinn WF, Jr, Terry A, Sunderland CO. Arteriohepatic dysplasia and cardiovascular malformations. Am Heart J. 1994 Mar;127(3):695–699. [PubMed]
  • Mueller RF, Pagon RA, Pepin MG, Haas JE, Kawabori I, Stevenson JG, Stephan MJ, Blumhagen JD, Christie DL. Arteriohepatic dysplasia: phenotypic features and family studies. Clin Genet. 1984 Apr;25(4):323–331. [PubMed]
  • Puklin JE, Riely CA, Simon RM, Cotlier E. Anterior segment and retinal pigmentary abnormalities in arteriohepatic dysplasia. Ophthalmology. 1981 Apr;88(4):337–347. [PubMed]
  • Waring GO, 3rd, Rodrigues MM, Laibson PR. Anterior chamber cleavage syndrome. A stepladder classification. Surv Ophthalmol. 1975 Jul-Aug;20(1):3–27. [PubMed]
  • Wells KK, Pulido JS, Judisch GF, Ossoinig KC, Fisher TC, LaBrecque DR. Ophthalmic features of Alagille syndrome (arteriohepatic dysplasia). J Pediatr Ophthalmol Strabismus. 1993 Mar-Apr;30(2):130–135. [PubMed]
  • Brodsky MC, Cunniff C. Ocular anomalies in the alagille syndrome (arteriohepatic dysplasia). Ophthalmology. 1993 Dec;100(12):1767–1774. [PubMed]
  • Romanchuk KG, Judisch GF, LaBrecque DR. Ocular findings in arteriohepatic dysplasia (Alagille's syndrome). Can J Ophthalmol. 1981 Apr;16(2):94–99. [PubMed]
  • Rosenfield NS, Kelley MJ, Jensen PS, Cotlier E, Rosenfield AT, Riely CA. Arteriohepatic dysplasia: radiologic features of a new syndrome. AJR Am J Roentgenol. 1980 Dec;135(6):1217–1223. [PubMed]
  • Berman MD, Ishak KG, Schaefer EJ, Barnes S, Jones EA. Syndromatic hepatic ductular hypoplasia (arteriohepatic dysplasia): a clinical and hepatic histologic study of three patients. Dig Dis Sci. 1981 Jun;26(6):485–497. [PubMed]
  • Sokol RJ, Heubi JE, Balistreri WF. Intrahepatic "cholestasis facies": is it specific for Alagille syndrome? J Pediatr. 1983 Aug;103(2):205–208. [PubMed]
  • LaBrecque DR, Mitros FA, Nathan RJ, Romanchuk KG, Judisch GF, El-Khoury GH. Four generations of arteriohepatic dysplasia. Hepatology. 1982 Jul-Aug;2(4):467–474. [PubMed]
  • Tolia V, Dubois RS, Watts FB, Jr, Perrin E. Renal abnormalities in paucity of interlobular bile ducts. J Pediatr Gastroenterol Nutr. 1987 Nov-Dec;6(6):971–976. [PubMed]
  • Anad F, Burn J, Matthews D, Cross I, Davison BC, Mueller R, Sands M, Lillington DM, Eastham E. Alagille syndrome and deletion of 20p. J Med Genet. 1990 Dec;27(12):729–737. [PMC free article] [PubMed]
  • Hoffenberg EJ, Narkewicz MR, Sondheimer JM, Smith DJ, Silverman A, Sokol RJ. Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr. 1995 Aug;127(2):220–224. [PubMed]
  • Alagille D, Odièvre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. 1975 Jan;86(1):63–71. [PubMed]
  • Shulman SA, Hyams JS, Gunta R, Greenstein RM, Cassidy SB. Arteriohepatic dysplasia (Alagille syndrome): extreme variability among affected family members. Am J Med Genet. 1984 Oct;19(2):325–332. [PubMed]
  • Dhorne-Pollet S, Deleuze JF, Hadchouel M, Bonaïti-Pellié C. Segregation analysis of Alagille syndrome. J Med Genet. 1994 Jun;31(6):453–457. [PMC free article] [PubMed]
  • Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, Hepner SI, Downing JW. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol. 1985 Jan;121(1):31–36. [PubMed]
  • Elmslie FV, Vivian AJ, Gardiner H, Hall C, Mowat AP, Winter RM. Alagille syndrome: family studies. J Med Genet. 1995 Apr;32(4):264–268. [PMC free article] [PubMed]
  • Byrne JL, Harrod MJ, Friedman JM, Howard-Peebles PN. del(20p) with manifestations of arteriohepatic dysplasia. Am J Med Genet. 1986 Aug;24(4):673–678. [PubMed]
  • Legius E, Fryns JP, Eyskens B, Eggermont E, Desmet V, de Bethune G, Van den Berghe H. Alagille syndrome (arteriohepatic dysplasia) and del(20)(p11.2) Am J Med Genet. 1990 Apr;35(4):532–535. [PubMed]
  • Schnittger S, Höfers C, Heidemann P, Beermann F, Hansmann I. Molecular and cytogenetic analysis of an interstitial 20p deletion associated with syndromic intrahepatic ductular hypoplasia (Alagille syndrome). Hum Genet. 1989 Oct;83(3):239–244. [PubMed]
  • Teebi AS, Murthy DS, Ismail EA, Redha AA. Alagille syndrome with de novo del(20) (p11.2). Am J Med Genet. 1992 Jan 1;42(1):35–38. [PubMed]
  • Spinner NB, Rand EB, Fortina P, Genin A, Taub R, Semeraro A, Piccoli DA. Cytologically balanced t(2;20) in a two-generation family with alagille syndrome: cytogenetic and molecular studies. Am J Hum Genet. 1994 Aug;55(2):238–243. [PubMed]
  • Desmaze C, Deleuze JF, Dutrillaux AM, Thomas G, Hadchouel M, Aurias A. Screening of microdeletions of chromosome 20 in patients with Alagille syndrome. J Med Genet. 1992 Apr;29(4):233–235. [PMC free article] [PubMed]
  • Hol FA, Hamel BC, Geurds MP, Hansmann I, Nabben FA, Daniëls O, Mariman EC. Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three-generation family. Hum Genet. 1995 Jun;95(6):687–690. [PubMed]
  • Rand EB, Spinner NB, Piccoli DA, Whitington PF, Taub R. Molecular analysis of 24 Alagille syndrome families identifies a single submicroscopic deletion and further localizes the Alagille region within 20p12. Am J Hum Genet. 1995 Nov;57(5):1068–1073. [PubMed]
  • Deleuze JF, Hazan J, Dhorne S, Weissenbach J, Hadchouel M. Mapping of microsatellite markers in the Alagille region and screening of microdeletions by genotyping 23 patients. Eur J Hum Genet. 1994;2(3):185–190. [PubMed]
  • Butler MG, Meaney FJ, Palmer CG. Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome. Am J Med Genet. 1986 Mar;23(3):793–809. [PubMed]
  • Driscoll DA, Spinner NB, Budarf ML, McDonald-McGinn DM, Zackai EH, Goldberg RB, Shprintzen RJ, Saal HM, Zonana J, Jones MC, et al. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992 Sep 15;44(2):261–268. [PubMed]
  • Pollet N, Dhorne-Pollet S, Deleuze JF, Boccaccio C, Driancourt C, Raynaud N, Le Paslier D, Hadchouel M, Meunier-Rotival M. Construction of a 3.7-Mb physical map within human chromosome 20p12 ordering 18 markers in the Alagille syndrome locus. Genomics. 1995 Jun 10;27(3):467–474. [PubMed]
  • Dahms BB, Petrelli M, Wyllie R, Henoch MS, Halpin TC, Morrison S, Park MC, Tavill AS. Arteriohepatic dysplasia in infancy and childhood: a longitudinal study of six patients. Hepatology. 1982 May-Jun;2(3):350–358. [PubMed]
  • Levin SE, Zarvos P, Milner S, Schmaman A. Arteriohepatic dysplasia: association of liver disease with pulmonary arterial stenosis as well as facial and skeletal abnormalities. Pediatrics. 1980 Dec;66(6):876–883. [PubMed]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Group