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Ocular Manifestations of Gastrointestinal Disease

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The Eye in Pediatric Systemic Disease

Abstract

Many pediatric gastrointestinal disorders have ophthalmic manifestations. The detection of these ophthalmic features may help establish the underlying diagnosis. Pediatric liver, intestinal and pancreatic diseases with ophthalmic manifestations are discussed with extensive review of the relevant literature. Where relevant the pathologic mechanisms underlying these manifestations are discussed.

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References

  1. Miethke AG, Balistreri WF. Approach to neonatal cholestasis. In: Kleinman R, Goulet O, Miele-Vergani G, Sanderson I, Sherman P, Shneider B, editors. Walker’s pediatric gastrointestinal disease, vol. 2. 5th ed. Hamilton: BC Becker; 2008. p. 791.

    Google Scholar 

  2. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012;20(3):251–7.

    Article  CAS  PubMed  Google Scholar 

  3. Alagille D, Estrada A, Hadchouel M, Gautler M, Odièvre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987;110(2):195–200.

    Article  CAS  PubMed  Google Scholar 

  4. 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;86(1):63–71.

    Article  CAS  PubMed  Google Scholar 

  5. Watson GH, Miller V. Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child. 1973;48(6):459–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kamath BM, Bauer RC, Loomes KM, Chao G, Gerfen J, Hutchinson A, et al. NOTCH2 mutations in Alagille syndrome. J Med Genet. 2012;49(2):138–44.

    Article  CAS  PubMed  Google Scholar 

  7. Hansen TW. Pioneers in the scientific study of neonatal jaundice and kernicterus. Pediatrics. 2000;106(2), E15.

    Article  CAS  PubMed  Google Scholar 

  8. Mowat AP. Biliary atresia into the 21st century: a historical perspective. Hepatology. 1996;23(6):1693–5.

    Article  CAS  PubMed  Google Scholar 

  9. Riely CA, Cotlier E, Jensen PS, Klatskin G. Arteriohepatic dysplasia: a benign syndrome of intrahepatic cholestasis with multiple organ involvement. Ann Intern Med. 1979;91(4):520–7.

    Article  CAS  PubMed  Google Scholar 

  10. Baird LC, Smith ER, Ichord R, Piccoli DA, Bernard TJ, Spinner NB, et al. Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization. J Pediatr. 2015;166(2):470–3.

    Article  PubMed  Google Scholar 

  11. Bidaguren A, Blanco A, Gibelalde A, Irigoyen C. Progressive geographic chorioretinopathy associated with Alagille syndrome. Arch Soc Esp Oftalmol. 2007;82(8):513–15.

    Article  CAS  PubMed  Google Scholar 

  12. Brodsky MC, Cunniff C. Ocular anomalies in the alagille syndrome (arteriohepatic dysplasia). Ophthalmology. 1993;100(12):1767–74.

    Article  CAS  PubMed  Google Scholar 

  13. Fea A, Grosso A, Rabbione M, Grignolo F. Alagille syndrome and optic pit. Graefes Arch Clin Exp Ophthalmol. 2007;245(2):315–17.

    Article  PubMed  Google Scholar 

  14. Fukumoto M, Ikeda T, Sugiyama T, Ueki M, Sato T, Ishizaki E. A case of Alagille syndrome complicated by intraocular lens subluxation and rhegmatogenous retinal detachment. Clin Ophthalmol. 2013;7:1463–5.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, et al. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999;106(2):330–7.

    Article  CAS  PubMed  Google Scholar 

  16. Kamoun R, Mili Boussen I, Beltaief O, Ouertani A. Drusen in children: three case studies. J Fr Ophtalmol. 2008;31(1), e1.

    Article  CAS  PubMed  Google Scholar 

  17. Lebuisson DA, Herbet-Frileux F, Aron JJ, Odievre M, Alagille D, Cotlier E. Ocular manifestations accompanying congenital biliary duct hypoplasia. Bull Soc Ophtalmol Fr. 1981;81(2):169–70.

    CAS  PubMed  Google Scholar 

  18. Moisseiev E, Cohen S, Dotan G. Alagille syndrome associated with xerophthalmia. Case Rep Ophthalmol. 2013;4(3):311–15.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mouzaki M, Nichter C, Qureshi M, Rountree B, Furuya KN. Idiopathic intracranial hypertension in two patients with Alagille syndrome. J Child Neurol. 2010;25(8):1006–8.

    Article  PubMed  Google Scholar 

  20. Narula P, Gifford J, Steggall MA, Lloyd C, Van Mourik ID, McKiernan PJ, et al. Visual loss and idiopathic intracranial hypertension in children with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2006;43(3):348–52.

    Article  PubMed  Google Scholar 

  21. Nischal KK, Hingorani M, Bentley CR, Vivian AJ, Bird AC, Baker AJ, et al. Ocular ultrasound in Alagille syndrome: a new sign. Ophthalmology. 1997;104(1):79–85.

    Article  CAS  PubMed  Google Scholar 

  22. Puklin JE, Riely CA, Simon RM, Cotlier E. Anterior segment and retinal pigmentary abnormalities in arteriohepatic dysplasia. Ophthalmology. 1981;88(4):337–47.

    Article  CAS  PubMed  Google Scholar 

  23. Ricci B, Lepore D, Iossa M, Santo A, Chiaretti A. Ocular anomalies in Alagille’s syndrome. J Fr Ophtalmol. 1991;14(8–9):481–5.

    CAS  PubMed  Google Scholar 

  24. Rocha R, Soro I, Leitao A, Silva ML, Leao M. Moyamoya vascular pattern in Alagille syndrome. Pediatr Neurol. 2012;47(2):125–8.

    Article  PubMed  Google Scholar 

  25. Romanchuk KG, Judisch GF, LaBrecque DR. Ocular findings in arteriohepatic dysplasia (Alagille’s syndrome). Can J Ophthalmol. 1981;16(2):94–9.

    CAS  PubMed  Google Scholar 

  26. Tanino T, Ishihara A, Naganuma K, Nakahata T. Electrophysiological findings in a family with congenital arteriohepatic dysplasia (Alagille syndrome). Doc Ophthalmol. 1986;63(1):83–9.

    Article  CAS  PubMed  Google Scholar 

  27. Voykov B, Guenova E, Sturm E, Deuter C. Alagille syndrome associated with myelinated retinal nerve fibers. Ophthalmologica. 2009;223(5):348–50.

    Article  PubMed  Google Scholar 

  28. Wells KK, Pulido JS, Judisch GF, Ossoinig KC, Fisher TC, LaBrecque DR. Ophthalmic features of Alagille syndrome (arteriohepatic dysplasia). J Pediatr Ophthalmol Strabismus. 1993;30(2):130–5.

    CAS  PubMed  Google Scholar 

  29. Danks DM, Campbell PE, Jack I, Rogers J, Smith AL. Studies of the aetiology of neonatal hepatitis and biliary atresia. Arch Dis Child. 1977;52(5):360–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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;6(6):865–71.

    Article  CAS  PubMed  Google Scholar 

  31. Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology. 1999;29(3):822–9.

    Article  CAS  PubMed  Google Scholar 

  32. 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;127(2):220–4.

    Article  CAS  PubMed  Google Scholar 

  33. Quiros-Tejeira RE, Ament ME, Heyman MB, Martin MG, Rosenthal P, Hall TR, et al. Variable morbidity in alagille syndrome: a review of 43 cases. J Pediatr Gastroenterol Nutr. 1999;29(4):431–7.

    Article  CAS  PubMed  Google Scholar 

  34. Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, et al. Diagnosis of Alagille syndrome-25 years of experience at King’s College Hospital. J Pediatr Gastroenterol Nutr. 2011;52(1):84–9.

    Article  CAS  PubMed  Google Scholar 

  35. Guegan K, Stals K, Day M, Turnpenny P, Ellard S. JAG1 mutations are found in approximately one third of patients presenting with only one or two clinical features of Alagille syndrome. Clin Genet. 2012;82(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  36. Kamath BM, Spinner NB, Rosenblum ND. Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol. 2013;9(7):409–18.

    Article  CAS  PubMed  Google Scholar 

  37. McElhinney DB, Krantz ID, Bason L, Piccoli DA, Emerick KM, Spinner NB, et al. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome. Circulation. 2002;106(20):2567–74.

    Article  PubMed  Google Scholar 

  38. Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, et al. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109(11):1354–8.

    Article  PubMed  Google Scholar 

  39. Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB. Consequences of JAG1 mutations. J Med Genet. 2003;40(12):891–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Krantz ID, Smith R, Colliton RP, Tinkel H, Zackai EH, Piccoli DA, et al. Jagged1 mutations in patients ascertained with isolated congenital heart defects. Am J Med Genet. 1999;84(1):56–60.

    Article  CAS  PubMed  Google Scholar 

  41. Robert ML, Lopez T, Crolla J, Huang S, Owen C, Burvill-Holmes L, et al. Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart. Clin Dysmorphol. 2007;16(4):241–6.

    Article  PubMed  Google Scholar 

  42. Sanderson E, Newman V, Haigh SF, Baker A, Sidhu PS. Vertebral anomalies in children with Alagille syndrome: an analysis of 50 consecutive patients. Pediatr Radiol. 2002;32(2):114–19.

    Article  PubMed  Google Scholar 

  43. Turnpenny PD, Alman B, Cornier AS, Giampietro PF, Offiah A, Tassy O, et al. Abnormal vertebral segmentation and the notch signaling pathway in man. Dev Dyn. 2007;236(6):1456–74.

    Article  CAS  PubMed  Google Scholar 

  44. Berrocal T, Gamo E, Navalon J, Prieto C, Al-Assir I, Cortes P, et al. Syndrome of Alagille: radiological and sonographic findings. A review of 37 cases. Eur Radiol. 1997;7(1):115–18.

    Article  CAS  PubMed  Google Scholar 

  45. Greenwood RD, Rosenthal A, Crocker AC, Nadas AS. Syndrome of intrahepatic biliary dysgenesis and cardiovascular malformations. Pediatrics. 1976;58(2):243–7.

    CAS  PubMed  Google Scholar 

  46. Kamath BM, Stolle C, Bason L, Colliton RP, Piccoli DA, Spinner NB, et al. Craniosynostosis in Alagille syndrome. Am J Med Genet. 2002;112(2):176–80.

    Article  PubMed  Google Scholar 

  47. Yilmaz S, Turhan T, Mutluer S, Aydogdu S. The association of Alagille syndrome and craniosynostosis. Pediatr Neurol. 2013;48(2):146–8.

    Article  PubMed  Google Scholar 

  48. Yen HY, Ting MC, Maxson RE. Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells. Dev Biol. 2010;347(2):258–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ryan RS, Myckatyn SO, Reid GD, Munk P. Alagille syndrome: case report with bilateral radio-ulnar synostosis and a literature review. Skelet Radiol. 2003;32(8):489–91.

    Article  CAS  Google Scholar 

  50. Kamath BM, Loomes KM, Oakey RJ, Krantz ID. Supernumerary digital flexion creases: an additional clinical manifestation of Alagille syndrome. Am J Med Genet. 2002;112(2):171–5.

    PubMed  Google Scholar 

  51. Bales CB, Kamath BM, Munoz PS, Nguyen A, Piccoli DA, Spinner NB, et al. Pathologic lower extremity fractures in children with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51(1):66–70.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Olsen IE, Ittenbach RF, Rovner AJ, Leonard MB, Mulberg AE, Stallings VA, et al. Deficits in size-adjusted bone mass in children with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2005;40(1):76–82.

    Article  PubMed  Google Scholar 

  53. Krantz ID, Piccoli DA, Spinner NB. Clinical and molecular genetics of Alagille syndrome. Curr Opin Pediatr. 1999;11(6):558–64.

    Article  CAS  PubMed  Google Scholar 

  54. Sokol RJ, Heubi JE, Balistreri WF. Intrahepatic “cholestasis facies”: is it specific for Alagille syndrome? J Pediatr. 1983;103(2):205–8.

    Article  CAS  PubMed  Google Scholar 

  55. Kamath BM, Loomes KM, Oakey RJ, Emerick KE, Conversano T, Spinner NB, et al. Facial features in Alagille syndrome: specific or cholestasis facies? Am J Med Genet. 2002;112(2):163–70.

    Article  PubMed  Google Scholar 

  56. Woolfenden AR, Albers GW, Steinberg GK, Hahn JS, Johnston DCC, Farrell K. Moyamoya syndrome in children with Alagille syndrome: additional evidence of a vasculopathy. Pediatrics. 1999;103(2):505–8.

    Article  CAS  PubMed  Google Scholar 

  57. Connor SE, Hewes D, Ball C, Jarosz JM. Alagille syndrome associated with angiographic moyamoya. Childs Nerv Syst. 2002;18(3–4):186–90.

    Article  CAS  PubMed  Google Scholar 

  58. Jacobson DM, Berg R, Wall M, Digre KB, Corbett JJ, Ellefson RD. Serum vitamin A concentration is elevated in idiopathic intracranial hypertension. Neurology. 1999;53(5):1114–18.

    Article  CAS  PubMed  Google Scholar 

  59. Chong SK, Lindridge J, Moniz C, Mowat AP. Exocrine pancreatic insufficiency in syndromic paucity of interlobular bile ducts. J Pediatr Gastroenterol Nutr. 1989;9(4):445–9.

    Article  CAS  PubMed  Google Scholar 

  60. Devriendt K, Dooms L, Proesmans W, de Zegher F, Desmet V, Eggermont E. Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: atypical Alagille syndrome? Eur J Pediatr. 1996;155(2):87–90.

    Article  CAS  PubMed  Google Scholar 

  61. Arvay JL, Zemel BS, Gallagher PR, Rovner AJ, Mulberg AE, Stallings VA, et al. Body composition of children aged 1 to 12 years with biliary atresia or Alagille syndrome. J Pediatr Gastroenterol Nutr. 2005;40(2):146–50.

    Article  PubMed  Google Scholar 

  62. Emerick KM, Krantz ID, Kamath BM, Darling C, Burrowes DM, Spinner NB, et al. Intracranial vascular abnormalities in patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2005;41(1):99–107.

    Article  PubMed  Google Scholar 

  63. Bucuvalas JC, Horn JA, Carlsson L, Balistreri WF, Chernausek SD. Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature. J Clin Endocrinol Metab. 1993;76(6):1477–82.

    CAS  PubMed  Google Scholar 

  64. Rennie CA, Chowdhury S, Khan J, Rajan F, Jordan K, Lamb RJ, et al. The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic. Eye. 2005;19(4):396–9.

    Article  CAS  PubMed  Google Scholar 

  65. Waring Iii GO, Rodrigues MM, Laibson PR. Anterior chamber cleavage syndrome. A stepladder classification. Surv Ophthalmol. 1975;20(1):3–27.

    Article  Google Scholar 

  66. Kim BJ, Fulton AB. The genetics and ocular findings of Alagille syndrome. Semin Ophthalmol. 2007;22(4):205–10.

    Article  PubMed  Google Scholar 

  67. Mayer U, Grosse KP. Clinical picture and inheritance of ocular symptoms in arteriohepatic dysplasia (author’s transl). Klin Monatsbl Augenheilkd. 1982;180(4):290–3.

    Article  CAS  PubMed  Google Scholar 

  68. Traboulsi EI, Lustbader JM, Lemp MA. Keratoconus in Alagille’s syndrome. Am J Ophthalmol. 1989;108(3):332–3.

    Article  CAS  PubMed  Google Scholar 

  69. Heathcote J, Deodhar KP, Scheuer PJ, Sherlock S. Intrahepatic cholestasis in childhood. N Engl J Med. 1976;295(15):801–5.

    Article  CAS  PubMed  Google Scholar 

  70. Fuchs A. White spots of the fundus combined with night blindness and xerosis (Uyemura’s syndrome). Am J Ophthalmol. 1959;48(1, Part 1):101–3.

    Article  CAS  PubMed  Google Scholar 

  71. Levy NS, Toskes PP. Fundus albipunctatus and vitamin A deficiency. Am J Ophthalmol. 1974;78(6):926–9.

    Article  CAS  PubMed  Google Scholar 

  72. Johnson BL. Ocular pathologic features of arteriohepatic dysplasia (Alagille’s syndrome). Am J Ophthalmol. 1990;110(5):504–12.

    Article  CAS  PubMed  Google Scholar 

  73. Tso MO. Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmology. 1981;88(10):1066–80.

    Article  CAS  PubMed  Google Scholar 

  74. Mullie MA, Sanders MD. Scleral canal size and optic nerve head drusen. Am J Ophthalmol. 1985;99(3):356–9.

    Article  CAS  PubMed  Google Scholar 

  75. Spinner NB, Leonard LD, Krantz ID. Alagille Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle, WA: University of Washington, Seattle; 1993.

    Google Scholar 

  76. Kamath BM, Yin W, Miller H, Anand R, Rand EB, Alonso E, et al. Outcomes of liver transplantation for patients with Alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transpl. 2012;18(8):940–8.

    Article  PubMed  Google Scholar 

  77. Longhi MS, Mieli-Vergani G, Vergani D. Autoimmune hepatitis. Curr Pediatr Rev. 2014;10(4):268–74.

    Article  CAS  PubMed  Google Scholar 

  78. Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol. 2004;41(4):677–83.

    Article  PubMed  Google Scholar 

  79. Liberal R, Grant CR, Longhi MS, Mieli-Vergani G, Vergani D. Diagnostic criteria of autoimmune hepatitis. Autoimmun Rev. 2014;13(4–5):435–40.

    Article  CAS  PubMed  Google Scholar 

  80. Mackay IR. Historical reflections on autoimmune hepatitis. World J Gastroenterol. 2008;14(21):3292–300.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Mackay IR. Toward diagnostic criteria for autoimmune hepatitis. Hepatology. 1993;18(4):1006–8.

    Article  CAS  PubMed  Google Scholar 

  82. Mieli-Vergani G, Vergani D. Paediatric autoimmune liver disease. Arch Dis Child. 2013;98(12):1012–17.

    Article  PubMed  Google Scholar 

  83. Ngu JH, Bechly K, Chapman BA, Burt MJ, Barclay ML, Gearry RB, et al. Population-based epidemiology study of autoimmune hepatitis: a disease of older women? J Gastroenterol Hepatol. 2010;25(10):1681–6.

    Article  PubMed  Google Scholar 

  84. Bloom JN, Rabinowicz IM, Shulman ST. Uveitis complicating autoimmune chronic active hepatitis. Am J Dis Child. 1983;137(12):1175–6.

    CAS  PubMed  Google Scholar 

  85. Lim LL, Scarborough JD, Thorne JE, Graham E, Kempen JH, Mackensen F, et al. Uveitis in patients with autoimmune hepatitis. Am J Ophthalmol. 2009;147(2):332–8. e1.

    Article  PubMed  Google Scholar 

  86. Sires BS, Goodrich SD, Holds JB. Spontaneous orbital hemorrhage in a child with autoimmune hepatitis. Am J Ophthalmol. 1993;116(3):384–5.

    Article  CAS  PubMed  Google Scholar 

  87. Sarkhy A, Persad R, Tarnopolsky M. Muscle weakness in a girl with autoimmune hepatitis and Graves’ disease. Eur J Pediatr. 2009;168(2):241–3.

    Article  PubMed  Google Scholar 

  88. Saadah OI, Smith AL, Hardikar W. Long-term outcome of autoimmune hepatitis in children. J Gastroenterol Hepatol. 2001;16(11):1297–302.

    Article  CAS  PubMed  Google Scholar 

  89. Nel E, Sokol RJ, Comparcola D, Nobili V, Hardikar W, Gana JC, et al. Viral hepatitis in children. J Pediatr Gastroenterol Nutr. 2012;55(5):500–5.

    Article  PubMed  Google Scholar 

  90. Jacobsen KH. The global prevalence of hepatitis A virus infection and susceptibility: a systematic review. Geneva, Switzerland: World Health Organization; 2009.

    Google Scholar 

  91. Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev. 2001;14(1):38–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Feinstone SM, Kapikian AZ, Purceli RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science. 1973;182(4116):1026–8.

    Article  CAS  PubMed  Google Scholar 

  93. Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010;28(41):6653–7.

    Article  PubMed  Google Scholar 

  94. Varona L, Sagasta A, Martin-Gonzalvez JA, Ruiz J, Zarranz JJ. Cranial neuropathies and liver failure due to hepatitis A. Neurology. 1996;46(6):1774–5.

    Article  CAS  PubMed  Google Scholar 

  95. Jouhadi Z, Ouazzani I, Abid A, El Moutawakil B, Rafai MA, Slassi I. Devic’s optic neuromyelitis and viral hepatitis type A. A paediatric case report. Rev Neurol. 2004;160(12):1198–202.

    Article  CAS  PubMed  Google Scholar 

  96. Dienstag JL. Hepatitis B, virus infection. N Engl J Med. 2008;359(14):1486–500.

    Article  CAS  PubMed  Google Scholar 

  97. Senior JR, London WT, Sutnick AI. The Australia antigen and role of the late Philadelphia general hospital in reducing post-transfusion hepatitis and sequelae. Hepatology. 2011;54(3):753–6.

    Article  PubMed  Google Scholar 

  98. Lee WM. Hepatitis B, virus infection. N Engl J Med. 1997;337(24):1733–45.

    Article  CAS  PubMed  Google Scholar 

  99. Blumberg BS. Australia antigen and the biology of hepatitis B. Science. 1977;197(4298):17–25.

    Article  CAS  PubMed  Google Scholar 

  100. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55.

    Article  PubMed  Google Scholar 

  101. Matthews G, Robotin M, Allard N. B Positive—All you wanted to know about hepatitis B: Australasian Society for HIV Medicine. 2014. http://hepbpositive.com.au/wp-content/uploads/2014/10/BPOS_Monograph_2014.pdf. Accessed 15 Oct 2015.

  102. Kappus MR, Sterling RK. Extrahepatic manifestations of acute hepatitis B virus infection. Gastroenterol Hepatol. 2013;9(2):123–6.

    Google Scholar 

  103. Kwon YS, Choe YH, Chin HS. Development of glaucoma in the course of interferon alpha therapy for chronic hepatitis B. Yonsei Med J. 2001;42(1):134–6.

    Article  CAS  PubMed  Google Scholar 

  104. WHO. Hepatitis C 2015. Accessed from: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index4.html.

  105. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244(4902):359–62.

    Article  CAS  PubMed  Google Scholar 

  106. Galossi A, Guarisco R, Bellis L, Puoti C. Extrahepatic manifestations of chronic HCV infection. J Gastrointestin Liver Dis. 2007;16(1):65–73.

    PubMed  Google Scholar 

  107. Ertekin V, Tan H. Opsoclonus-myoclonus syndrome attributable to hepatitis C infection. Pediatr Neurol. 2010;42(6):441–2.

    Article  PubMed  Google Scholar 

  108. Hero B, Schleiermacher G. Update on pediatric opsoclonus myoclonus syndrome. Neuropediatrics. 2013;44(6):324–9.

    Article  PubMed  Google Scholar 

  109. Wong A. An update on opsoclonus. Curr Opin Neurol. 2007;20(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  110. Indolfi G, Bartolini E, Olivito B, Azzari C, Resti M. Autoimmunity and extrahepatic manifestations in treatment-naive children with chronic hepatitis C virus infection. Clin Dev Immunol. 2012;2012:785627.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA. 2014;312(6):631–40.

    Article  CAS  PubMed  Google Scholar 

  112. Dalton HR, Hunter JG, Bendall RP. Hepatitis E. Curr Opin Infect Dis. 2013;26(5):471–8.

    PubMed  Google Scholar 

  113. Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J, et al. Hepatitis E. Lancet. 2012;379(9835):2477–88.

    Article  PubMed  Google Scholar 

  114. Reyes GR, Purdy MA, Kim JP, Luk KC, Young LM, Fry KE, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990;247(4948):1335–9.

    Article  CAS  PubMed  Google Scholar 

  115. Teshale EH, Hu DJ, Holmberg SD. The two faces of hepatitis E virus. Clin Infect Dis. 2010;51(3):328–34.

    Article  PubMed  Google Scholar 

  116. Yadav KK, Rohatgi A, Sharma SK, Kulshrestha M, Sachdeva S, Pardasani V. Oculomotor palsy associated with hepatitis E infection. J Assoc Physicians India. 2002;50(5):737.

    CAS  PubMed  Google Scholar 

  117. Gunay-Aygun M, Gahl WA, Heller T. Congenital hepatic fibrosis overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle, WA: University of Washington, Seattle; 1993.

    Google Scholar 

  118. Rock N, McLin V. Liver involvement in children with ciliopathies. Clin Res Hepatol Gastroenterol. 2014;38(4):407–14.

    Article  CAS  PubMed  Google Scholar 

  119. Gentile M, Di Carlo A, Susca F, Gambotto A, Caruso ML, Panella C, et al. COACH syndrome: report of two brothers with congenital hepatic fibrosis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation. Am J Med Genet. 1996;64(3):514–20.

    Article  CAS  PubMed  Google Scholar 

  120. Verloes A, Lambotte C. Further delineation of a syndrome of cerebellar vermis hypo/aplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis. Am J Med Genet. 1989;32(2):227–32.

    Article  CAS  PubMed  Google Scholar 

  121. Doherty D, Parisi MA, Finn LS, Gunay-Aygun M, Al-Mateen M, Bates D, et al. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). J Med Genet. 2010;47(1):8–21.

    Article  CAS  PubMed  Google Scholar 

  122. Brancati F, Iannicelli M, Travaglini L, Mazzotta A, Bertini E, Boltshauser E, et al. MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement. Hum Mutat. 2009;30(2):E432–42.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Szymanska K, Hartill VL, Johnson CA. Unraveling the genetics of Joubert and Meckel-Gruber syndromes. J Pediatr Genet. 2014;3(2):65–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Kerr DN, Harrison CV, Sherlock S, Walker RM. Congenital hepatic fibrosis. Q J Med. 1961;30:91–117.

    CAS  PubMed  Google Scholar 

  125. Hunter AG, Rothman SJ, Hwang WS, Deckelbaum RJ. Hepatic fibrosis, polycystic kidney, colobomata and encephalopathy in siblings. Clin Genet. 1974;6(2):82–9.

    Article  CAS  PubMed  Google Scholar 

  126. Acharyya BC, Goenka MK, Chatterjee S, Goenka U. Dealing with congenital hepatic fibrosis? Remember COACH syndrome. Clin J Gastroenterol. 2014;7(1):48–51.

    Article  CAS  PubMed  Google Scholar 

  127. Weiland MD, Nowicki MJ, Jones JK, Giles HW. COACH syndrome: an unusual cause of neonatal cholestasis. J Pediatr. 2011;158(5):858.e1.

    Article  Google Scholar 

  128. Foell D, August C, Frosch M, Harms E, Zimmer KP. Early detection of severe cholestatic hepatopathy in COACH syndrome. Am J Med Genet. 2002;111(4):429–34.

    Article  PubMed  Google Scholar 

  129. Sanjeev RK, Kapoor S, Goyal M, Kapur R, Gleeson JG. Molar tooth sign with deranged liver function tests: an Indian case with COACH syndrome. Case Rep Pediatr. 2015;2015:385910.

    PubMed  PubMed Central  Google Scholar 

  130. Kumar S, Rankin R. Renal insufficiency is a component of COACH syndrome. Am J Med Genet. 1996;61(2):122–6.

    Article  CAS  PubMed  Google Scholar 

  131. Minami K, Izumi G, Yanagawa T, Shimoyamada Y, Yoshikawa N. Septo-optic dysplasia with congenital hepatic fibrosis. Pediatr Neurol. 2003;29(2):157–9.

    Article  PubMed  Google Scholar 

  132. Fahnehjelm KT, Fischler B, Jacobson L, Nemeth A. Optic nerve hypoplasia in cholestatic infants: a multiple case study. Acta Ophthalmol Scand. 2003;81(2):130–7.

    Article  PubMed  Google Scholar 

  133. Spray CH, McKiernan P, Waldron KE, Shaw N, Kirk J, Kelly DA. Investigation and outcome of neonatal hepatitis in infants with hypopituitarism. Acta Paediatr. 2000;89(8):951–4.

    Article  CAS  PubMed  Google Scholar 

  134. Singh V, Bhattacharjee S, Singh K, Narula MK. Leber’s amaurosis with nephronophthisis and congenital hepatic fibrosis. Indian Pediatr. 2004;41(10):1053–6.

    PubMed  Google Scholar 

  135. Barzilai M, Ish-Shalom N, Lerner A, Iancu TC. Imaging findings in COACH syndrome. AJR Am J Roentgenol. 1998;170(4):1081–2.

    Article  CAS  PubMed  Google Scholar 

  136. Rawat D, Kelly DA, Milford DV, Sharif K, Lloyd C, McKiernan PJ. Phenotypic variation and long-term outcome in children with congenital hepatic fibrosis. J Pediatr Gastroenterol Nutr. 2013;57(2):161–6.

    Article  PubMed  Google Scholar 

  137. Whitington PF. Gestational alloimmune liver disease and neonatal hemochromatosis. Semin Liver Dis. 2012;32(4):325–32.

    CAS  PubMed  Google Scholar 

  138. Feldman AG, Whitington PF. Neonatal hemochromatosis. J Clin Exp Hepatol. 2013;3(4):313–20.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Durand P, Debray D, Mandel R, Baujard C, Branchereau S, Gauthier F, et al. Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center. J Pediatr. 2001;139(6):871–6.

    Article  CAS  PubMed  Google Scholar 

  140. Maldonado RS, Freedman SF, Cotten CM, Ferranti JM, Toth CA. Reversible retinal edema in an infant with neonatal hemochromatosis and liver failure. J AAPOS. 2011;15(1):91–3.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Whitington PF. Neonatal hemochromatosis: a congenital alloimmune hepatitis. Semin Liver Dis. 2007;27(3):243–50.

    Article  CAS  PubMed  Google Scholar 

  142. Heissat S, Collardeau-Frachon S, Baruteau J, Dubruc E, Bouvier R, Fabre M, et al. Neonatal hemochromatosis: diagnostic work-up based on a series of 56 cases of fetal death and neonatal liver failure. J Pediatr. 2015;166(1):66–73.

    Article  PubMed  Google Scholar 

  143. Whitington PF, Kelly S. Outcome of pregnancies at risk for neonatal hemochromatosis is improved by treatment with high-dose intravenous immunoglobulin. Pediatrics. 2008;121(6):e1615–21.

    Article  PubMed  Google Scholar 

  144. Mosier HD. Hypoplasia of the pituitary and adrenal cortex; report of occurrence in twin siblings and autopsy findings. J Pediatr. 1956;48(5):633–9.

    Article  CAS  PubMed  Google Scholar 

  145. Karnsakul W, Sawathiparnich P, Nimkarn S, Likitmaskul S, Santiprabhob J, Aanpreung P. Anterior pituitary hormone effects on hepatic functions in infants with congenital hypopituitarism. Ann Hepatol. 2007;6(2):97–103.

    CAS  PubMed  Google Scholar 

  146. Ellaway CJ, Silinik M, Cowell CT, Gaskin KJ, Kamath KR, Dorney S, et al. Cholestatic jaundice and congenital hypopituitarism. J Paediatr Child Health. 1995;31(1):51–3.

    Article  CAS  PubMed  Google Scholar 

  147. Cools F, Jaeken J. Hardikar syndrome: a new syndrome with cleft lip/palate, pigmentary retinopathy and cholestasis. Am J Med Genet. 1997;71(4):472–4.

    Article  CAS  PubMed  Google Scholar 

  148. Hardikar W, Smith AL, Keith CG, Chow CW. Multisystem obstruction with cholestasis, pigmentary retinopathy, and cleft palate: a new syndrome? Am J Med Genet. 1992;44(1):13–7.

    Article  CAS  PubMed  Google Scholar 

  149. Maluf DG, Fisher RA, Fulcher AS, Posner MP. Hardikar syndrome: a case requiring liver transplantation. Transplantation. 2002;74(7):1058–61.

    Article  PubMed  Google Scholar 

  150. Poley JR, Proud VK. Hardikar syndrome: new features. Am J Med Genet A. 2008;146(19):2473–9.

    Article  Google Scholar 

  151. Nydegger A, Van Dyck M, Fisher RA, Jaeken J, Hardikar W. Hardikar syndrome: long term outcome of a rare genetic disorder. Am J Med Genet A. 2008;146A(19):2468–72.

    Article  PubMed  Google Scholar 

  152. Leoz ML, Carballal S, Moreira L, Ocana T, Balaguer F. The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. Appl Clin Genet. 2015;8:95–107.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991;253(5020):665–9.

    Article  CAS  PubMed  Google Scholar 

  154. Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, et al. The molecular basis of Turcot’s syndrome. N Engl J Med. 1995;332(13):839–47.

    Article  CAS  PubMed  Google Scholar 

  155. Gardner EJ. A genetic and clinical study of intestinal polyposis, a predisposing factor for carcinoma of the colon and rectum. Am J Hum Genet. 1951;3(2):167–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Gardner EJ, Plenk HP. Hereditary pattern for multiple osteomas in a family group. Am J Hum Genet. 1952;4(1):31–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner’s syndrome. Am J Ophthalmol. 1980;90(5):661–7.

    Article  CAS  PubMed  Google Scholar 

  158. McKittrick LS, Talbott JH, Mallory TB. Case 21061. N Engl J Med. 1935;212(6):263–7.

    Article  Google Scholar 

  159. Cohen S, Gorodnichenco A, Weiss B, Lerner A, Ben-Tov A, Yaron A, et al. Polyposis syndromes in children and adolescents: a case series data analysis. Eur J Gastroenterol Hepatol. 2014;26(9):972–7.

    Article  PubMed  Google Scholar 

  160. Naylor EW, Gardner EJ. Penetrance and expressivity of the gene responsible for the Gardner syndrome. Clin Genet. 1977;11(6):381–93.

    CAS  PubMed  Google Scholar 

  161. Danes BS, Gardner EJ. The Gardner syndrome: a cell culture study on kindred 109. J Med Genet. 1978;15(5):346–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Shields JA, Shields CL, Shah PG, Pastore DJ, Imperiale Jr SM. Lack of association among typical congenital hypertrophy of the retinal pigment epithelium, adenomatous polyposis, and Gardner syndrome. Ophthalmology. 1992;99(11):1709–13.

    Article  CAS  PubMed  Google Scholar 

  163. Ellis FD. Selected pigmented fundus lesions of children. J AAPOS. 2005;9(4):306–14.

    Article  PubMed  Google Scholar 

  164. Shields CL, Mashayekhi A, Ho T, Cater J, Shields JA. Solitary congenital hypertrophy of the retinal pigment epithelium: clinical features and frequency of enlargement in 330 patients. Ophthalmology. 2003;110(10):1968–76.

    Article  PubMed  Google Scholar 

  165. Tourino R, Rodriguez-Ares MT, Lopez-Valladares MJ, Gomez-Ulla F, Gomez-Torreiro M, Capeans C. Fluorescein angiographic features of the congenital hypertrophy of the retinal pigment epithelium in the familial adenomatous polyposis. Int Ophthalmol. 2005;26(1–2):59–65.

    PubMed  Google Scholar 

  166. Shields CL, Materin MA, Walker C, Marr BP, Shields JA. Photoreceptor loss overlying congenital hypertrophy of the retinal pigment epithelium by optical coherence tomography. Ophthalmology. 2006;113(4):661–5.

    Article  PubMed  Google Scholar 

  167. Tzu JH, Cavuoto KM, Villegas VM, Dubovy SR, Capo H. Optical coherence tomography findings of pigmented fundus lesions in familial adenomatous polyposis. Ophthalmic Surg Lasers Imaging Retina. 2014;45(1):69–70.

    Article  PubMed  Google Scholar 

  168. Traboulsi EI, Krush AJ, Gardner EJ, Booker SV, Offerhaus GJ, Yardley JH, et al. Prevalence and importance of pigmented ocular fundus lesions in Gardner’s syndrome. N Engl J Med. 1987;316(11):661–7.

    Article  CAS  PubMed  Google Scholar 

  169. Diaz-Llopis M, Menezo JL. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Arch Ophthalmol. 1988;106(3):412–13.

    Article  CAS  PubMed  Google Scholar 

  170. Lyons LA, Lewis RA, Strong LC, Zuckerbrod S, Ferrell RE. A genetic study of Gardner syndrome and congenital hypertrophy of the retinal pigment epithelium. Am J Hum Genet. 1988;42(2):290–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Coleman P, Barnard NA. Congenital hypertrophy of the retinal pigment epithelium: prevalence and ocular features in the optometric population. Ophthalmic Physiol Opt. 2007;27(6):547–55.

    Article  PubMed  Google Scholar 

  172. Shields JA, Shields CL, Singh AD. Acquired tumors arising from congenital hypertrophy of the retinal pigment epithelium. Arch Ophthalmol. 2000;118(5):637–41.

    Article  CAS  PubMed  Google Scholar 

  173. Shields JA, Shields CL, Eagle Jr RC, Singh AD. Adenocarcinoma arising from congenital hypertrophy of retinal pigment epithelium. Arch Ophthalmol. 2001;119(4):597–602.

    Article  CAS  PubMed  Google Scholar 

  174. Lewis RA, Crowder WE, Eierman LA, Nussbaum RL, Ferrell RE. The Gardner syndrome. Significance of ocular features. Ophthalmology. 1984;91(8):916–25.

    Article  CAS  PubMed  Google Scholar 

  175. Baker RH, Heinemann MH, Miller HH, DeCosse JJ. Hyperpigmented lesions of the retinal pigment epithelium in familial adenomatous polyposis. Am J Med Genet. 1988;31(2):427–35.

    Article  CAS  PubMed  Google Scholar 

  176. Stein EA, Brady KD. Ophthalmologic and electro-oculographic findings in Gardner’s syndrome. Am J Ophthalmol. 1988;106(3):326–31.

    Article  CAS  PubMed  Google Scholar 

  177. Chapman PD, Church W, Burn J, Gunn A. Congenital hypertrophy of retinal pigment epithelium: a sign of familial adenomatous polyposis. BMJ. 1989;298(6670):353–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Traboulsi EI, Maumenee IH, Krush AJ, Alcorn D, Giardiello FM, Burt RW, et al. Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polyposis in Gardner’s syndrome. Arch Ophthalmol. 1990;108(4):525–6.

    Article  CAS  PubMed  Google Scholar 

  179. Burn J, Chapman P, Delhanty J, Wood C, Lalloo F, Cachon-Gonzalez MB, et al. The UK Northern region genetic register for familial adenomatous polyposis coli: use of age of onset, congenital hypertrophy of the retinal pigment epithelium, and DNA markers in risk calculations. J Med Genet. 1991;28(5):289–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Giardiello FM, Offerhaus GJ, Traboulsi EI, Graybeal JC, Maumenee IH, Krush AJ, et al. Value of combined phenotypic markers in identifying inheritance of familial adenomatous polyposis. Gut. 1991;32(10):1170–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Houlston RS, Fallon T, Harocopos C, Williams CB, Davey C, Slack J. Congenital hypertrophy of retinal pigment epithelium in patients with colonic polyps associated with cancer family syndrome. Clin Genet. 1992;42(1):16–8.

    Article  CAS  PubMed  Google Scholar 

  182. Moore AT, Maher ER, Koch DJ, Charles SJ. Incidence and significance of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in familial adenomatous polyposis coli (FAPC). Ophthalmic Paediatr Genet. 1992;13(2):67–71.

    Article  CAS  PubMed  Google Scholar 

  183. Romania A, Zakov ZN, Church JM, Jagelman DG. Retinal pigment epithelium lesions as a biomarker of disease in patients with familial adenomatous polyposis. A follow-up report. Ophthalmology. 1992;99(6):911–13.

    Article  CAS  PubMed  Google Scholar 

  184. Aiello LP, Traboulsi EI. Pigmented fundus lesions in a preterm infant with familial adenomatous polyposis. Arch Ophthalmol. 1993;111(3):302–3.

    Article  CAS  PubMed  Google Scholar 

  185. Parker JA, Berk T, Bapat BV. Familial variation in retinal pigmentation in adenomatous polyposis. Can J Ophthalmol. 1995;30(3):138–41.

    CAS  PubMed  Google Scholar 

  186. Rossato M, Rigotti M, Grazia M, Turco AE, Bonomi L. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and familial adenomatous polyposis (FAP). Acta Ophthalmol Scand. 1996;74(4):338–42.

    Article  CAS  PubMed  Google Scholar 

  187. Traboulsi EI, Apostolides J, Giardiello FM, Krush AJ, Booker SV, Hamilton SR, et al. Pigmented ocular fundus lesions and APC mutations in familial adenomatous polyposis. Ophthalmic Genet. 1996;17(4):167–74.

    Article  CAS  PubMed  Google Scholar 

  188. Valanzano R, Cama A, Volpe R, Curia MC, Mencucci R, Palmirotta R, et al. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. Novel criteria of assessment and correlations with constitutional adenomatous polyposis coli gene mutations. Cancer. 1996;78(11):2400–10.

    Article  CAS  PubMed  Google Scholar 

  189. Gelisken O, Yucel A, Guler K, Zorluoglu A. Ocular findings in familial adenomatous polyposis. Int Ophthalmol. 1997;21(4):205–8.

    Article  PubMed  Google Scholar 

  190. Giardiello FM, Petersen GM, Piantadosi S, Gruber SB, Traboulsi EI, Offerhaus GJ, et al. APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis. Gut. 1997;40(4):521–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Ruhswurm I, Zehetmayer M, Dejaco C, Wolf B, Karner-Hanusch J. Ophthalmic and genetic screening in pedigrees with familial adenomatous polyposis. Am J Ophthalmol. 1998;125(5):680–6.

    Article  CAS  PubMed  Google Scholar 

  192. Ganesh A, Kaliki S, Levin AV, Shields CL. Epiretinal membrane and retinal pigment epithelial lesions in a young child and detection of de novo APC mutation. Arch Ophthalmol. 2012;130(8):1071–3.

    Article  PubMed  Google Scholar 

  193. Kochhar R, Nehru V, Gupta NM, Mehra YN, Malik AD, Mehta SK. Gardner’s syndrome presenting with proptosis. J Assoc Physicians India. 1987;35(12):849–50.

    CAS  PubMed  Google Scholar 

  194. Armstrong SJ, Duncan AW, Mott MG. Rhabdomyosarcoma associated with familial adenomatous polyposis. Pediatr Radiol. 1991;21(6):445–6.

    Article  CAS  PubMed  Google Scholar 

  195. Li QX, Liu CX, Chun CP, Qi Y, Chang B, Li XX, et al. Chromosomal imbalances revealed in primary rhabdomyo-sarcomas by comparative genomic hybridization. Chin Med J. 2009;122(11):1277–82.

    CAS  PubMed  Google Scholar 

  196. Kiratli H, Bilgic S, Ozerdem U. Retinoblastoma with acute lymphoblastic leukemia, polyposis coli, and multiple hamartomas. J AAPOS. 1998;2(6):385–6.

    Article  CAS  PubMed  Google Scholar 

  197. Sheta SS, El-Toukhy EA, Khattab HM. Optic nerve glioma and colonic polyposis: report of a new association. Acta Paediatr. 2004;93(9):1259–60.

    Article  CAS  PubMed  Google Scholar 

  198. Lima BR, Schoenfield L, Rychwalski PJ. Germinoma presenting as a fourth cranial nerve palsy in a patient with adenomatous polyposis coli (APC) gene mutation. J AAPOS. 2011;15(1):71–3.

    Article  PubMed  Google Scholar 

  199. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62. quiz 63.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Jelsig AM, Qvist N, Brusgaard K, Nielsen CB, Hansen TP, Ousager LB. Hamartomatous polyposis syndromes: a review. Orphanet J Rare Dis. 2014;9:101.

    Article  PubMed  PubMed Central  Google Scholar 

  201. van Lier MG, Wagner A, Mathus-Vliegen EM, Kuipers EJ, Steyerberg EW, van Leerdam ME. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am J Gastroenterol. 2010;105(6):1258–64. author reply 65.

    Article  PubMed  Google Scholar 

  202. Jeghers H. Pigmentation of the Skin. N Engl J Med. 1944;231(4):122–36.

    Article  Google Scholar 

  203. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl J Med. 1949;241(25):993. illust; passim.

    Article  CAS  PubMed  Google Scholar 

  204. Jeghers H, McKusick VA, Katz KH. Generalized intestinal polyposis and melanin spots of the oral mucosa, lips and digits; a syndrome of diagnostic significance. N Engl J Med. 1949;241(26):1031–6.

    Article  CAS  PubMed  Google Scholar 

  205. Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38–43.

    Article  CAS  PubMed  Google Scholar 

  206. Jass JR. Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract. 2008;204(7):431–47.

    Article  PubMed  Google Scholar 

  207. Raizis AM, Van Mater D, Aaltonen LA, Lohmann D, Cheale MS, Bickley VM, et al. Trilateral retinoblastoma in a patient with Peutz-Jeghers syndrome. Am J Med Genet A. 2013;161A(5):1096–100.

    Article  PubMed  CAS  Google Scholar 

  208. Mester J, Eng C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol. 2015;111(1):125–30.

    Article  PubMed  Google Scholar 

  209. Blumenthal GM, Dennis PA. PTEN hamartoma tumor syndromes. Eur J Hum Genet. 2008;16(11):1289–300.

    Article  CAS  PubMed  Google Scholar 

  210. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet. 1999;8(8):1461–72.

    Article  CAS  PubMed  Google Scholar 

  211. Cohen Jr MM, Turner JT, Biesecker LG. Proteus syndrome: misdiagnosis with PTEN mutations. Am J Med Genet A. 2003;122(4):323–4.

    Article  Google Scholar 

  212. Lloyd 2nd KM, Dennis M. Cowden’s disease. A possible new symptom complex with multiple system involvement. Ann Intern Med. 1963;58:136–42.

    Article  PubMed  Google Scholar 

  213. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet. 1997;16(1):64–7.

    Article  CAS  PubMed  Google Scholar 

  214. Nelen MR, Kremer H, Konings IB, Schoute F, van Essen AJ, Koch R, et al. Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999;7(3):267–73.

    Article  CAS  PubMed  Google Scholar 

  215. Nuss DD, Aeling JL, Clemons DE, Weber WN. Multiple hamartoma syndrome (Cowden’s disease). Arch Dermatol. 1978;114(5):743–6.

    Article  CAS  PubMed  Google Scholar 

  216. Wells GB, Lasner TM, Yousem DM, Zager EL. Lhermitte-Duclos disease and Cowden’s syndrome in an adolescent patient. Case report. J Neurosurg. 1994;81(1):133–6.

    Article  CAS  PubMed  Google Scholar 

  217. Arch EM, Goodman BK, Van Wesep RA, Liaw D, Clarke K, Parsons R, et al. Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease. Am J Med Genet. 1997;71(4):489–93.

    Article  CAS  PubMed  Google Scholar 

  218. Schaffer JV, Kamino H, Witkiewicz A, McNiff JM, Orlow SJ. Mucocutaneous neuromas: an underrecognized manifestation of PTEN hamartoma-tumor syndrome. Arch Dermatol. 2006;142(5):625–32.

    Article  PubMed  Google Scholar 

  219. Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.

    Article  CAS  PubMed  Google Scholar 

  220. Ledder O, Catto-Smith AG, Oliver MR, Alex G, Cameron DJ, Hardikar W. Clinical patterns and outcome of early-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2014;59(5):562–4.

    Article  PubMed  Google Scholar 

  221. Fengming Y, Jianbing W. Biomarkers of inflammatory bowel disease. Dis Markers. 2014;2014:710915.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  222. Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci. 1999;44(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  223. Mady R, Grover W, Butrus S. Ocular complications of inflammatory bowel disease. ScientificWorldJournal. 2015;2015:438402.

    Article  PubMed  PubMed Central  Google Scholar 

  224. Crohn BB, Ginzburg L, Oppenheimer GD. Regional ileitis: a pathologic and clinical entity. J Am Med Assoc. 1932;99(16):1323–9.

    Article  Google Scholar 

  225. Wilks S. Lectures on pathological Diseases. 1st ed. Philadelphia, PA: Lindsay and Blankiston; 1859.

    Google Scholar 

  226. Maxwell EM, Kiep WH. Notes on six cases of iritis and cyclitis occurring in dysenteric patients. Br J Ophthalmol. 1918;2(2):71–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Crohn BB. Ocular lesions complicating ulcerative colitis. Am J Med Sci. 1925;169(2):260–7.

    Google Scholar 

  228. Billson FA, De Dombal FT, Watkinson G, Goligher JC. Ocular complications of ulcerative colitis. Gut. 1967;8(2):102–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Korelitz BI, Coles RS. Uveitis (iritis) associated with ulcerative and granulomatous colitis. Gastroenterology. 1967;52(1):78–82.

    CAS  PubMed  Google Scholar 

  230. Hopkins DJ, Horan E, Burton IL, Clamp SE, de Dombal FT, Goligher JC. Ocular disorders in a series of 332 patients with Crohn’s disease. Br J Ophthalmol. 1974;58(8):732–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Schildkraut V, Alex G, Cameron DJ, Hardikar W, Lipschitz B, Oliver MR, et al. Sixty-year study of incidence of childhood ulcerative colitis finds eleven-fold increase beginning in 1990s. Inflamm Bowel Dis. 2013;19(1):1–6.

    Article  PubMed  Google Scholar 

  232. de Groof J, Rossen N, van Rhijn B, Karregat E, Boonstra K, Hageman I, et al. P664 Epidemiology and characteristics of inflammatory bowel disease in a large population-based cohort in the Netherlands. J Crohns Colitis. 2015;9 Suppl 1:S404–5.

    Google Scholar 

  233. Fernandez A, Hernandez V, Martinez-Ares D, Sanroman L, de Castro ML, Pineda JR, et al. Incidence and phenotype at diagnosis of inflammatory bowel disease. Results in Spain of the EpiCom study. Gastroenterol Hepatol. 2015.

    Google Scholar 

  234. Hilmi I, Jaya F, Chua A, Heng WC, Singh H, Goh KL. A first study on the incidence and prevalence of IBD in Malaysia-results from the Kinta valley IBD epidemiology study. J Crohns Colitis. 2015;9(5):404–9.

    Article  PubMed  Google Scholar 

  235. Yoon CM, Kim SB, Park IJ, Bom HS, Rhew JS, Choi SK, et al. Clinical features of Crohn’s disease in Korea. Gastroenterol Jpn. 1988;23(5):576–81.

    CAS  PubMed  Google Scholar 

  236. Mendoza JL, Lana R, Taxonera C, Alba C, Izquierdo S, Diaz-Rubio M. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis. Med Clin. 2005;125(8):297–300.

    Article  Google Scholar 

  237. Yilmaz S, Aydemir E, Maden A, Unsal B. The prevalence of ocular involvement in patients with inflammatory bowel disease. Int J Color Dis. 2007;22(9):1027–30.

    Article  Google Scholar 

  238. Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol. 2011;7(4):235–41.

    Google Scholar 

  239. Yuksel I, Basar O, Ataseven H, Ertugrul I, Arhan M, Ibis M, et al. Mucocutaneous manifestations in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(4):546–50.

    Article  PubMed  Google Scholar 

  240. Lebwohl M, Lebwohl O. Cutaneous manifestations of inflammatory bowel disease. Inflamm Bowel Dis. 1998;4(2):142–8.

    CAS  PubMed  Google Scholar 

  241. Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn’s disease. Ophthalmology. 1984;91(2):163–73.

    Article  CAS  PubMed  Google Scholar 

  242. Zippi M, Corrado C, Pica R, Avallone EV, Cassieri C, De Nitto D, et al. Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients. World J Gastroenterol. 2014;20(46):17463–7.

    Article  PubMed  PubMed Central  Google Scholar 

  243. Hofley P, Roarty J, McGinnity G, Griffiths AM, Marcon M, Kraft S, et al. Asymptomatic uveitis in children with chronic inflammatory bowel diseases. J Pediatr Gastroenterol Nutr. 1993;17(4):397–400.

    Article  CAS  PubMed  Google Scholar 

  244. Rychwalski PJ, Cruz OA, Alanis-Lambreton G, Foy TM, Kane RE. Asymptomatic uveitis in young people with inflammatory bowel disease. J AAPOS. 1997;1(2):111–14.

    Article  CAS  PubMed  Google Scholar 

  245. Daum F, Gould HB, Gold D, Dinari G, Friedman AH, Zucker P, et al. Asymptomatic transient uveitis in children with inflammatory bowel disease. Am J Dis Child. 1979;133(2):170–1.

    CAS  PubMed  Google Scholar 

  246. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine. 1976;55(5):401–12.

    Article  CAS  PubMed  Google Scholar 

  247. Pettei MJ, Davidson M. Extra gastrointestinal manifestations of inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1985;4(5):689–91.

    CAS  PubMed  Google Scholar 

  248. Blase WP, Knox DL, Green WR. Granulomatous conjunctivitis in a patient with Crohn’s disease. Br J Ophthalmol. 1984;68(12):901–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Ellis PP, Gentry JH. Ocular complications of ulcerative colitis. Am J Ophthalmol. 1964;58:779–85.

    Article  CAS  PubMed  Google Scholar 

  250. Salmon JF, Wright JP, Murray AD. Ocular inflammation in Crohn’s disease. Ophthalmology. 1991;98(4):480–4.

    Article  CAS  PubMed  Google Scholar 

  251. Cloche V, Buisson A, Trechot F, Batta B, Locatelli A, Favel C, et al. Ocular symptoms are not predictive of ophthalmologic inflammation in inflammatory bowel disease. Dig Liver Dis. 2013;45(3):195–9.

    Article  PubMed  Google Scholar 

  252. Fasci-Spurio F, Thompson A, Madill S, Koay P, Mansfield D, Satsangi J. Sight-threatening keratopathy complicating anti-TNF therapy in Crohn’s disease: a case report. Inflamm Bowel Dis. 2014;20(1):E2–3.

    Article  PubMed  Google Scholar 

  253. Lind E, Fausa O, Elgjo K, Gjone E. Crohn’s disease. Clinical manifestations. Scand J Gastroenterol. 1985;20(6):665–70.

    Article  CAS  PubMed  Google Scholar 

  254. Macoul KL. Ocular changes in granulomatous ileocolitis. Arch Ophthalmol. 1970;84(1):95–7.

    Article  CAS  PubMed  Google Scholar 

  255. Sahel J, De Korvin H, Annonier P, Jouin H, Brini A. Corneoscleral involvement in Crohn’s disease. Discussion of a case. J Fr Ophtalmol. 1986;9(2):111–14.

    CAS  PubMed  Google Scholar 

  256. Tripathi RC, Kipp MA, Tripathi BJ, Kirschner BS, Borisuth NS, Shevell SK, et al. Ocular toxicity of prednisone in pediatric patients with inflammatory bowel disease. Lens Eye Toxic Res. 1992;9(3–4):469–82.

    CAS  PubMed  Google Scholar 

  257. Tripathi RC, Kirschner BS, Kipp M, Tripathi BJ, Slotwiner D, Borisuth NS, et al. Corticosteroid treatment for inflammatory bowel disease in pediatric patients increases intraocular pressure. Gastroenterology. 1992;102(6):1957–61.

    Article  CAS  PubMed  Google Scholar 

  258. Hutnik CM, Nicolle DA, Canny CL. Papillitis: a rare initial presentation of Crohn’s disease. Can J Ophthalmol. 1996;31(7):373–6.

    CAS  PubMed  Google Scholar 

  259. Liu GT, Kay MD, Bienfang DC, Schatz NJ. Pseudotumor cerebri associated with corticosteroid withdrawal in inflammatory bowel disease. Am J Ophthalmol. 1994;117(3):352–7.

    Article  CAS  PubMed  Google Scholar 

  260. Falavarjani KG, Parvaresh MM, Shahraki K, Nekoozadeh S, Amirfarhangi A. Central retinal artery occlusion in Crohn disease. J AAPOS. 2012;16(4):392–3.

    Article  PubMed  Google Scholar 

  261. Ernst BB, Lowder CY, Meisler DM, Gutman FA. Posterior segment manifestations of inflammatory bowel disease. Ophthalmology. 1991;98(8):1272–80.

    Article  CAS  PubMed  Google Scholar 

  262. Dutt S, Cartwright MJ, Nelson CC. Acute dacryoadenitis and Crohn’s disease: findings and management. Ophthal Plast Reconstr Surg. 1992;8(4):295–9.

    Article  CAS  PubMed  Google Scholar 

  263. Rafiei N, Tabandeh H, Hirschbein M. Bilateral dacroadenitis associated with acute Crohn’s disease. Eye. 2006;20(12):1372–3.

    Article  CAS  PubMed  Google Scholar 

  264. Satchi K, McNab AA. Lacrimal obstruction in inflammatory bowel disease. Ophthal Plast Reconstr Surg. 2009;25(5):346–9.

    Article  PubMed  Google Scholar 

  265. Greninger DA, Yoon MK, Bloomer MM, Keyser R, Kersten RC. Extraintestinal Crohn disease causing bilateral nasolacrimal duct obstruction. Ophthal Plast Reconstr Surg. 2012;28(2):e55–6.

    Article  PubMed  Google Scholar 

  266. Young RSK, Hodes BL, Cruse RP, Koch KL, Garovoy MR. Orbital pseudotumor and Crohn disease. J Pediatr. 1981;99(2):250–2.

    Article  CAS  PubMed  Google Scholar 

  267. Camfield PR, White M, Warner HA, Lythgoe C. Orbital pseudotumor and Crohn disease. J Pediatr. 1982;101(1):158.

    Article  Google Scholar 

  268. Weinstein JM, Koch K, Lane S. Orbital pseudotumor in Crohn’s colitis. Ann Ophthalmol. 1984;16(3):275–8.

    CAS  PubMed  Google Scholar 

  269. Durno CA, Ehrlich R, Taylor R, Buncic JR, Hughes P, Griffiths AM. Keeping an eye on Crohn’s disease: orbital myositis as the presenting symptom. Can J Gastroenterol. 1997;11(6):497–500.

    Article  CAS  PubMed  Google Scholar 

  270. Degraeuwe PL, Beld MP, Ashorn M, Canani RB, Day AS, Diamanti A, et al. Faecal calprotectin in suspected paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015;60(3):339–46.

    Article  CAS  PubMed  Google Scholar 

  271. Day AS, Lopez RN. Exclusive enteral nutrition in children with Crohn’s disease. World J Gastroenterol. 2015;21(22):6809–16.

    PubMed  PubMed Central  Google Scholar 

  272. Peneau A, Savoye G, Turck D, Dauchet L, Fumery M, Salleron J, et al. Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2013;108(10):1647–53.

    Article  PubMed  Google Scholar 

  273. Burkardt DD, Graham Jr JM, Short SS, Frykman PK. Advances in Hirschsprung disease genetics and treatment strategies: an update for the primary care pediatrician. Clin Pediatr (Phila). 2014;53(1):71–81.

    Article  Google Scholar 

  274. Hirschsprung H. Stuhlträgheit neugeborener in folge von dilatation und hypertrophie des colons. Jahrbuch für Kinderheilkunde und physische Erziehung (Berlin). 1888;27:1–7.

    Google Scholar 

  275. Whitehouse FR, Kernohan JW. Myenteric plexus in congenital megacolon; study of 11 cases. Arch Intern Med (Chic). 1948;82(1):75–111.

    Article  CAS  Google Scholar 

  276. Zuelzer WW, Wilson JL. Neurogenic intestinal obstruction in infancy; a clinical and pathologic study. Am J Dis Child. 1947;73(2):241.

    CAS  PubMed  Google Scholar 

  277. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990;46(3):568–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  278. Chumpitazi BP, Nurko S. Defecation disorders in children after surgery for Hirschsprung disease. J Pediatr Gastroenterol Nutr. 2011;53(1):75–9.

    Article  PubMed  Google Scholar 

  279. Parisi MA. Hirschsprung disease overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle, WA: University of Washington, Seattle; 2011.

    Google Scholar 

  280. Daniels AB, Sandberg MA, Chen J, Weigel-DiFranco C, Fielding Hejtmancic J, Berson EL. Genotype-phenotype correlations in Bardet-Biedl syndrome. Arch Ophthalmol. 2012;130(7):901–7.

    Article  PubMed  Google Scholar 

  281. Goldberg DS, Ludwig IH. Congenital central hypoventilation syndrome: ocular findings in 37 children. J Pediatr Ophthalmol Strabismus. 1996;33(3):175–80.

    CAS  PubMed  Google Scholar 

  282. Gold-von Simson G, Axelrod FB. Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care. 2006;36(6):218–37.

    Article  PubMed  Google Scholar 

  283. Pierson DM, Taboada E, Butler MG. Eye abnormalities in Fryns syndrome. Am J Med Genet A. 2004;125A(3):273–7.

    Article  PubMed  Google Scholar 

  284. Drevillon L, Megarbane A, Demeer B, Matar C, Benit P, Briand-Suleau A, et al. KBP-cytoskeleton interactions underlie developmental anomalies in Goldberg-Shprintzen syndrome. Hum Mol Genet. 2013;22(12):2387–99.

    Article  CAS  PubMed  Google Scholar 

  285. Brooks AS, Breuning MH, Osinga J, vd Smagt JJ, Catsman CE, Buys CH, et al. A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome). J Med Genet. 1999;36(6):485–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  286. Schuffler MD, Bird TD, Sumi SM, Cook A. A familial neuronal disease presenting as intestinal pseudoobstruction. Gastroenterology. 1978;75(5):889–98.

    CAS  PubMed  Google Scholar 

  287. Takai S, Kinoshita S, Tanaka F, Ikeda M, Tanaka N, Kobayashi T. Prominent corneal nerves in patients with multiple endocrine neoplasia type 2A: diagnostic implications. World J Surg. 1992;16(4):620–3. discussion 4.

    Article  CAS  PubMed  Google Scholar 

  288. Lee R, Hyer J, Chowdhury H, Teimory M. Ocular signs of multiple endocrine neoplasia type 2B (MEN2B). J Clin Endocrinol Metab. 2012;97(3):725–6.

    Article  CAS  PubMed  Google Scholar 

  289. Garavelli L, Mainardi PC. Mowat-Wilson syndrome. Orphanet J Rare Dis. 2007;2:42.

    Article  PubMed  PubMed Central  Google Scholar 

  290. Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010;12(1):1–11.

    Article  PubMed  Google Scholar 

  291. Atchaneeyasakul LO, Linck LM, Connor WE, Weleber RG, Steiner RD. Eye findings in 8 children and a spontaneously aborted fetus with RSH/Smith-Lemli-Opitz syndrome. Am J Med Genet. 1998;80(5):501–5.

    Article  CAS  PubMed  Google Scholar 

  292. Toki F, Suzuki N, Inoue K, Suzuki M, Hirakata K, Nagai K, et al. Intestinal aganglionosis associated with the Waardenburg syndrome: report of two cases and review of the literature. Pediatr Surg Int. 2003;19(11):725–8.

    Article  PubMed  Google Scholar 

  293. Mahmoudi A, Rami M, Khattala K, Elmadi A, Afifi MA, Youssef B. Shah-Waardenburg syndrome. Pan Afr Med J. 2013;14:60.

    PubMed  PubMed Central  Google Scholar 

  294. Wang JX, Dahal GR. Hirschsprung’s disease management: from multi staged operation to single staged transanal pull-through. Nepal Med Coll J. 2009;11(2):138–42.

    CAS  PubMed  Google Scholar 

  295. Husby S, Koletzko S, Korponay-Szabo IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–60.

    Article  CAS  PubMed  Google Scholar 

  296. Buysschaert M. Coeliac disease in patients with type 1 diabetes mellitus and auto-immune thyroid disorders. Acta Gastroenterol Belg. 2003;66(3):237–40.

    CAS  PubMed  Google Scholar 

  297. Tran TH. Advances in pediatric celiac disease. Curr Opin Pediatr. 2014;26(5):585–9.

    Article  CAS  PubMed  Google Scholar 

  298. Losowsky MS. A history of coeliac disease. Dig Dis. 2008;26(2):112–20.

    Article  CAS  PubMed  Google Scholar 

  299. Mounajjed T, Oxentenko A, Shmidt E, Smyrk T. The liver in celiac disease: clinical manifestations, histologic features, and response to gluten-free diet in 30 patients. Am J Clin Pathol. 2011;136(1):128–37.

    Article  PubMed  Google Scholar 

  300. Karpati S. Dermatitis herpetiformis. Clin Dermatol. 2012;30(1):56–9.

    Article  PubMed  Google Scholar 

  301. Ludvigsson JF, Ludvigsson J, Ekbom A, Montgomery SM. Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care. 2006;29(11):2483–8.

    Article  PubMed  Google Scholar 

  302. Ch’ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007;5(3):184–92.

    Article  PubMed  PubMed Central  Google Scholar 

  303. Betterle C, Lazzarotto F, Spadaccino AC, Basso D, Plebani M, Pedini B, et al. Celiac disease in North Italian patients with autoimmune Addison’s disease. Eur J Endocrinol. 2006;154(2):275–9.

    Article  CAS  PubMed  Google Scholar 

  304. Hadjivassiliou M, Grunewald R, Sharrack B, Sanders D, Lobo A, Williamson C, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003;126(Pt 3):685–91.

    Article  PubMed  Google Scholar 

  305. Wills AJ, Unsworth DJ. Gluten ataxia ‘in perspective’. Brain. 2003;126(Pt 9), E4; author reply E5.

    Article  PubMed  Google Scholar 

  306. Versino M, Franciotta D, Colnaghi S, Biagi F, Zardini E, Bianchi PI, et al. Cerebellar signs in celiac disease. Neurology. 2009;72(23):2046–8.

    Article  CAS  PubMed  Google Scholar 

  307. Collin P, Pirttila T, Nurmikko T, Somer H, Erila T, Keyrilainen O. Celiac disease, brain atrophy, and dementia. Neurology. 1991;41(3):372–5.

    Article  CAS  PubMed  Google Scholar 

  308. Tolentino P, Spirito L, Jannuzzi C. Celiac syndrome, retinal dystrophy, acanthocytosis, without defect of beta lipoprotein. Ann Paediatr. 1964;203:178–86.

    CAS  PubMed  Google Scholar 

  309. Martinucci M, Conti CA, Calandi C. Severe keratitis due to hypovitaminosis A in a subject with intestinal disease due to glutin. Minerva Pediatr. 1977;29(13):931–4.

    CAS  PubMed  Google Scholar 

  310. Urganci N, Kalyoncu D. Eye disorders in children with celiac disease. Eur J Ophthalmol. 2016;26:85–7.

    Article  PubMed  Google Scholar 

  311. Ruch W, Schurmann K, Gordon P, Burgin-Wolff A, Girard J. Coexistent coeliac disease, Graves’ disease and diabetes mellitus type 1 in a patient with Down syndrome. Eur J Pediatr. 1985;144(1):89–90.

    Article  CAS  PubMed  Google Scholar 

  312. Gora-Gebka M, Wozniak M, Cielecka-Kuszyk J, Korpal-Szczyrska M, Sznurkowska K, Zagierski M, et al. Graves’ disease, Celiac disease and liver function abnormalities in a patient—clinical manifestation and diagnostic difficulties. Acta Biochim Pol. 2014;61(2):281–4.

    PubMed  Google Scholar 

  313. Spadaccino AC, Basso D, Chiarelli S, Albergoni MP, D’Odorico A, Plebani M, et al. Celiac disease in North Italian patients with autoimmune thyroid diseases. Autoimmunity. 2008;41(1):116–21.

    Article  CAS  PubMed  Google Scholar 

  314. Ponto KA, Schuppan D, Zwiener I, Binder H, Mirshahi A, Diana T, et al. Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity. Clin Exp Immunol. 2014;178(1):57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  315. Sandyk R, Brennan MJ. Isolated ocular myopathy and celiac disease in childhood. Neurology. 1983;33(6):792.

    Article  CAS  PubMed  Google Scholar 

  316. Laghmari M, Karim A, Guedira K, Ibrahimy W, Dahreddine M, Essakalli NH, et al. Uveitis in children: about 20 cases. J Fr Ophtalmol. 2003;26(6):609–13.

    CAS  PubMed  Google Scholar 

  317. Al Hemidan AI, Tabbara KF, Althomali T. Vogt-Koyanagi-Harada associated with diabetes mellitus and celiac disease in a 3-year-old girl. Eur J Ophthalmol. 2006;16(1):173–7.

    CAS  PubMed  Google Scholar 

  318. Krifa F, Knani L, Sakly W, Ghedira I, Essoussi AS, Boukadida J, et al. Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1. Gastroenterol Clin Biol. 2010;34(4–5):319–20.

    Article  CAS  PubMed  Google Scholar 

  319. Arikan-Ayyildiz Z, Uslu N, Balamtekin N, Saltik-Temizel IN. Uveitis: a rare presentation finding of celiac disease in childhood. Turk J Pediatr. 2011;53(2):235–6.

    PubMed  Google Scholar 

  320. Mollazadegan K, Kugelberg M, Tallstedt L, Ludvigsson JF. Increased risk of uveitis in coeliac disease: a nationwide cohort study. Br J Ophthalmol. 2012;96(6):857–61.

    Article  PubMed  Google Scholar 

  321. Raina UK, Goel N, Sud R, Thakar M, Ghosh B. Bilateral total cataract as the presenting feature of celiac disease. Int Ophthalmol. 2011;31(1):47–50.

    Article  PubMed  Google Scholar 

  322. Kanwar AJ, Ajith C, Narang T. Cicatricial pemphigoid associated with coeliac disease in a child. J Eur Acad Dermatol Venereol. 2006;20(9):1148–50.

    Article  CAS  PubMed  Google Scholar 

  323. Tuncer S, Yeniad B, Peksayar G. Regression of conjunctival tumor during dietary treatment of celiac disease. Indian J Ophthalmol. 2010;58(5):433–4.

    Article  PubMed  PubMed Central  Google Scholar 

  324. Keskin O, Keskin M, Guler E, Tutar E, Saygili O, Kucukosmanoglu E, et al. Unusual presentation: pulmonary hemosiderosis with celiac disease and retinitis pigmentosa in a child. Pediatr Pulmonol. 2011;46(8):820–3.

    Article  PubMed  Google Scholar 

  325. Mohn A, di Ricco L, Magnelli A, Chiarelli F. Celiac disease—associated vertigo and nystagmus. J Pediatr Gastroenterol Nutr. 2002;34(3):317–18.

    Article  PubMed  Google Scholar 

  326. Deconinck N, Scaillon M, Segers V, Groswasser JJ, Dan B. Opsoclonus-myoclonus associated with celiac disease. Pediatr Neurol. 2006;34(4):312–14.

    Article  PubMed  Google Scholar 

  327. Meyts I, Jansen K, Renard M, Bossuyt X, Roelens F, Regal L, et al. Neuromyelitis optica-IgG+ optic neuritis associated with celiac disease and dysgammaglobulinemia: a role for tacrolimus? Eur J Paediatr Neurol. 2011;15(3):265–7.

    Article  PubMed  Google Scholar 

  328. Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA. Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol. 2010;105(6):1412–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  329. Bannister EG, Cameron DJ, Ng J, Chow CW, Oliver MR, Alex G, et al. Can celiac serology alone be used as a marker of duodenal mucosal recovery in children with celiac disease on a gluten-free diet? Am J Gastroenterol. 2014;109(9):1478–83.

    Article  CAS  PubMed  Google Scholar 

  330. Gottlieb K, Dawson J, Hussain F, Murray JA. Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials. Gastroenterol Rep. 2015;3(2):91–102.

    Article  Google Scholar 

  331. Abu-El-Haija M, Lin TK, Palermo J. Update to the management of pediatric acute pancreatitis: highlighting areas in need of research. J Pediatr Gastroenterol Nutr. 2014;58(6):689–93.

    PubMed  Google Scholar 

  332. Morinville VD, Husain SZ, Bai H, Barth B, Alhosh R, Durie PR, et al. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr. 2012;55(3):261–5.

    Article  PubMed  PubMed Central  Google Scholar 

  333. Ceppa EP, Pitt HA, Hunter JL, Leys CM, Zyromski NJ, Rescorla FJ, et al. Hereditary pancreatitis: endoscopic and surgical management. J Gastrointest Surg. 2013;17(5):847–56. discussion 56–7.

    Article  PubMed  Google Scholar 

  334. Nydegger A, Heine RG, Ranuh R, Gegati-Levy R, Crameri J, Oliver MR. Changing incidence of acute pancreatitis: 10-year experience at the Royal Children’s Hospital. Melbourne J Gastroenterol Hepatol. 2007;22(8):1313–16.

    Article  PubMed  Google Scholar 

  335. Bai HX, Lowe ME, Husain SZ. What have we learned about acute pancreatitis in children? J Pediatr Gastroenterol Nutr. 2011;52(3):262–70.

    Article  PubMed  PubMed Central  Google Scholar 

  336. O’Reilly DA, Kingsnorth AN. A brief history of pancreatitis. J R Soc Med. 2001;94(3):130–2.

    PubMed  PubMed Central  Google Scholar 

  337. Pant C, Deshpande A, Sferra TJ, Gilroy R, Olyaee M. Emergency department visits for acute pancreatitis in children: results from the Nationwide Emergency Department Sample 2006–2011. J Investig Med. 2015;63(4):646–8.

    Article  PubMed  Google Scholar 

  338. Morinville VD, Barmada MM, Lowe ME. Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible? Pancreas. 2010;39(1):5–8.

    Article  PubMed  Google Scholar 

  339. Kramer C, Jeffery A. Pancreatitis in children. Crit Care Nurse. 2014;34(4):43–52. quiz 3.

    Article  PubMed  Google Scholar 

  340. Srinath AI, Lowe ME. Pediatric pancreatitis. Pediatr Rev. 2013;34(2):79–90.

    Article  PubMed  Google Scholar 

  341. Kuhn RJ, Gelrud A, Munck A, Caras S. CREON (Pancrelipase Delayed-Release Capsules) for the treatment of exocrine pancreatic insufficiency. Adv Ther. 2010;27(12):895–916.

    Article  CAS  PubMed  Google Scholar 

  342. Mudumbai RC, Bhandari A. Bilateral isolated lateral geniculate body lesions in a patient with pancreatitis and microangiopathy. J Neuroophthalmol. 2007;27(3):169–75.

    Article  PubMed  Google Scholar 

  343. Miguel AI, Henriques F, Azevedo LF, Loureiro AJ, Maberley DA. Systematic review of Purtscher’s and Purtscher-like retinopathies. Eye. 2013;27(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  344. Basit S, Elsas T, Kvistad KA, Hosoien LS. Wernicke’s encephalopathy because of pancreatitis in a young boy. Acta Ophthalmol. 2011;89(8):e656–7.

    Article  PubMed  Google Scholar 

  345. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1–15.

    Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Royal Children’s Hospital, 50 Flemington Road, Parkville, VIC, 3052, Australia

    James E. Elder MBBS, FRANZCO, FRACS

  2. Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital, 50 Flemington Road, Parkville, VIC, 3052, Australia

    Winita Hardikar M.B.B.S., F.R.A.C.P., Ph.D.

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  1. James E. Elder MBBS, FRANZCO, FRACS
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Correspondence to James E. Elder MBBS, FRANZCO, FRACS .

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  1. Pediatric Ophthalmology and Ocular Genetics Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Alex V. Levin

  2. Department of Ophthalmology, University of Colorado School of Medicine Children’s Hospital Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Robert W. Enzenauer

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Elder, J.E., Hardikar, W. (2017). Ocular Manifestations of Gastrointestinal Disease. In: Levin, A., Enzenauer, R. (eds) The Eye in Pediatric Systemic Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-18389-3_10

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