{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T01:34:24Z","timestamp":1783215264013,"version":"3.54.6"},"reference-count":95,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001322","name":"Medical Research council of South africa","doi-asserted-by":"crossref","award":["SIR grant"],"award-info":[{"award-number":["SIR grant"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Research Foundation of South Africa","award":["incentive grant for rated researchers"],"award-info":[{"award-number":["incentive grant for rated researchers"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Surg Int"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1007\/s00383-018-4344-z","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T08:18:49Z","timestamp":1536913129000},"page":"1127-1137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Advances in understanding the association between Down syndrome and Hirschsprung disease (DS\u2013HSCR)"],"prefix":"10.1007","volume":"34","author":[{"given":"S. W.","family":"Moore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"4344_CR1","unstructured":"World Health Association (2018) WHO\u2019s Human Genomics in Global Health initiative- Downs syndrome. http:\/\/www.who.int\/genomics\/public\/geneticdiseases\/en\/index1.html"},{"key":"4344_CR2","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/00004836-198604000-00002","volume":"8","author":"PJ Buchin","year":"1986","unstructured":"Buchin PJ, Levy JS, Schullinger JN (1986) Down\u2019s syndrome and the gastrointestinal tract. J Clin Gastroenterol 8:111\u2013114","journal-title":"J Clin Gastroenterol"},{"key":"4344_CR3","first-page":"245","volume":"373","author":"J Levy","year":"1991","unstructured":"Levy J (1991) The gastrointestinal tract in Down syndrome. Prog Clin Biol Res 373:245\u2013256","journal-title":"Prog Clin Biol Res"},{"key":"4344_CR4","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/(SICI)1096-8628(19990625)89:2<96::AID-AJMG7>3.0.CO;2-4","volume":"89","author":"JK Spahis","year":"1999","unstructured":"Spahis JK, Wilson GN (1999) Down syndrome: perinatal complications and counseling experiences in 216 patients. Am J Med Genet 89:96\u201399","journal-title":"Am J Med Genet"},{"key":"4344_CR5","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/(SICI)1096-8628(19961016)65:2<160::AID-AJMG16>3.0.CO;2-O","volume":"65","author":"B Kallen","year":"1996","unstructured":"Kallen B, Mastroiacovo P, Robert E (1996) Major congenital malformations in Down syndrome. Am J Med Genet 65:160\u2013166","journal-title":"Am J Med Genet"},{"key":"4344_CR6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1080\/13668250601146761","volume":"32","author":"RA Wallace","year":"2007","unstructured":"Wallace RA (2007) Clinical audit of gastrointestinal conditions occurring among adults with Down syndrome attending a specialist clinic. J Intellect Dev Disabil 32:45\u201350","journal-title":"J Intellect Dev Disabil"},{"key":"4344_CR7","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1002\/ppul.20687","volume":"42","author":"K Weir","year":"2007","unstructured":"Weir K, McMahon S, Barry L, Ware R, Masters IB, Chang AB (2007) Oropharyngeal aspiration and pneumonia in children. Pediatr Pulmonol 42:1024\u20131031","journal-title":"Pediatr Pulmonol"},{"key":"4344_CR8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.33588\/rn.4512.2007256","volume":"45","author":"MC Carrascosa-Romero","year":"2007","unstructured":"Carrascosa-Romero MC, Fernandez-Cordoba MS, Gonzalvez-Pinera J, Gutierrez-Junquera C, Pardal-Fernandez JM (2007) Neurocristopathies: a high incidence of cerebral dysgenesis in patients with Hirschsprung\u2019s disease. Rev Neurol 45:707\u2013712","journal-title":"Rev Neurol"},{"key":"4344_CR9","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s00383-010-2807-y","volume":"27","author":"SW Moore","year":"2011","unstructured":"Moore SW (2011) Hirschsprung\u2019s disease and the brain. Pediatr Surg Int 27:347\u2013352","journal-title":"Pediatr Surg Int"},{"key":"4344_CR10","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1056\/NEJM196701192760303","volume":"276","author":"E Passarge","year":"1967","unstructured":"Passarge E (1967) The genetics of Hirschsprungs disease. N Engl J Med 276:138\u2013143","journal-title":"N Engl J Med"},{"key":"4344_CR11","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1399-0004.1985.tb00417.x","volume":"28","author":"K Garver","year":"1985","unstructured":"Garver K, Law J, Garver B (1985) Hirschsprung disease: a genetic study. Clin Genet 28:503\u2013508","journal-title":"Clin Genet"},{"key":"4344_CR12","first-page":"279","volume":"41","author":"K Ikeda","year":"1986","unstructured":"Ikeda K, Goto S (1986) Additional anomalies in Hirschsprungs disease: an analysis based on a nationwide survey in Japan. Z Kinderchir 41:279\u2013281","journal-title":"Z Kinderchir"},{"key":"4344_CR13","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/tera.1420320204","volume":"32","author":"D Spouge","year":"1985","unstructured":"Spouge D, Baird PA (1985) Hirschsprungs Disease in a large birth cohort. Teratology 32:171\u2013177","journal-title":"Teratology"},{"key":"4344_CR14","first-page":"568","volume":"46","author":"JA Badner","year":"1990","unstructured":"Badner JA, Sieber WK, Garver KL, Chakravarti A (1990) A genetic study of Hirschsprung disease. Am J Hum Genet 46:568\u2013580","journal-title":"Am J Hum Genet"},{"key":"4344_CR15","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1002\/humu.20944","volume":"30","author":"S Arnold","year":"2009","unstructured":"Arnold S, Pelet A, Amiel J, Borrego S, Hofstra R, Tam P, Ceccherini I, Lyonnet S, Sherman S, Chakravarti A (2009) Interaction between a chromosome 10 RET enhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association. Hum Mutat 30:771\u2013775","journal-title":"Hum Mutat"},{"key":"4344_CR16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.jpedsurg.2011.11.018","volume":"47","author":"SW Moore","year":"2012","unstructured":"Moore SW, Zaahl MG (2012) Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population. J Pediatr Surg 47:299\u2013302","journal-title":"J Pediatr Surg"},{"key":"4344_CR17","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1073\/pnas.97.1.268","volume":"97","author":"S Bolk","year":"2000","unstructured":"Bolk S, Pelet A, Hofstra RM, Angrist M, Salomon R, Croaker D, Buys CH, Lyonnet S, Chakravarti A (2000) A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. Proc Natl Acad Sci U S A 97:268\u2013273","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4344_CR18","first-page":"458","volume":"60","author":"L Graivier","year":"1966","unstructured":"Graivier L, Sieber WK (1966) Hirschsprungs disease and mongolism. Surgery 60:458\u2013461","journal-title":"Surgery"},{"key":"4344_CR19","first-page":"937","volume":"29","author":"F Friedmacher","year":"2013","unstructured":"Friedmacher F, Puri P (2013) Hirschsprung\u2019s disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality. PediatrSurgInt 29:937\u2013946","journal-title":"PediatrSurgInt"},{"key":"4344_CR20","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1016\/j.jpedsurg.2009.07.055","volume":"44","author":"S Ieiri","year":"2009","unstructured":"Ieiri S, Higashi M, Teshiba R, Saeki I, Esumi G, Akiyoshi J, Nakatsuji T, Taguchi T (2009) Clinical features of Hirschsprung\u2019s disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan. J Pediatr Surg 44:2347\u20132351","journal-title":"J Pediatr Surg"},{"key":"4344_CR21","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1093\/hmg\/3.8.1217","volume":"3","author":"E Puffenberger","year":"1994","unstructured":"Puffenberger E, Kauffman E, Bolk S et al (1994) Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet 3:1217\u20131225","journal-title":"Hum Mol Genet"},{"key":"4344_CR22","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/ajmg.c.20003","volume":"121C","author":"EG Puffenberger","year":"2003","unstructured":"Puffenberger EG (2003) Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. Am J Med Genet 121C:18\u201331","journal-title":"Am J Med Genet"},{"key":"4344_CR23","first-page":"793","volume":"6","author":"JC Li","year":"2000","unstructured":"Li JC, Busch L, Kuhnel W (2000) Immunohistochemical study on gastroenteric nervous system in trisomy 16 mice:an animal model of Down syndrome. World JGastroenterol 6:793\u2013799","journal-title":"World JGastroenterol"},{"key":"4344_CR24","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1097\/00000658-198803000-00003","volume":"207","author":"DH Teitelbaum","year":"1988","unstructured":"Teitelbaum DH, Qualman SJ, Caniano DA (1988) Hirschsprungs disease: Identification of risk factors for enterocolitis. Ann Surg 207:240\u2013244","journal-title":"Ann Surg"},{"key":"4344_CR25","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00383-005-1617-0","volume":"22","author":"A Morabito","year":"2006","unstructured":"Morabito A, Lall A, Gull S, Mohee A, Bianchi A (2006) The impact of Down\u2019s syndrome on the immediate and long-term outcomes of children with Hirschsprung\u2019s disease. Pediatr Surg Int 22:179\u2013181","journal-title":"Pediatr Surg Int"},{"key":"4344_CR26","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/S1055-8586(98)70011-3","volume":"7","author":"SW Moore","year":"1998","unstructured":"Moore SW, Johnson GA (1998) Hirschsprungs disease: genetic and functional associations of Downs and Waardenburghs syndromes. Semin Pediatr Surg (USA) 7:156\u2013161","journal-title":"Semin Pediatr Surg (USA)"},{"key":"4344_CR27","first-page":"185","volume":"33","author":"WD Wilson-Storey","year":"1988","unstructured":"Wilson-Storey WD, Scobie WG, Raeburn JA (1988) Defective white blood cell function in Hirschsprungs disease: a possible predisposing factor for enterocolitis. J R Coll Surg Edinb 33:185\u2013188","journal-title":"J R Coll Surg Edinb"},{"key":"4344_CR28","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.jpedsurg.2007.12.057","volume":"43","author":"SW Moore","year":"2008","unstructured":"Moore SW, Sidler D, Zaahl MG (2008) The ITGB2 immunomodulatory gene (CD18), enterocolitis, and Hirschsprungs disease. J Pediatr Surg 43:1439\u20131444","journal-title":"J Pediatr Surg"},{"key":"4344_CR29","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ydbio.2016.03.017","volume":"417","author":"RO Heuckeroth","year":"2016","unstructured":"Heuckeroth RO, Schafer KH (2016) Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention. Dev Biol 417:188\u2013197","journal-title":"Dev Biol"},{"key":"4344_CR30","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1136\/jmg.38.9.646","volume":"38","author":"JP Boardman","year":"2001","unstructured":"Boardman JP, Syrris P, Holder SE, Robertson NJ, Carter N, Lakhoo K (2001) A novel mutation in the endothelin B receptor gene in a patient with Shah-Waardenburg syndrome and Down syndrome. J Med Genet 38:646\u2013647","journal-title":"J Med Genet"},{"key":"4344_CR31","first-page":"2519","volume":"21","author":"AS Karlsen","year":"2011","unstructured":"Karlsen AS, Pakkenberg B (2011) Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome\u2014a stereological study. CerebCortex 21:2519\u20132524","journal-title":"CerebCortex"},{"key":"4344_CR32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3109\/15513818609068848","volume":"5","author":"Y Nakazato","year":"1986","unstructured":"Nakazato Y, Landing BH (1986) Reduced number of neurons in esophageal plexus ganglia in Down syndrome: additional evidence for reduced cell number as a basic feature of the disorder. Pediatr Pathol 5:55\u201363","journal-title":"Pediatr Pathol"},{"key":"4344_CR33","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/(SICI)1096-8628(19981228)80:5<518::AID-AJMG16>3.0.CO;2-M","volume":"80","author":"A Mathew","year":"1998","unstructured":"Mathew A (1998) Anencephaly-associated aganglionosis. Am J Med Genet 80:518\u2013520","journal-title":"Am J Med Genet"},{"key":"4344_CR34","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1055\/s-2008-1072288","volume":"9","author":"A Leffler","year":"1999","unstructured":"Leffler A, Wedel T, Busch LC (1999) Congenital colonic hypoganglionosis in murine trisomy 16\u2014an animal model for Down\u2019s syndrome. Eur J Pediatr Surg 9:381\u2013388","journal-title":"Eur J Pediatr Surg"},{"key":"4344_CR35","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1002\/ana.410200413","volume":"20","author":"LE Becker","year":"1986","unstructured":"Becker LE, Armstrong DL, Chan F (1986) Dendritic atrophy in children with Down\u2019s syndrome. Ann Neurol 20:520\u2013526","journal-title":"Ann Neurol"},{"key":"4344_CR36","doi-asserted-by":"publisher","first-page":"e78561","DOI":"10.1371\/journal.pone.0078561","volume":"8","author":"MA Haas","year":"2013","unstructured":"Haas MA, Bell D, Slender A, Lana-Elola E, Watson-Scales S, Fisher MC et al (2013) Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome. PLoS One 8:e78561\u2013e78561M:24205261","journal-title":"PLoS One"},{"key":"4344_CR37","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1093\/jnen\/63.7.679","volume":"63","author":"RE Mrak","year":"2004","unstructured":"Mrak RE, Griffin WS (2004) Trisomy 21 and the brain. J Neuropathol Exp Neurol 63:679\u2013685","journal-title":"J Neuropathol Exp Neurol"},{"key":"4344_CR38","doi-asserted-by":"publisher","first-page":"4430","DOI":"10.1038\/ncomms5430","volume":"5","author":"C Chen","year":"2014","unstructured":"Chen C, Jiang P, Xue H, Peterson SE, Tran HT, McCann AE et al (2014) Role of astroglia in Down\u2019s syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat Commun 5:4430","journal-title":"Nat Commun"},{"key":"4344_CR39","doi-asserted-by":"publisher","first-page":"471","DOI":"10.4067\/S0716-97602006000300009","volume":"39","author":"P Caviedes","year":"2006","unstructured":"Caviedes P, Caviedes R, Rapoport SI (2006) Altered calcium currents in cultured sensory neurons of normal and trisomy 16 mouse fetuses, an animal model for human trisomy 21 (Down syndrome). Biol Res 39:471\u2013481","journal-title":"Biol Res"},{"key":"4344_CR40","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jphysparis.2005.12.013","volume":"99","author":"K Saud","year":"2006","unstructured":"Saud K, Arriagada C, Cardenas AM, Shimahara T, Allen DD, Caviedes R, Caviedes P (2006) Neuronal dysfunction in Down syndrome: contribution of neuronal models in cell culture. J Physiol Paris 99:201\u2013210","journal-title":"J Physiol Paris"},{"key":"4344_CR41","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.cell.2004.12.020","volume":"120","author":"KS Christopherson","year":"2005","unstructured":"Christopherson KS, Ullian EM, Stokes CC, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120:421\u2013433","journal-title":"Cell"},{"key":"4344_CR42","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/glia.20082","volume":"47","author":"EM Ullian","year":"2004","unstructured":"Ullian EM, Christopherson KS, Barres BA, (2004) Role for glia in synaptogenesis. Glia 47:209\u2013216","journal-title":"Glia"},{"key":"4344_CR43","doi-asserted-by":"publisher","first-page":"31884","DOI":"10.1074\/jbc.M801316200","volume":"283","author":"M Guizzetti","year":"2008","unstructured":"Guizzetti M, Moore NH, Giordano G, Costa LG (2008) Modulation of neuritogenesis by astrocyte muscarinic receptors. J Biol Chem 283:31884\u201331897","journal-title":"J Biol Chem"},{"key":"4344_CR44","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1093\/hmg\/4.5.821","volume":"4","author":"M Angrist","year":"1995","unstructured":"Angrist M, Bolk S, Thiel B, Puffenberger EG, Hofstra RM, Buys CH, Cass DT, Chakravarti A (1995) Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. Hum Mol Genet 4:821\u2013830","journal-title":"Hum Mol Genet"},{"key":"4344_CR45","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.ydbio.2013.05.019","volume":"382","author":"MM Alves","year":"2013","unstructured":"Alves MM, Sribudiani Y, Brouwer RW, Amiel J, Antinolo G, Borrego S, Ceccherini I et al (2013) Contribution of rare and common variants determine complex diseases-Hirschsprung disease as a model. Dev Biol 382:320\u2013329","journal-title":"Dev Biol"},{"key":"4344_CR46","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1093\/hmg\/ddv051","volume":"24","author":"A Kapoor","year":"2015","unstructured":"Kapoor A, Jiang Q, Chatterjee S, Chakraborty P, Sosa MX, Berrios C, Chakravarti A (2015) Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms. Hum Mol Genet 24:2997\u20133003","journal-title":"Hum Mol Genet"},{"key":"4344_CR47","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1136\/jmg.2005.040113","volume":"43","author":"L Pontual de","year":"2006","unstructured":"de Pontual L, Pelet A, Trochet D, Jaubert F, Espinosa-Parrilla Y, Munnich A et al (2006) Mutations of the RET gene in isolated and syndromic Hirschsprung\u2019s disease in human disclose major and modifier alleles at a single locus. J Med Genet 43:419\u2013423","journal-title":"J Med Genet"},{"key":"4344_CR48","doi-asserted-by":"publisher","first-page":"e16181","DOI":"10.1371\/journal.pone.0016181","volume":"6","author":"CS Tang","year":"2011","unstructured":"Tang CS, Tang WK, So MT, Miao XP, Leung BM, Yip BH (2011) Fine mapping of the NRG1 Hirschsprung\u2019s disease locus. PLoSONE 6:e16181","journal-title":"PLoSONE"},{"key":"4344_CR49","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.ajhg.2015.02.014","volume":"96","author":"Q Jiang","year":"2015","unstructured":"Jiang Q, Arnold S, Heanue T, Kilambi KP, Doan B, Kapoor A, Ling AY, Sosa MX, Guy M, Jiang Q, Burzynski G, West K, Bessling S, Griseri P, Amiel J, Fernandez RM, Verheij JB, Hofstra RM, Borrego S, Lyonnet S, Ceccherini I, Gray JJ, Pachnis V, McCallion AS, Chakravarti A et al (2015) Functional loss of semaphorin 3C and\/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. Am J Hum Genet 96:581\u2013596","journal-title":"Am J Hum Genet"},{"key":"4344_CR50","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/nature03467","volume":"434","author":"ES Emison","year":"2005","unstructured":"Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED, Chakravarti A (2005) A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434:857\u2013863","journal-title":"Nature"},{"key":"4344_CR51","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00383-006-1655-2","volume":"22","author":"SW Moore","year":"2006","unstructured":"Moore SW (2006) The contribution of associated congenital anomalies in understanding Hirschsprung\u2019s disease. Pediatr Surg Int 22:305\u2013315","journal-title":"Pediatr Surg Int"},{"key":"4344_CR52","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/sj.ejhg.5200650","volume":"9","author":"MG Julies","year":"2001","unstructured":"Julies MG, Moore SW, Kotze MJ, du Plessis L (2001) Novel RET mutations in Hirschsprung\u2019s disease patients from the diverse South African population. Eur J Hum Genet 9:419\u2013423","journal-title":"Eur J Hum Genet"},{"key":"4344_CR53","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0890-8508(03)00003-3","volume":"17","author":"MG Zaahl","year":"2003","unstructured":"Zaahl MG, du Plessis L, Warnich L, Kotze MJ, Moore SW (2003) Significance of novel endothelin-B receptor gene polymorphisms in Hirschsprung\u2019s disease: predominance of a novel variant (561C\/T) in patients with co-existing Down\u2019s syndrome. Mol Cell Probes 17:49\u201354","journal-title":"Mol Cell Probes"},{"key":"4344_CR54","first-page":"39","volume":"12","author":"A Sanchez-Mejias","year":"2010","unstructured":"Sanchez-Mejias A, Fernandez RM, Lopez-Alonso M, Antinolo G, Borrego S (2010) New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. GenetMed 12:39\u201343","journal-title":"GenetMed"},{"key":"4344_CR55","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1620\/tjem.187.43","volume":"187","author":"T Sakai","year":"1999","unstructured":"Sakai T, Wakizaka A, Nirasawa Y, Ito Y (1999) Point nucleotidic changes in both the RET proto-oncogene and the endothelin-B receptor gene in a Hirschsprung disease patient associated with Down syndrome. Tohoku J Exp Med 187:43\u201347","journal-title":"Tohoku J Exp Med"},{"key":"4344_CR56","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1073\/pnas.0813248106","volume":"106","author":"JO Korbel","year":"2009","unstructured":"Korbel JO, Tirosh-Wagner T, Urban AE, Chen XN, Kasowski M, Dai L et al (2009) The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci USA 106:12031\u201312036","journal-title":"Proc Natl Acad Sci USA"},{"key":"4344_CR57","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1016\/0092-8674(94)90016-7","volume":"79","author":"EG Puffenberger","year":"1994","unstructured":"Puffenberger EG, Hosoda K, Washington SS, Nakao K, deWit D, Yanagisawa M, Chakravart A (1994) A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung\u2019s disease. Cell 79:1256\u20131266","journal-title":"Cell"},{"key":"4344_CR58","doi-asserted-by":"publisher","first-page":"e62519","DOI":"10.1371\/journal.pone.0062519","volume":"8","author":"AS Jannot","year":"2013","unstructured":"Jannot AS, Pelet A, Henrion-Caude A, Chaoui A, Masse-Morel M, Arnold S et al (2013) Chromosome 21 scan in Down syndrome reveals DSCAM as a predisposing locus in Hirschsprung disease. PLoSOne 8:e62519","journal-title":"PLoSOne"},{"key":"4344_CR59","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s10528-010-9333-4","volume":"48","author":"CP Liu","year":"2010","unstructured":"Liu CP, Tang QQ, Lou JT, Luo CF, Zhou XW, Li DM, Chen F, Li X, Li JC (2010) Association analysis of the RET proto-oncogene with Hirschsprung disease in the Han Chinese population of southeastern China. Biochem Genet 48:496\u2013503","journal-title":"Biochem Genet"},{"key":"4344_CR60","first-page":"1","volume":"62","author":"J Baumann","year":"2007","unstructured":"Baumann J (2007) Down syndrome cell adhesion molecule\u2014a common determinant of brain and heart wiring. PediatrRes 62:1","journal-title":"PediatrRes"},{"key":"4344_CR61","first-page":"1422","volume":"20","author":"GB Andrade de","year":"2014","unstructured":"de Andrade GB, Kunzelman L, Merrill MM, Fuerst PG (2014) Developmentally dynamic colocalization patterns of DSCAM with adhesion and synaptic proteins in the mouse retina. MolVis 20:1422\u20131433","journal-title":"MolVis"},{"key":"4344_CR62","unstructured":"Cheng W (2018) ATP50 on human chromosome 21 as a potntial link between Hirschsprung disease and Down syndrome. poster 15 5th International symposium on development of the enteric nervous system.Boston, USA April 8\u201311 2018"},{"key":"4344_CR63","doi-asserted-by":"publisher","first-page":"5764","DOI":"10.1523\/JNEUROSCI.6015-10.2011","volume":"31","author":"M Blank","year":"2011","unstructured":"Blank M, Fuerst PG, Stevens B, Nouri N, Kirkby L, Warrier D et al (2011) The Down syndrome critical region regulates retinogeniculate refinement. JNeurosci 31:5764\u20135776","journal-title":"JNeurosci"},{"key":"4344_CR64","first-page":"258","volume":"49","author":"SW Moore","year":"2014","unstructured":"Moore SW, Zaahl MG (2014) Tissue specific somatic mutations and aganglionosis in Hirschsprung\u2019s disease. J PediatrSurg 49:258\u2013261","journal-title":"J PediatrSurg"},{"key":"4344_CR65","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1111\/febs.12220","volume":"280","author":"E Karousou","year":"2013","unstructured":"Karousou E, Stachtea X, Moretto P, Viola M, Vigetti D, D\u2019Angelo ML et al (2013) New insights into the pathobiology of Down syndrome\u2013hyaluronan synthase-2 overexpression is regulated by collagen VI alpha2 chain. FEBS J 280:2418\u20132430","journal-title":"FEBS J"},{"key":"4344_CR66","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s004290050123","volume":"197","author":"CS Kaisenberg von","year":"1998","unstructured":"von Kaisenberg CS, Krenn V, Ludwig M, Nicolaides KH, Brand-Saberi B (1998) Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12\u201318 weeks and in a trisomy 16 mouse. Anat Embryol (Berl) 197:105\u2013124","journal-title":"Anat Embryol (Berl)"},{"key":"4344_CR67","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/jnr.490320216","volume":"32","author":"S Murtomaki","year":"1992","unstructured":"Murtomaki S, Risteli J, Risteli L, Koivisto UM, Johansson S, Liesi P (1992) Laminin and its neurite outgrowth-promoting domain in the brain in Alzheimer\u2019s disease and Down\u2019s syndrome patients. J Neurosci Res 32:261\u2013273","journal-title":"J Neurosci Res"},{"key":"4344_CR68","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1016\/0016-5085(92)90761-M","volume":"102","author":"DH Parikh","year":"1992","unstructured":"Parikh DH, Tam PK, Van VD, Edgar D (1992) Abnormalities in the distribution of laminin and collagen type IV in Hirschsprung\u2019s disease. Gastroenterology 102:1236\u20131241","journal-title":"Gastroenterology"},{"key":"4344_CR69","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1006\/dbio.1993.1264","volume":"159","author":"TP Rothman","year":"1993","unstructured":"Rothman TP, Goldowitz D, Gershon MD (1993) Inhibition of migration of neural crest-derived cells by the abnormal mesenchyme of the presumptive aganglionic bowel of ls\/ls mice: analysis with aggregation and interspecies chimeras. Dev Biol 159:559\u2013573","journal-title":"Dev Biol"},{"key":"4344_CR70","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1073\/pnas.81.8.2426","volume":"81","author":"TC Wright","year":"1984","unstructured":"Wright TC, Orkin RW, Destrempes M, Kurnit D (1984) Increased adhesiveness of Down syndrome fetal fibroblasts in vitro. Proc Natl Acad Sci USA 81:2426\u20132430","journal-title":"Proc Natl Acad Sci USA"},{"key":"4344_CR71","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1002\/(SICI)1097-4695(199708)33:2<118::AID-NEU2>3.0.CO;2-5","volume":"33","author":"A Chalazonitis","year":"1997","unstructured":"Chalazonitis A, Tennyson VM, Kibbey MC, Rothman TP, Gershon MD (1997) The alpha1 subunit of laminin-1 promotes the development of neurons by interacting with LBP110 expressed by neural crest-derived cells immunoselected from the fetal mouse gut. J Neurobiol 33:118\u2013138","journal-title":"J Neurobiol"},{"key":"4344_CR72","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1046\/j.1440-1681.1999.03176.x","volume":"26","author":"MD Gershon","year":"1999","unstructured":"Gershon MD (1999) Endothelin and the development of the enteric nervous system. Clin Exp Pharmacol Physiol 26:985\u2013988","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"4344_CR73","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00383-003-1035-0","volume":"19","author":"BJ Meyrat","year":"2003","unstructured":"Meyrat BJ, Laurini RN (2003) Plasticity of the enteric nervous system in patients with intestinal neuronal dysplasia associated with Hirschsprung\u2019s disease: a report of three patients. Pediatr Surg Int 19:715\u2013720","journal-title":"Pediatr Surg Int"},{"key":"4344_CR74","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/ajmg.1320200222","volume":"20","author":"DM Kurnit","year":"1985","unstructured":"Kurnit DM, Aldridge JF, Matsuoka R, Matthysse S (1985) Increased adhesiveness of trisomy 21 cells and atrioventricular canal malformations in Down syndrome: a stochastic model. AmJ Med Genet 20:385\u2013399","journal-title":"AmJ Med Genet"},{"key":"4344_CR75","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/ajmg.10413","volume":"109","author":"IN Jongewaard","year":"2002","unstructured":"Jongewaard IN, Lauer RM, Behrendt DA, Patil S, Klewer SE (2002) Beta 1 integrin activation mediates adhesive differences between trisomy 21 and non-trisomic fibroblasts on type VI collagen. Am J Med Genet 109:298\u2013305","journal-title":"Am J Med Genet"},{"key":"4344_CR76","doi-asserted-by":"publisher","first-page":"PM:29678817","DOI":"10.1242\/dev.160317","volume":"145","author":"N Nagy","year":"2018","unstructured":"Nagy N, Barad C, Hotta R, Bhave S, Arciero E, Dora D, Goldstein AM (2018) Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development. Development 145:PM:29678817","journal-title":"Development"},{"key":"4344_CR77","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/gim.2017.178","volume":"20","author":"Q Jiang","year":"2018","unstructured":"Jiang Q, Liu F, Miao C, Li Q, Zhang Z, Xiao P et al (2018) RET somatic mutations are underrecognized in Hirschsprung disease. Genet Med 20:770\u2013777","journal-title":"Genet Med"},{"key":"4344_CR78","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.6","author":"E Brosens","year":"2018","unstructured":"Brosens E, MacKenzie KC, Alves MM, Hofstra RMW (2018) Do RET somatic mutations play a role in Hirschsprung disease? Genet Med. https:\/\/doi.org\/10.1038\/gim.2018.6","journal-title":"Genet Med"},{"key":"4344_CR79","doi-asserted-by":"publisher","first-page":"e0154108","DOI":"10.1371\/journal.pone.0154108","volume":"11","author":"AF Alves da Silva","year":"2016","unstructured":"Alves da Silva AF, Machado FB, Pavarino EC, Biselli-Perico JM, Zampieri BL, da Silva Francisco Junior R, et al (2016) Trisomy 21 alters DNA methylation in parent-of-origin-dependent and -independent manners. PLoS One 11:e0154108","journal-title":"PLoS One"},{"key":"4344_CR80","doi-asserted-by":"publisher","first-page":"e0135555","DOI":"10.1371\/journal.pone.0135555","volume":"10","author":"MR Sailani","year":"2015","unstructured":"Sailani MR, Santoni FA, Letourneau A, Borel C, Makrythanasis P, Hibaoui Y et al (2015) DNA-methylation patterns in trisomy 21 using cells from monozygotic twins. PLoS One 10:e0135555","journal-title":"PLoS One"},{"key":"4344_CR81","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1136\/jmg.38.11.729","volume":"38","author":"J Amiel","year":"2001","unstructured":"Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38:729\u2013739","journal-title":"J Med Genet"},{"key":"4344_CR82","unstructured":"Moore SW, Zaahl M (2006) Immunomodulatory genes, enterocolitis and Hirschsprungs disease (HSCR). Abstract 013: British Association of Paediatric Surgeons Stockholm 19\u201321 July, 2006"},{"key":"4344_CR83","first-page":"236","volume":"47","author":"JR Korenberg","year":"1990","unstructured":"Korenberg JR, Kawashima H, Pulst SM, Ikeuchi T, Ogasawara N, Yamamoto K et al (1990) Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. AmJ Hum Genet 47:236\u2013246","journal-title":"AmJ Hum Genet"},{"key":"4344_CR84","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1385\/BTER:81:1:21","volume":"81","author":"NA Meguid","year":"2001","unstructured":"Meguid NA, Kholoussi NM, Afifi HH (2001) Evaluation of superoxide dismutase and glutathione peroxidase enzymes and their cofactors in Egyptian children with Down\u2019s syndrome. Biol Trace Elem Res 81:21\u201328","journal-title":"Biol Trace Elem Res"},{"key":"4344_CR85","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/s00383-005-1528-0","volume":"21","author":"M Okawada","year":"2005","unstructured":"Okawada M, Okazaki T, Yamataka A, Lane GJ, Miyano T (2005) Down\u2019s syndrome and esophageal achalasia: a rare but important clinical entity. Pediatr Surg Int 21:997\u20131000","journal-title":"Pediatr Surg Int"},{"key":"4344_CR86","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nature04678","volume":"441","author":"JR Arron","year":"2006","unstructured":"Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, Neilson JR et al (2006) NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 441:595\u2013600","journal-title":"Nature"},{"key":"4344_CR87","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/441582a","volume":"44","author":"CJ Epstein","year":"2006","unstructured":"Epstein CJ (2006) Down\u2019s syndrome: critical genes in a critical region. Nature 44:582\u2013583","journal-title":"Nature"},{"key":"4344_CR88","first-page":"218","volume":"52","author":"SW Moore","year":"2017","unstructured":"Moore SW (2017) Genetic impact on the treatment & management of Hirschsprung disease. J PediatrSurg 52:218\u2013222 :.PM:28003043","journal-title":"J PediatrSurg"},{"key":"4344_CR89","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1086\/429589","volume":"76","author":"GM Burzynski","year":"2005","unstructured":"Burzynski GM, Nolte IM, Bronda A, Bos KK, Osinga J, Plaza Menacho I, Twigt B et al (2005) Identifying candidate Hirschsprung disease-associated RET variants. Am J Hum Genet 76:850\u2013858","journal-title":"Am J Hum Genet"},{"key":"4344_CR90","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/ng998","volume":"32","author":"MM Carrasquillo","year":"2002","unstructured":"Carrasquillo MM, McCallion AS, Puffenberger EG, Kaschuk CS, No N, Chakravarti A (2002) Genome-wide association study as well as the study of mouse models help to identify the interaction between RET and EDNRB pathways in Hirschsprung disease. Nat Genet 32:237\u2013244","journal-title":"Nat Genet"},{"key":"4344_CR91","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1001\/archsurg.1978.01370160112019","volume":"113","author":"J Grosfeld","year":"1978","unstructured":"Grosfeld J, Ballantine T, Csicsko J (1978) A critical evaluation of the Duhamel operation for HSCR. Arch Surg 113:454\u2013459","journal-title":"Arch Surg"},{"key":"4344_CR92","first-page":"473","volume":"27","author":"PA Pini","year":"2011","unstructured":"Pini PA, Rossi V, Avanzini S, Mattioli G, Disma N, Jasonni V (2011) Hirschsprung\u2019s disease: what about mortality? PediatrSurgInt 27:473\u2013478","journal-title":"PediatrSurgInt"},{"key":"4344_CR93","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1111\/j.1440-1746.2005.03996.x","volume":"21","author":"AG Catto-Smith","year":"2006","unstructured":"Catto-Smith AG, Trajanovska M, Taylor RG (2006) Long-term continence in patients with Hirschsprung\u2019s disease and Down syndrome. J Gastroenterol Hepatol 21:748\u2013753","journal-title":"J Gastroenterol Hepatol"},{"key":"4344_CR94","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/S0002-9610(05)81281-4","volume":"159","author":"DA Caniano","year":"1990","unstructured":"Caniano DA, Teitelbaum DH, Qualman SJ (1990) Management of Hirschsprungs disease in children with Trisomy 21. Am J Surg 159:402\u2013404","journal-title":"Am J Surg"},{"key":"4344_CR95","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/0022-3468(94)90369-7","volume":"29","author":"FM Quinn","year":"1994","unstructured":"Quinn FM, Surana R, Puri P (1994) The influence of trisomy 21 on outcome in children with Hirschsprung\u2019s disease. Pediatr Surg 29:781\u2013783","journal-title":"Pediatr Surg"}],"container-title":["Pediatric Surgery International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00383-018-4344-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00383-018-4344-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00383-018-4344-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:08:53Z","timestamp":1751875733000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00383-018-4344-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,14]]},"references-count":95,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["4344"],"URL":"https:\/\/doi.org\/10.1007\/s00383-018-4344-z","relation":{},"ISSN":["0179-0358","1437-9813"],"issn-type":[{"value":"0179-0358","type":"print"},{"value":"1437-9813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,14]]},"assertion":[{"value":"10 September 2018","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2018","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"I have no potential conflicts of interest. Grant support for this research was from the Medical Research Council of South Africa Self initiated research (SIR) grant and the National Research Foundation of South Africa (Incentive grant for rated researchers).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This is a review article, but there is some reporting on research involving human participants from published reports. This article does not contain any studies with animals performed by any of the authors.\u2019","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants"}},{"value":"All patients within our reported study had a signed informed consent as indicated in the relevant publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}