{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:52:35Z","timestamp":1791219155361,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["1\/0086\/17"],"award-info":[{"award-number":["1\/0086\/17"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Hirschsprung\u2019s disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut aganglionosis. It usually manifests rapidly after birth, affecting 1 in 5000 live births around the globe. In recent decades, there has been a significant improvement in the understanding of its genetics and the association with other congenital anomalies, which share the pathomechanism of improper development of the neural crest. Apart from that, several cell populations which do not originate from the neural crest, but contribute to the development of Hirschsprung\u2019s disease, have also been described, namely mast cells and interstitial cells of Cajal. From the diagnostic perspective, researchers also focused on \u201cVariants of Hirschsprung\u2019s disease\u201d, which can mimic the clinical signs of the disease, but are in fact different entities, with distinct prognosis and treatment approaches. The treatment of Hirschsprung\u2019s disease is usually surgical resection of the aganglionic part of the intestine, however, as many as 30\u201350% of patients experience persisting symptoms. Considering this fact, this review article also outlines future hopes and perspectives in Hirschsprung\u2019s disease management, which has the potential to benefit from the advancements in the fields of cell-based therapy and tissue engineering.<\/jats:p>","DOI":"10.3390\/medicina56110611","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T10:32:47Z","timestamp":1605263567000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Hirschsprung\u2019s Disease\u2014Recent Understanding of Embryonic Aspects, Etiopathogenesis and Future Treatment Avenues"],"prefix":"10.3390","volume":"56","author":[{"given":"Martin","family":"Klein","sequence":"first","affiliation":[{"name":"Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Spitalska Street 24, SK-813 72 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Varga","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Faculty of Medicine, Comenius University in Bratislava, Spitalska Street 24, SK-813 72 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"ref_1","unstructured":"FIPAT (2017). Terminologia Embryologica, Federative International Programme for Anatomical Terminology. [2nd ed.]. Available online: https:\/\/fipat.library.dal.ca\/TE2\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ydbio.2016.06.017","article-title":"Epigenetics in ENS development and Hirschsprung disease","volume":"417","author":"Torroglosa","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1136\/archdischild-2016-311872","article-title":"British Association of Paediatric Surgeons Congenital Anomalies Surveillance, S. Hirschsprung\u2019s disease in the UK and Ireland: Incidence and anomalies","volume":"102","author":"Bradnock","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00383-017-4110-7","article-title":"Hirschsprung\u2019s disease in twins: A systematic review and meta-analysis","volume":"33","author":"Henderson","year":"2017","journal-title":"Pediatr. Surg. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.3748\/wjg.v21.i33.9683","article-title":"Pediatr. intestinal motility disorders","volume":"21","author":"Gfroerer","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jpedsurg.2016.11.023","article-title":"Functional outcomes in Hirschsprung disease: A single institution\u2019s 12-year experience","volume":"52","author":"Thakkar","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s00384-019-03399-8","article-title":"Redo surgery with longitudinal resection for dilated bowel in Hirschsprung disease: An illustrative case series","volume":"34","author":"Roorda","year":"2019","journal-title":"Int. J. Color. Dis."},{"key":"ref_8","first-page":"277","article-title":"Short Term and Long term Outcome of Single-Stage Trans-anal Pull Through for Hirschsprung\u2019s Disease in Neonates and Infants","volume":"9","year":"2020","journal-title":"J. Neonatal. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1053\/j.sempedsurg.2012.07.008","article-title":"Long-term outcomes of Hirschsprung\u2019s disease","volume":"21","author":"Rintala","year":"2012","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1148\/rg.2019190086","article-title":"Neurocristopathies: Enigmatic Appearances of Neural Crest Cell-derived Abnormalities","volume":"39","author":"Sato","year":"2019","journal-title":"RadioGraphics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.gde.2012.06.001","article-title":"The neural crest in vertebrate evolution","volume":"22","author":"Dupin","year":"2012","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/ajmg.a.33702","article-title":"Cranial neural crest cells on the move: Their roles in craniofacial development","volume":"155","author":"Cordero","year":"2011","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1387\/ijdb.160408gv","article-title":"Trunk neural crest cells: Formation, migration and beyond","volume":"61","author":"Cerrizuela","year":"2017","journal-title":"Int. J. Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1002\/dvdy.22715","article-title":"Vagal neural crest cell migratory behavior: A transition between the cranial and trunk crest","volume":"240","author":"Kuo","year":"2011","journal-title":"Dev. Dyn."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1053\/j.gastro.2011.06.002","article-title":"Analysis of the Sacral Neural Crest Cell Contribution to the Hindgut Enteric Nervous System in the Mouse Embryo","volume":"141","author":"Wang","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1242\/dev.01197","article-title":"Cardiac neural crest of the mouse embryo: Axial level of origin, migratory pathway and cell autonomy of the splotch(Sp2H) mutant effect","volume":"131","author":"Chan","year":"2004","journal-title":"Development"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ydbio.2011.12.042","article-title":"Development and evolution of the neural crest: An overview","volume":"366","author":"LeDouarin","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1242\/dev.091751","article-title":"The neural crest","volume":"140","author":"Mayor","year":"2013","journal-title":"Development"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4103\/0973-029X.164536","article-title":"Neural crest: The fourth germ layer","volume":"19","author":"Shyamala","year":"2015","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1525-142x.2000.00032.x","article-title":"The neural crest as a fourth germ layer and vertebrates as quadroblastic not triploblastic","volume":"2","author":"Hall","year":"2001","journal-title":"Evol. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1469-7580.2007.00773.x","article-title":"The development of the neural crest in the human","volume":"211","year":"2007","journal-title":"J. Anat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0046-8177(74)80021-3","article-title":"The neurocristopathiesA unifying concept of disease arising in neural crest maldevelopment","volume":"5","author":"Bolande","year":"1974","journal-title":"Hum. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/bdrc.21081","article-title":"The neural crest: A versatile organ system","volume":"102","author":"Zhang","year":"2014","journal-title":"Birth Defects Res. Part C Embryo Today Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/s41583-018-0041-0","article-title":"Enteric nervous system development: What could possibly go wrong?","volume":"19","author":"Rao","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_25","first-page":"13234","article-title":"Faculty Opinions recommendation of the first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems","volume":"30","author":"Jb","year":"2018","journal-title":"Fac. Opin. Post-Publ. Peer Rev. Biomed. Lit."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/cne.901010212","article-title":"The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo","volume":"101","author":"Yntema","year":"1954","journal-title":"J. Comp. Neurol."},{"key":"ref_27","first-page":"31","article-title":"The migration of neural crest cells to the wall of the digestive tract in avian embryo","volume":"30","author":"Teillet","year":"1973","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_28","first-page":"16","article-title":"Enteric nervous system development: Analysis of the selective developmental potentialities of vagal and sacral neural crest cells using quail-chick chimeras","volume":"262","author":"Burns","year":"2001","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/dvdy.20974","article-title":"Behavior of enteric neural crest-derived cells varies with respect to the migratory wavefront","volume":"236","author":"Druckenbrod","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Simkin, J.E., Zhang, D., Rollo, B.N., and Newgreen, D.F. (2013). Retinoic Acid Upregulates Ret and Induces Chain Migration and Population Expansion in Vagal Neural Crest Cells to Colonise the Embryonic Gut. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064077"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ajmg.a.37663","article-title":"Frederik Ruysch (1638\u20131731): Historical perspective and contemporary analysis of his teratological legacy","volume":"173","author":"Boer","year":"2016","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jpedsurg.2015.10.021","article-title":"Hirschsprung\u2019s disease: A bridge for science and surgery","volume":"51","author":"Tam","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jpedsurg.2006.09.024","article-title":"Historic milestones of Hirschsprung\u2019s disease (commemorating the 90th anniversary of Professor Harald Hirschsprung\u2019s death)","volume":"42","author":"Skaba","year":"2007","journal-title":"J. Pediatr. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.5409\/wjcp.v4.i4.120","article-title":"Hirschsprung\u2019s disease: Historical notes and pathological diagnosis on the occasion of the 100(th) anniversary of Dr. Harald Hirschsprung\u2019s death","volume":"4","author":"Sergi","year":"2015","journal-title":"World. J. Clin. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1053\/j.scrs.2006.02.003","article-title":"The History of Hirschsprung\u2019s Disease: Then and Now","volume":"17","author":"Masiakos","year":"2006","journal-title":"Semin. Colon Rectal Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1056\/NEJMe1902827","article-title":"Complex Simplicity and Hirschsprung\u2019s Disease","volume":"380","author":"Goldstein","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"552","DOI":"10.5056\/jnm15079","article-title":"Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model","volume":"21","author":"Stamp","year":"2015","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1055\/s-0039-1694745","article-title":"Animal Models of Hirschsprung\u2019s Disease: State of the Art in Translating Experimental Research to the Bedside. Eur","volume":"29","author":"Fujiwara","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/00001574-200201000-00013","article-title":"The pathogenesis of Hirschsprung disease","volume":"18","author":"Belknap","year":"2002","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2013.03.001","article-title":"The developmental etiology and pathogenesis of Hirschsprung disease","volume":"162","author":"Tjaden","year":"2013","journal-title":"Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0896-6273(00)81064-8","article-title":"GFRalpha-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival","volume":"25","author":"Tansey","year":"2000","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1242\/dev.129.22.5151","article-title":"Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis","volume":"129","author":"Natarajan","year":"2002","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.mod.2004.12.008","article-title":"Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent","volume":"122","author":"Elworthy","year":"2005","journal-title":"Mech. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1242\/dev.040550","article-title":"Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation","volume":"137","author":"Fu","year":"2010","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ydbio.2017.10.021","article-title":"Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells","volume":"433","author":"Uribe","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_46","first-page":"640","article-title":"An embryological point of view on associated congenital anomalies of children with Hirschsprung disease","volume":"116","author":"Slavikova","year":"2015","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.2007.053959","article-title":"Hirschsprung disease, associated syndromes and genetics: A review","volume":"45","author":"Amiel","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s00383-012-3175-6","article-title":"Chromosomal and related Mendelian Syndromes associated with Hirschsprung\u2019s disease","volume":"28","author":"Moore","year":"2012","journal-title":"Pediatr. Surg. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00383-006-1655-2","article-title":"The contribution of associated congenital anomalies in understanding Hirschsprung\u2019s disease","volume":"22","author":"Moore","year":"2006","journal-title":"Pediatr. Surg. Int."},{"key":"ref_50","unstructured":"Kushch, N.L., Grona, V.N., Kimbarovskaia, E.M., and Evseeva, L.I. (1988). Clinico-immunologic comparisons of developmental defects of the large intestine in children. Klin. Khirurgiia, 10\u201312."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1093\/intimm\/dxm060","article-title":"Mesenchymal cells are required for functional development of thymic epithelial cells","volume":"19","author":"Itoi","year":"2007","journal-title":"Int. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.4049\/jimmunol.180.5.3183","article-title":"Contribution of Neural Crest-Derived Cells in the Embryonic and Adult Thymus","volume":"180","author":"Foster","year":"2008","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1210\/en.2004-0274","article-title":"A Moderate and Transient Deficiency of Maternal Thyroid Function at the Beginning of Fetal Neocorticogenesis Alters Neuronal Migration","volume":"145","author":"Cuevas","year":"2004","journal-title":"Endocrinology"},{"key":"ref_54","first-page":"89","article-title":"Differential diagnosis of Hirschsprung\u2019s disease and congenital hypothyroidism in children","volume":"134","author":"Mustafin","year":"1985","journal-title":"Vestn. Khir. Im. II Grek."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.earlhumdev.2011.07.009","article-title":"Higher incidence of thyroid agenesis in Mexican newborns with congenital hypothyroidism associated with birth defects","volume":"88","year":"2012","journal-title":"Early Hum. Dev."},{"key":"ref_56","first-page":"94","article-title":"A case of Hirschsprung disease: Does thyroid hormone have any effect?","volume":"51","author":"Eren","year":"2009","journal-title":"Turk. J. Pediatr."},{"key":"ref_57","first-page":"245","article-title":"Hirschsprungs disease with congenital hypothyroidism","volume":"49","author":"Kota","year":"2012","journal-title":"Indian Pediatr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1177\/1066896916675729","article-title":"Spectrum of Clinicopathological Deviations in Long-Segment Hirschsprung Disease Compared With Short-Segment Hirschsprung Disease: A Single-Institution Study","volume":"25","author":"Alnajar","year":"2016","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_59","first-page":"837","article-title":"The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands","volume":"29","author":"Varga","year":"2008","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s00383-013-3364-y","article-title":"Interstitial cells of Cajal in the normal human gut and in Hirschsprung disease","volume":"29","author":"Gfroerer","year":"2013","journal-title":"Pediatr. Surg. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1319-3767.105909","article-title":"The importance of interstitial cells of cajal in the gastrointestinal tract","volume":"19","year":"2013","journal-title":"Saudi J. Gastroenterol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/jcmm.13375","article-title":"Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells","volume":"22","author":"Radenkovic","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0016-5085(96)70057-4","article-title":"Interstitial cells of Cajal in human colon and in Hirschsprung\u2019s disease","volume":"111","author":"Vanderwinden","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"928","DOI":"10.5858\/2002-126-0928-ADOICO","article-title":"Altered distribution of interstitial cells of Cajal in Hirschsprung disease","volume":"126","author":"Rolle","year":"2002","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1007\/s00383-003-1026-1","article-title":"Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung\u2019s disease","volume":"19","author":"Newman","year":"2003","journal-title":"Pediatr. Surg. Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.jpedsurg.2017.01.065","article-title":"Cotransplantation of neuroepithelial stem cells with interstitial cells of Cajal improves neuronal differentiation in a rat aganglionic model","volume":"52","author":"Zhang","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_67","first-page":"338","article-title":"The role of mast cells in pediatric gastrointestinal disease","volume":"32","author":"Ravanbakhsh","year":"2019","journal-title":"Ann. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1600-065X.2007.00523.x","article-title":"Human mast cells, bacteria, and intestinal immunity","volume":"217","author":"Bischoff","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0022-3468(99)90069-6","article-title":"Mast cells and gut nerve development: Implications for hirschsprung\u2019s disease and intestinal neuronal dysplasia","volume":"34","author":"Kobayashi","year":"1999","journal-title":"J. Pediatr. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s003830000467","article-title":"Mast-cells distribution and colonic mucin composition in Hirschsprung\u2019s disease and intestinal neuronal dysplasia","volume":"17","author":"Demirbilek","year":"2001","journal-title":"Pediatr. Surg. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2478\/v10042-008-0008-5","article-title":"Topography and morphometry of intestinal mast cells in children with Hirschsprung\u2019s disease","volume":"46","author":"Hermanowicz","year":"2008","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1007\/s12098-017-2371-8","article-title":"Hirschsprung Disease\u2014Current Diagnosis and Management","volume":"84","author":"Das","year":"2017","journal-title":"Indian J. Pediatr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00383-016-4038-3","article-title":"Advances in understanding functional variations in the Hirschsprung disease spectrum (variant Hirschsprung disease)","volume":"33","author":"Moore","year":"2016","journal-title":"Pediatr. Surg. Int."},{"key":"ref_74","first-page":"264","article-title":"Diagnosis of Hirschsprung\u2019s disease with particular emphasis on histopathology. A systematic review of current literature","volume":"9","author":"Szylberg","year":"2014","journal-title":"Prz. Gastroenterol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00383-013-3351-3","article-title":"Classification and diagnostic criteria of variants of Hirschsprung\u2019s disease","volume":"29","author":"Friedmacher","year":"2013","journal-title":"Pediatr. Surg. Int."},{"key":"ref_76","first-page":"1279","article-title":"Intestinal Dysganglionosis and Other Disorders of Intestinal Motility","volume":"Volume 102","author":"Coran","year":"2012","journal-title":"Pediatr. Surgery"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2169\/internalmedicine.47.0275","article-title":"Megacolon in an adult case of hypoganglionosis, a pseudo-Hirschsprung\u2019s disease: An autopsy study","volume":"47","author":"Ito","year":"2008","journal-title":"Intern. Med."},{"key":"ref_78","first-page":"1171","article-title":"Human newborn and adult myenteric plexus grows in different patterns","volume":"43","author":"Mestres","year":"1997","journal-title":"Cell. Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.autneu.2004.05.007","article-title":"Age-related changes in the morphology of the myenteric plexus of the human colon","volume":"113","author":"Hanani","year":"2004","journal-title":"Auton. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jcmgh.2015.09.007","article-title":"Enteric Neural Cells From Hirschsprung Disease Patients Form Ganglia in Autologous Aneuronal Colon","volume":"2","author":"Rollo","year":"2016","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.stemcr.2017.07.017","article-title":"Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine","volume":"9","author":"Schlieve","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nm.4233","article-title":"Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system","volume":"23","author":"Workman","year":"2017","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10561-014-9462-9","article-title":"Induced pluripotent stem cells and their implication for regenerative medicine","volume":"16","author":"Csobonyeiova","year":"2014","journal-title":"Cell Tissue Bank."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-019-0718-x","article-title":"\u201cToo much guts and not enough brains\u201d: (epi)Genetic mechanisms and future therapies of Hirschsprung disease\u2014A review","volume":"11","author":"Jaroy","year":"2019","journal-title":"Clin. Epigenetics"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/11\/611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:33:09Z","timestamp":1760178789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/11\/611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,13]]},"references-count":84,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["medicina56110611"],"URL":"https:\/\/doi.org\/10.3390\/medicina56110611","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,13]]}}}