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Its genetic and phenotypic variability and management options remain poorly characterized. This study correlates genotype with phenotype and subsequently analyzes treatment and outcome of patients with pediatric-onset MMIHS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 26 MMIHS patients (median age 97 months, 62% female) with molecular diagnostics in 19 patients at a German quaternary intestinal rehabilitation center followed between 2012 and 2025.\n                      <jats:italic>ACTG2<\/jats:italic>\n                      (15\/19) was the most common causative gene variant, followed by\n                      <jats:italic>MYH11<\/jats:italic>\n                      (2\/19),\n                      <jats:italic>MYLK<\/jats:italic>\n                      (1\/19), and\n                      <jats:italic>LMOD1<\/jats:italic>\n                      (1\/19). Megacystis was present in 96% (all detected prenatally), intestinal hypoperistalsis in 100%, and microcolon in 57%. High rates of proximal intestinal stenosis (35%), mal-\/non-rotation (39%), IFALD (58%), and Cholelithiasis (65%) were observed. All patients experienced clinical (sub)ileus, with 85% requiring ostomy and parenteral nutrition, key determinants of unfavorable outcome. Notably,\n                      <jats:italic>ACTG2<\/jats:italic>\n                      variants at P39 or R40 were significantly associated with more favorable outcome, evading these measures, in contrast to variants at R63, R178 or R257 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01). Overall long-term survival in our cohort was 88%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this second-largest pediatric MMIHS cohort worldwide, genotype correlated with severity and outcomes, with\n                      <jats:italic>ACTG2<\/jats:italic>\n                      P39\/R40 variants linked to better prognosis. Frequent occurrences of proximal intestinal stenosis, mal\/non-rotations, and cholelithiasis were identified, findings that have thus far been underestimated in clinical assessments. Prenatal megacystis enables presumptive diagnosis for MMIHS, which should prompt early molecular diagnostics and genotype-guided management. Individualized care at a multidisciplinary intestinal rehabilitation center resulted in 88% long-term survival.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04154-9","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:05:55Z","timestamp":1765526755000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genotype-phenotype correlation and management of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome: a descriptive cohort study"],"prefix":"10.1186","volume":"21","author":[{"given":"Johannes","family":"Hilberath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Tsiflikas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Lieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Luithle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Sturm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Warmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-5906","authenticated-orcid":false,"given":"Christoph","family":"Slavetinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"4154_CR1","doi-asserted-by":"publisher","first-page":"e81","DOI":"10.1097\/MPG.0000000000003008","volume":"72","author":"KM Prathapan","year":"2021","unstructured":"Prathapan KM, King DE, Raghu VK, Ackerman K, Presel T, Yaworski JA, et al. 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As decided by the ethics committee, informed consent including consent for publication was obtained from patients\/caregivers who could be approached with reasonable effort.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors reviewed the final version of the manuscript and provided written agreement for its publication in\n                      Orphanet Journal of Rare Diseases\n                      .","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no financial and\/or non-financial competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}