{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:54:21Z","timestamp":1791258861401,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Microvillus inclusion disease (MVID) is a rare congenital enteropathy caused by defects in intestinal epithelial apical trafficking and polarity. Although its genetic basis is well established, the clinical spectrum and genotype\u2013phenotype correlations remain incompletely defined. We aimed to systematically characterize the clinical and genetic features of MVID and investigate genotype\u2013phenotype correlations. A systematic review of MVID literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses (PRISMA) statement, with database searches performed from inception to August 5, 2026. A total of 118 studies comprising 336 patients were included. Intractable diarrhea was reported in 98.8% (332\/336). Extraintestinal involvement was documented in 243 patients and was most often hepatic (127\/243, 52.3%), with cholestasis in 80\/127 (63.0%), cirrhosis in 16\/127 (12.6%), and hepatic failure in 8\/127 (6.3%). Among 287 patients with treatment data, 280 (97.6%) received total parenteral nutrition (TPN). Management patterns changed across reporting eras, with intestinal transplantation reported in 33.3% (23\/69) of patients in 1996\u20132010 and 12.9% (16\/124) in 2011\u20132026. Pathogenic variants were identified most commonly in\n                    <jats:italic>MYO5B<\/jats:italic>\n                    , followed by\n                    <jats:italic>STXBP2<\/jats:italic>\n                    ,\n                    <jats:italic>STX3<\/jats:italic>\n                    , and\n                    <jats:italic>UNC45A<\/jats:italic>\n                    . Bi\u2010allelic null\n                    <jats:italic>MYO5B<\/jats:italic>\n                    variants were associated with earlier onset than bi\u2010allelic non\u2010null variants (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001); in severe hepatic involvement, the presence of at least one null\n                    <jats:italic>MYO5B<\/jats:italic>\n                    variant was associated with reduced liver\u2010intestine transplant\u2010free survival (log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.040). MVID is characterized by intractable diarrhea and substantial hepatic involvement. Molecular diagnosis clarifies the genetic etiology and provides a basis for genotype\u2010informed clinical stratification. Treatment strategies should be interpreted in an era\u2010specific context.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Systematic Review Registration:<\/jats:bold>\n                    PROSPERO (CRD42024503464).\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70314","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:47:31Z","timestamp":1791258451000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Spectrum, Genetic Profile, and Genotype\u2013Phenotype Correlations in Microvillus Inclusion Disease: A Systematic Review"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9295-6569","authenticated-orcid":false,"given":"Xiang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Jun","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Zong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3390\/jcm10030481","article-title":"Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated With MYO5B Mutations","volume":"10","author":"Aldrian D.","year":"2021","journal-title":"Journal of Clinical Medicine"},{"issue":"2","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.1097\/PG9.0000000000000309","article-title":"Microvillus Inclusion Disease Caused by MYO5B: Different Presentation and Phenotypes Despite Same Mutation","volume":"4","author":"Andreassen B. U.","year":"2023","journal-title":"JPGN Reports"},{"issue":"12","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1172\/JCI40732","article-title":"Munc18\u20102 Deficiency Causes Familial Hemophagocytic Lymphohistiocytosis Type 5 and Impairs Cytotoxic Granule Exocytosis in Patient NK Cells","volume":"119","author":"C\u00f4te M.","year":"2009","journal-title":"Journal of Clinical Investigation"},{"issue":"5","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/0016-5085(78)90458-4","article-title":"Familial Enteropathy: A Syndrome of Protracted Diarrhea From Birth, Failure to Thrive, and Hypoplastic Villus Atrophy","volume":"75","author":"Davidson G. P.","year":"1978","journal-title":"Gastroenterology"},{"issue":"10","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI154997","article-title":"UNC45A Deficiency Causes Microvillus Inclusion Disease\u2010Like Phenotype by Impairing Myosin VB\u2010Dependent Apical Trafficking","volume":"132","author":"Duclaux\u2010Loras R.","year":"2022","journal-title":"Journal of Clinical Investigation"},{"issue":"6","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1053\/j.gastro.2018.08.025","article-title":"Loss of MYO5B Leads to Reductions in Na+ Absorption With Maintenance of CFTR\u2010Dependent cl\u2010 Secretion in Enterocytes","volume":"155","author":"Engevik A. C.","year":"2018","journal-title":"Gastroenterology"},{"issue":"24","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1002\/ajmg.a.32605","article-title":"Navajo Microvillous Inclusion Disease Is due to a Mutation in MYO5B","volume":"146","author":"Erickson R. P.","year":"2008","journal-title":"American Journal of Medical Genetics. Part A"},{"issue":"3","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ajhg.2018.01.009","article-title":"Loss\u2010Of\u2010Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility","volume":"102","author":"Esteve C.","year":"2018","journal-title":"American Journal of Human Genetics"},{"issue":"1","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/hep.26974","article-title":"MYO5B and Bile Salt Export Pump Contribute to Cholestatic Liver Disorder in Microvillous Inclusion Disease","volume":"60","author":"Girard M.","year":"2014","journal-title":"Hepatology"},{"issue":"8","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s00439-021-02284-1","article-title":"Pathogenic STX3 Variants Affecting the Retinal and Intestinal Transcripts Cause an Early\u2010Onset Severe Retinal Dystrophy in Microvillus Inclusion Disease Subjects","volume":"140","author":"Janecke A. R.","year":"2021","journal-title":"Human Genetics"},{"issue":"20","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI169234","article-title":"Patient\u2010Derived Enteroids Provide a Platform for the Development of Therapeutic Approaches in Microvillus Inclusion Disease","volume":"133","author":"Kalashyan M.","year":"2023","journal-title":"Journal of Clinical Investigation"},{"issue":"5","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1097\/TP.0000000000003065","article-title":"New Insights Into the Indications for Intestinal Transplantation: Consensus in the Year 2019","volume":"104","author":"Kaufman S. S.","year":"2020","journal-title":"Transplantation"},{"issue":"1","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"G142","DOI":"10.1152\/ajpgi.00041.2016","article-title":"Identification of Intestinal Ion Transport Defects in Microvillus Inclusion Disease","volume":"311","author":"Kravtsov D. V.","year":"2016","journal-title":"American Journal of Physiology. Gastrointestinal and Liver Physiology"},{"issue":"1","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10010022","article-title":"Pharmacological and Parenteral Nutrition\u2010Based Interventions in Microvillus Inclusion Disease","volume":"10","author":"Leng C.","year":"2020","journal-title":"Journal of Clinical Medicine"},{"issue":"17","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10173935","article-title":"Risk and Clinical Significance of Idiopathic Preterm Birth in Microvillus Inclusion Disease","volume":"10","author":"Leng C.","year":"2021","journal-title":"Journal of Clinical Medicine"},{"issue":"10","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/ng.225","article-title":"MYO5B Mutations Cause Microvillus Inclusion Disease and Disrupt Epithelial Cell Polarity","volume":"40","author":"M\u00fcller T.","year":"2008","journal-title":"Nature Genetics"},{"issue":"1","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/hep.31002","article-title":"A Molecular Mechanism Underlying Genotype\u2010Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations","volume":"72","author":"Overeem A. W.","year":"2020","journal-title":"Hepatology"},{"issue":"4","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/j.1536-4801.1992.tb10569.x","article-title":"Familial Microvillous Atrophy: A Clinicopathological Survey of 23 Cases","volume":"14","author":"Phillips A. D.","year":"1992","journal-title":"Journal of Pediatric Gastroenterology and Nutrition"},{"issue":"10","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.clnu.2023.07.019","article-title":"ESPEN Guideline on Chronic Intestinal Failure in Adults \u2010 Update 2023","volume":"42","author":"Pironi L.","year":"2023","journal-title":"Clinical Nutrition"},{"issue":"5","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1002\/hep.29020","article-title":"Defects in Myosin VB Are Associated With a Spectrum of Previously Undiagnosed Low \u03b3\u2010Glutamyltransferase Cholestasis","volume":"65","author":"Qiu Y. L.","year":"2017","journal-title":"Hepatology"},{"issue":"3","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","DOI":"10.1111\/petr.14756","article-title":"From Intestinal Failure to Transplantation: Review on the Current Need for Transplant Indications Under Multidisciplinary Transplant Programs Worldwide","volume":"28","author":"Raghu V. K.","year":"2024","journal-title":"Pediatric Transplantation"},{"issue":"5","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/humu.21224","article-title":"Loss\u2010Of\u2010Function of MYO5B Is the Main Cause of Microvillus Inclusion Disease: 15 Novel Mutations and a CaCo\u20102 RNAi Cell Model","volume":"31","author":"Ruemmele F. M.","year":"2010","journal-title":"Human Mutation"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2025.151669","article-title":"A Liver\u2010Specific Mouse Model for MYO5B\u2010Associated Cholestasis Reveals a Toxic Gain\u2010Of\u2010Function as Underlying Disease Mechanism","volume":"758","author":"She H. Y.","year":"2025","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"6","key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.jcmgh.2024.01.015","article-title":"Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease","volume":"17","author":"Sun M.","year":"2024","journal-title":"Cellular and Molecular Gastroenterology and Hepatology"},{"issue":"15","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11154331","article-title":"Fetal Bowel Abnormalities Suspected by Ultrasonography in Microvillus Inclusion Disease: Prevalence and Clinical Significance","volume":"11","author":"Sun Y.","year":"2022","journal-title":"Journal of Clinical Medicine"},{"issue":"4","key":"e_1_2_11_27_1","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/hep.31430","article-title":"Unequal Effects of Myosin 5B Mutations in Liver and Intestine Determine the Clinical Presentation of Low\u2010Gamma\u2010Glutamyltransferase Cholestasis","volume":"72","author":"IJzendoorn S. C. D.","year":"2020","journal-title":"Hepatology"},{"issue":"3","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1083\/jcb.201506112","article-title":"Cargo\u2010Selective Apical Exocytosis in Epithelial Cells Is Conducted by Myo5B, Slp4a, Vamp7, and Syntaxin 3","volume":"211","author":"Vogel G. F.","year":"2015","journal-title":"Journal of Cell Biology"},{"issue":"14","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.94564","article-title":"Disrupted Apical Exocytosis of Cargo Vesicles Causes Enteropathy in FHL5 Patients With Munc18\u20102 Mutations","volume":"2","author":"Vogel G. F.","year":"2017","journal-title":"JCI Insight"},{"issue":"2","key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/liv.15104","article-title":"MYO5B\u2010Associated Diseases: Novel Liver\u2010Related Variants and Genotype\u2010Phenotype Correlation","volume":"42","author":"Wang L.","year":"2022","journal-title":"Liver International"},{"issue":"9","key":"e_1_2_11_31_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jcmgh.2026.101805","article-title":"A Molecular Mechanism of Intrahepatic Cholestasis in Osteo\u2010Oto\u2010Hepato\u2010Enteric Syndrome","volume":"20","author":"Zhou Z.","year":"2026","journal-title":"Cellular and Molecular Gastroenterology and Hepatology"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70314","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:47:35Z","timestamp":1791258455000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":30,"alternative-id":["10.1002\/ajmg.a.70314"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70314","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"assertion":[{"value":"2026-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70314"}}