{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:35:14Z","timestamp":1776926114467,"version":"3.51.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Shone syndrome is a rare congenital heart disease characterized by multilevel left-sided obstructive lesions. KMT2D variants cause Kabuki syndrome and are frequently associated with left-sided obstructive congenital heart defects, but their contribution to Shone syndrome remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report a 4-year-old girl with a Shone syndrome phenotype. Trio whole-exome sequencing (WES) was performed in the proband and her parents, with Sanger sequencing for confirmation and segregation analysis. Echocardiography and CT angiography were used to delineate cardiac anatomy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Imaging and intraoperative findings demonstrated a supramitral ring with mitral stenosis, abnormal subvalvular apparatus, an interrupted\/hypoplastic aortic arch with extensive collateral circulation, and a bicuspid aortic valve. Trio-WES identified a heterozygous KMT2D variant (NM_003482.4:c.15565G\u2009&amp;gt;\u2009A, p.Gly5189Arg) in the proband, which was also present in her clinically unaffected mother and younger sister, indicating maternal inheritance with variable expressivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This report describes a child with multilevel left-sided obstruction and an inherited KMT2D variant, together with limited Kabuki-like facial features that did not meet the 2019 international consensus clinical criteria for Kabuki syndrome. While the observation raises the possibility that KMT2D-related pathways may contribute to Shone complex, a causal relationship cannot be inferred from a single family and requires additional genetic and functional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1651823","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:35:59Z","timestamp":1776922559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Exploring KMT2D mutation in Shone syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Peiwen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corlina","family":"Matthew","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guozhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"An","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/0002-9149(63)90098-5","article-title":"The developmental complex of \u201cparachute mitral valve,\u201d supravalvular ring of left atrium, subaortic stenosis, and coarctation of aorta","volume":"11","author":"Shone","year":"1963","journal-title":"Am J Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.case.2024.01.002","article-title":"Echocardiography to the rescue in adult-onset partial Shone complex","volume":"8","author":"Saldana","year":"2024","journal-title":"CASE"},{"key":"B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-42937-9_58-1","article-title":"Shone\u2019s complex","volume-title":"Pediatric Cardiology: Fetal, Pediatric, and Adult Congenital Heart Diseases","author":"Wang","year":"2023"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1002\/ajmg.a.38417","article-title":"Congenital heart defects in molecularly proven kabuki syndrome patients","volume":"173","author":"Digilio","year":"2017","journal-title":"Am J Med Genet A"},{"key":"B5","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3345\/kjp.2015.58.7.256","article-title":"The strong association of left-side heart anomalies with kabuki syndrome","volume":"58","author":"Yoon","year":"2015","journal-title":"Korean J Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World medical association declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"J Am Med Assoc"},{"key":"B7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the ACMG and the AMP","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1136\/jmedgenet-2018-105625","article-title":"Kabuki syndrome: international consensus diagnostic criteria","volume":"56","author":"Adam","year":"2019","journal-title":"J Med Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/s0002-9149(99)80357-9","article-title":"Echocardiographic evaluation of congenital mitral valve anomalies in children","volume":"76","author":"Banerjee","year":"1995","journal-title":"Am J Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1177\/10892532231223840","article-title":"Perioperative and anesthetic considerations in Shone\u2019s complex","volume":"28","author":"Landsem","year":"2024","journal-title":"Semin Cardiothorac Vasc Anesth"},{"key":"B11","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.cjca.2016.09.005","article-title":"Shone complex: an under-recognized congenital heart disease with substantial morbidity in adulthood","volume":"33","author":"Aslam","year":"2017","journal-title":"Can J Cardiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1177\/10892532231203372","article-title":"Surgical considerations in Shone complex","volume":"27","author":"Yang","year":"2023","journal-title":"Semin Cardiothorac Vasc Anesth"},{"key":"B13","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1002\/humu.23026","article-title":"Mutation update for kabuki syndrome genes KMT2D and KDM6A and further delineation of X-linked kabuki syndrome subtype 2","volume":"37","author":"B\u00f6gershausen","year":"2016","journal-title":"Hum Mutat"},{"key":"B14","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00439-011-1004-y","article-title":"A mutation screen in patients with Kabuki syndrome","volume":"130","author":"Li","year":"2011","journal-title":"Hum Genet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/s41436-019-0743-3","article-title":"A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome","volume":"22","author":"Cuvertino","year":"2020","journal-title":"Genet Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"4443","DOI":"10.1093\/hmg\/ddv180","article-title":"Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development","volume":"24","author":"Van Laarhoven","year":"2015","journal-title":"Hum Mol Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e12568","DOI":"10.1111\/gbb.12568","article-title":"Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki syndrome","volume":"18","author":"Yamamoto","year":"2019","journal-title":"Genes Brain Behav"},{"key":"B18","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1242\/dev.132688","article-title":"KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation","volume":"143","author":"Ang","year":"2016","journal-title":"Development"},{"key":"B19","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/genes12040468","article-title":"Kabuki syndrome-clinical review with molecular aspects","volume":"12","author":"Boniel","year":"2021","journal-title":"Genes"},{"key":"B20","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.seizure.2011.06.005","article-title":"Long-term outcome of epilepsy in Kabuki syndrome","volume":"20","author":"Verrotti","year":"2011","journal-title":"Seizure"},{"key":"B21","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.braindev.2017.03.025","article-title":"Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations","volume":"39","author":"Kurahashi","year":"2017","journal-title":"Brain Dev"},{"key":"B22","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.braindev.2009.12.006","article-title":"Seizures and EEG pattern in Kabuki syndrome","volume":"32","author":"Lodi","year":"2010","journal-title":"Brain Dev"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1651823\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:36:05Z","timestamp":1776922565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1651823\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":22,"alternative-id":["10.3389\/fcvm.2026.1651823"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1651823","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"article-number":"1651823"}}