{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:59:20Z","timestamp":1790179160425,"version":"4.1.0"},"reference-count":191,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Human beings are characterized by a left\u2013right asymmetric arrangement of their internal organs, and the heart is the first organ to break symmetry in the developing embryo. Aberrations in normal left\u2013right axis determination during embryogenesis lead to a wide spectrum of abnormal internal laterality phenotypes, including situs inversus and heterotaxy. In more than 90% of instances, the latter condition is accompanied by complex and severe cardiovascular malformations. Atrioventricular canal defect and transposition of the great arteries\u2014which are particularly frequent in the setting of heterotaxy\u2014are commonly found in situs solitus with or without genetic syndromes. Here, we review current data on morphogenesis of the heart in human beings and animal models, familial recurrence, and upstream genetic pathways of left\u2013right determination in order to highlight how some isolated congenital heart diseases, very common in heterotaxy, even in the setting of situs solitus, may actually be considered in the pathogenetic field of laterality defects.<\/jats:p>","DOI":"10.3390\/jcdd5020024","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T03:20:27Z","timestamp":1525317627000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Some Isolated Cardiac Malformations Can Be Related to Laterality Defects"],"prefix":"10.3390","volume":"5","author":[{"given":"Paolo","family":"Versacci","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaminia","family":"Pugnaloni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital and Research Institute, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Putotto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Unolt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-0829","authenticated-orcid":false,"given":"Giulio","family":"Calcagni","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiac Surgery, Bambino Ges\u00f9 Children\u2019s Hospital and Research Institute, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4934","authenticated-orcid":false,"given":"Anwar","family":"Baban","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Cardiac Surgery, Bambino Ges\u00f9 Children\u2019s Hospital and Research Institute, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(00)81705-5","article-title":"Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein","volume":"95","author":"Nonaka","year":"1998","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.tig.2017.06.004","article-title":"Left\u2013Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis","volume":"33","author":"Grimes","year":"2017","journal-title":"Trends Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0070-2153(08)00806-5","article-title":"Chapter Six Cilia. 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