{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T20:40:02Z","timestamp":1777149602467,"version":"3.51.4"},"posted":{"date-parts":[[2025,12,29]]},"group-title":"Genetic and Genomic Medicine","reference-count":27,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Nonsyndromic cleft lip with or without cleft palate (NSCL\/P) presents in diverse phenotypic forms defined by laterality, symmetry, and completeness. This study examined these features and their associations with sex, race, and ethnicity in a multiethnic cohort of 3,561 individuals from North America, South America, Asia, and Africa.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Associations were evaluated using Chi-square or Fisher\u2019s exact tests with Bonferroni correction.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Left unilateral clefts were the most prevalent, followed by right unilateral and bilateral clefts. The most common phenotype was a left complete unilateral cleft lip; the rarest was an asymmetric bilateral cleft with complete right-sided involvement. Among asymmetric bilateral cases, left-sided completeness was significantly more frequent than right-sided (p &lt; 0.001), indicating the left side is both more commonly and more severely affected. Bilateral clefts \u2014 both symmetric and asymmetric \u2014 were more prevalent in males, while unilateral clefts were more common in females (p &lt; 0.001). Asymmetric bilateral clefts occurred most frequently in Whites, whereas symmetric bilateral clefts were most common among Asians and Hispanics. Despite sex differences in bilateral cleft prevalence, completeness did not vary by sex for bilateral cases. For unilateral clefts, females showed higher completeness rates than males, and Asians and Hispanics\/Latinos were more likely to exhibit complete unilateral clefts. Left unilateral clefts were most prevalent among Asians.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Sex, race, and ethnicity influence cleft laterality and symmetry, but cleft completeness appears sex-independent. The dissociation between side predominance and completeness suggests that distinct biological mechanisms govern cleft initiation and severity.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.29.25343144","type":"posted-content","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T01:55:11Z","timestamp":1767059711000},"source":"Crossref","is-referenced-by-count":0,"title":["Laterality, Symmetry and Completeness Patterns of Nonsyndromic Orofacial Clefts in a Multiethnic Cohort"],"prefix":"10.64898","author":[{"given":"Christina E.","family":"Spencer","sequence":"first","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-1866","authenticated-orcid":false,"given":"Ligiane A","family":"Machado-Paula","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Qian","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-5964","authenticated-orcid":false,"given":"Azeez","family":"Butali","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen J.","family":"Buxo-Martinez","sequence":"additional","affiliation":[{"name":"University of Puerto Rico, School of Dental Medicine, Dental and Craniofacial Genomics Core"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-1871","authenticated-orcid":false,"given":"Carmencita D.","family":"Padilla","sequence":"additional","affiliation":[{"name":"University of the Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Restrepo-Muneton","sequence":"additional","affiliation":[{"name":"Clinica Noel, Medell\u00edn, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Consuelo","family":"Valencia-Ramirez","sequence":"additional","affiliation":[{"name":"Clinica Noel, Medell\u00edn, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross E.","family":"Long","sequence":"additional","affiliation":[{"name":"Lancaster, PA, Cleft Palate Clinic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-4556","authenticated-orcid":false,"given":"Seth M.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"University of North Carolina, Adams School of Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-2832","authenticated-orcid":false,"given":"Mary L.","family":"Marazita","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine; and Department of Human Genetics, School of Public Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-6551","authenticated-orcid":false,"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-4818","authenticated-orcid":false,"given":"Lina M.","family":"Moreno Uribe","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-8120","authenticated-orcid":false,"given":"Aline L.","family":"Petrin","sequence":"additional","affiliation":[{"name":"University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026042513251093000_2025.12.29.25343144v3.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"2026042513251093000_2025.12.29.25343144v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(09)60695-4"},{"key":"2026042513251093000_2025.12.29.25343144v3.3","doi-asserted-by":"publisher","DOI":"10.1186\/s40510-016-0127-z"},{"key":"2026042513251093000_2025.12.29.25343144v3.4","doi-asserted-by":"publisher","DOI":"10.5152\/TurkJOrthod.2019.18094"},{"key":"2026042513251093000_2025.12.29.25343144v3.5","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23605"},{"key":"2026042513251093000_2025.12.29.25343144v3.6","doi-asserted-by":"publisher","DOI":"10.1177\/1055665620935363"},{"key":"2026042513251093000_2025.12.29.25343144v3.7","doi-asserted-by":"publisher","DOI":"10.1159\/000337464"},{"key":"2026042513251093000_2025.12.29.25343144v3.8","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.23605"},{"key":"2026042513251093000_2025.12.29.25343144v3.9","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e318189169b"},{"key":"2026042513251093000_2025.12.29.25343144v3.10","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0b013e31824f6480"},{"key":"2026042513251093000_2025.12.29.25343144v3.11","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000003820"},{"key":"2026042513251093000_2025.12.29.25343144v3.12","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_2000_037_0342_robccl_2.3.co_2"},{"key":"2026042513251093000_2025.12.29.25343144v3.13","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_2000_037_0342_robccl_2.3.co_2"},{"key":"2026042513251093000_2025.12.29.25343144v3.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2021.05.020"},{"key":"2026042513251093000_2025.12.29.25343144v3.15","doi-asserted-by":"publisher","DOI":"10.1177\/10556656211057368"},{"key":"2026042513251093000_2025.12.29.25343144v3.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(00)00314-0"},{"key":"2026042513251093000_2025.12.29.25343144v3.17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7139.1236"},{"key":"2026042513251093000_2025.12.29.25343144v3.18","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199001000-00010"},{"key":"2026042513251093000_2025.12.29.25343144v3.19","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22090"},{"key":"2026042513251093000_2025.12.29.25343144v3.20","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000009611"},{"key":"2026042513251093000_2025.12.29.25343144v3.21","first-page":"215","article-title":"Craniofacial growth in complete unilateral cleft lip and palate: a roentgeno-cephalometric study","volume":"13","year":"1976","journal-title":"Cleft Palate J"},{"key":"2026042513251093000_2025.12.29.25343144v3.22","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(19980827)79:1&lt;42::aid-ajmg11&gt;3.0.co;2-m"},{"key":"2026042513251093000_2025.12.29.25343144v3.23","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djae254"},{"key":"2026042513251093000_2025.12.29.25343144v3.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2005.12.003"},{"key":"2026042513251093000_2025.12.29.25343144v3.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0307-z"},{"key":"2026042513251093000_2025.12.29.25343144v3.26","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12747"},{"key":"2026042513251093000_2025.12.29.25343144v3.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2005.12.003"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.29.25343144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T20:25:21Z","timestamp":1777148721000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2025.12.29.25343144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":27,"URL":"https:\/\/doi.org\/10.64898\/2025.12.29.25343144","relation":{},"subject":[],"published":{"date-parts":[[2025,12,29]]},"subtype":"preprint"}}