{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:38:05Z","timestamp":1787499485968,"version":"build-2736575974"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE016148 R01DE027023"],"award-info":[{"award-number":["R01DE016148 R01DE027023"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Nonsyndromic orofacial clefts belong to a class of congenital malformations characterized by a complex and multifactorial etiology. During early facial development, multiple factors can disrupt fusion leading to a cleft; this includes the shape of the embryonic face. The face shape hypothesis (FSH) of orofacial clefting emerged in the 1960s, influenced by morphological differences observed within affected families, comparative studies of mouse models, and advances in modeling genetic liability for complex traits in populations. For the past five decades, studies have documented changes in the shape or spatial arrangement of facial prominences in embryonic mice and altered post-natal facial shape in individuals at elevated risk for orofacial clefting due to their family history. Moreover, recent studies showing how genes that impact facial shape in humans and mice are providing clues about the genetic basis of orofacial clefting. In this review, I discuss the origins of the FSH, provide an overview of the supporting evidence, and discuss ways in which the FSH can inform our understanding of orofacial clefting.<\/jats:p>","DOI":"10.3389\/fgene.2022.891502","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T02:48:13Z","timestamp":1651546093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["What\u2019s Shape Got to Do With It? Examining the Relationship Between Facial Shape and Orofacial Clefting"],"prefix":"10.3389","volume":"13","author":[{"given":"Seth M.","family":"Weinberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"B1","first-page":"337","article-title":"Craniofacial Variability in Parents of Children with Cleft Lip and Cleft Palate","volume":"23","author":"AlEmran","year":"1999","journal-title":"J. Clin. Pediatr. Dent."},{"key":"B2","first-page":"13","article-title":"Cleft Lip and Cleft Palate: Cephalometric Characteristics of Affected Individuals, Their Relatives and a Control Population","volume":"120","author":"Blanco","year":"1992","journal-title":"Rev. Med. Chil."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1038\/ejhg.2011.110","article-title":"Genetic Determination of Human Facial Morphology: Links between Cleft-Lips and Normal Variation","volume":"19","author":"Boehringer","year":"2011","journal-title":"Eur. J. Hum. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1111\/j.1469-7580.2008.00999.x","article-title":"Short-faced Mice and Developmental Interactions between the Brain and the Face","volume":"213","author":"Boughner","year":"2008","journal-title":"J. Anat."},{"key":"B5","first-page":"1","article-title":"Sexual Differences in Closure of the Human Palatal Shelves","volume":"6","author":"Burdi","year":"1969","journal-title":"Cleft Palate J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1597\/03-090.1","article-title":"Predisposing Factors to Formation of Cleft Lip and Palate: Inherited Craniofacial Skeletal Morphology","volume":"41","author":"Chatzistavrou","year":"2004","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B7","first-page":"341","article-title":"Racial Differences in Cephalometric Measurements and Incidence of Cleft Lip with or without Cleft Palate","volume":"5","author":"Chung","year":"1985","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"B8","first-page":"369","article-title":"A Comparative Study of Development during Primary Palate Formation in A\/WySn, C57BL\/6, and Their F1 Crosses","volume":"6","author":"Ciriani","year":"1986","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-018-0057-4","article-title":"Genome-wide Mapping of Global-To-Local Genetic Effects on Human Facial Shape","volume":"50","author":"Claes","year":"2018","journal-title":"Nat. Genet."},{"key":"B10","first-page":"28","article-title":"Craniofacial Morphology of Parents with and without Cleft Lip and Palate Children","volume":"9","author":"Coccaro","year":"1972","journal-title":"Cleft Palate J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"131","DOI":"10.2307\/2984646","article-title":"Multifactorial Models for Familial Diseases in Man","volume":"138","author":"Curnow","year":"1975","journal-title":"J. R. Stat. Soc. Ser. A General."},{"key":"B12","doi-asserted-by":"publisher","first-page":"100025","DOI":"10.1016\/j.xhgg.2021.100025","article-title":"The PAX1 Locus at 20p11 Is a Potential Genetic Modifier for Bilateral Cleft Lip","volume":"2","author":"Curtis","year":"2021","journal-title":"Hum. Genet. Genomics Adv."},{"key":"B13","first-page":"247","article-title":"A Comparative Study of Craniofacial Growth during Secondary Palate Development in Four Strains of Mice","volume":"2","author":"Diewert","year":"1982","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"B14","first-page":"178","article-title":"Abnormalities of the Teeth and Supporting Structures in Children with Clefts of Lip and Palate","volume-title":"The Causes and Natural History of Cleft Lip and Palate","author":"Dixon","year":"1966"},{"key":"B15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1469-1809.1974.tb01995.x","article-title":"Facial and Oral Form in Sibs of Children with Cleft Lip with or without Cleft Palate","volume":"38","author":"Erickson","year":"1974","journal-title":"Ann. Hum. Genet."},{"key":"B16","first-page":"351","article-title":"Nostril Asymmetry: Microform of Cleft Lip Palate? an Anthropometrical Study of Healthy North American Caucasians","volume":"16","author":"Farkas","year":"1979","journal-title":"Cleft Palate J."},{"key":"B17","volume-title":"A System of Practical Surgery","author":"Fergusson","year":"1870"},{"key":"B18","first-page":"247","article-title":"Cephalometric Study of Families with Clefts","volume":"16","author":"Figalov\u00e1","year":"1974","journal-title":"Acta Chir. Plast."},{"key":"B19","first-page":"336","article-title":"The Genetics of Cleft Lip and Cleft Palate","volume":"22","author":"Fraser","year":"1970","journal-title":"Am. J. Hum. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1136\/jmg.7.2.112","article-title":"Relation of Face Shape to Susceptibility to Congenital Cleft Lip. A Preliminary Report","volume":"7","author":"Fraser","year":"1970","journal-title":"J. Med. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/tera.1420140302","article-title":"The Multifactorial\/threshold Concept-Uses and Misuses","volume":"14","author":"Fraser","year":"1976","journal-title":"Teratology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1542\/peds.19.4.782","article-title":"Experimental Production of Congenital Cleft Palate: Genetic and Environmental Factors","volume":"19","author":"Fraser","year":"1957","journal-title":"Pediatrics"},{"key":"B23","first-page":"234","article-title":"Genetic Consideration on the Dysplasia of the Nasopalatal Segments as a \"Formes Frustes\" Radiologically Found in Parents of Cleft Children: a Preliminary Report","volume":"7","author":"Fukuhara","year":"1962","journal-title":"Jpn. J. Hum. Genet."},{"key":"B24","first-page":"333","article-title":"Possible Carrier Status of Hereditary Cleft Palate with Cleft Lip: Report of Cases","volume":"10","author":"Fukuhara","year":"1963","journal-title":"Bull. Tokyo Med. Dent. Univ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1002\/bdr2.1830","article-title":"Environmental Mechanisms of Orofacial Clefts","volume":"112","author":"Garland","year":"2020","journal-title":"Birth Defects Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1242\/dmm.017616","article-title":"Tfap2a-dependent Changes in Mouse Facial Morphology Result in Clefting that Can Be Ameliorated by a Reduction in Fgf8 Gene Dosage","volume":"8","author":"Green","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1002\/dvdy.110","article-title":"Nonlinear Gene Expression\u2010phenotype Relationships Contribute to Variation and Clefting in the A\/WySn Mouse","volume":"248","author":"Green","year":"2019","journal-title":"Dev. Dyn."},{"key":"B28","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/j.0021-8782.2004.00356.x","article-title":"Craniofacial Variability and Morphological Integration in Mice Susceptible to Cleft Lip and Palate","volume":"205","author":"Hallgrimsson","year":"2004","journal-title":"J. Anat."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e1007501","DOI":"10.1371\/journal.pgen.1007501","article-title":"Investigating the Shared Genetics of Non-syndromic Cleft Lip\/palate and Facial Morphology","volume":"14","author":"Howe","year":"2018","journal-title":"PLoS Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"626403","DOI":"10.3389\/fgene.2021.626403","article-title":"The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation","volume":"12","author":"Indencleef","year":"2021","journal-title":"Front. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3389\/fgene.2018.00502","article-title":"Six NSCL\/P Loci Show Associations with Normal-Range Craniofacial Variation","volume":"9","author":"Indencleef","year":"2018","journal-title":"Front. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1002\/tera.1420450410","article-title":"Morphometric Analysis of Heterozygote Dancer Mice Predisposed to 6-Aminonicotinamide-Induced Cleft Lip","volume":"45","author":"Jacobson","year":"1992","journal-title":"Teratology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1002\/bdr2.1768","article-title":"Cellular and Developmental Basis of Orofacial Clefts","volume":"112","author":"Ji","year":"2020","journal-title":"Birth Defects Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1002\/dvdy.20646","article-title":"Development of the Upper Lip: Morphogenetic and Molecular Mechanisms","volume":"235","author":"Jiang","year":"2006","journal-title":"Dev. Dyn."},{"key":"B35","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/tera.1420140106","article-title":"Test of the Hypothesis that Embryonic Face Shape Is a Causal Factor in Genetic Predisposition to Cleft Lip in Mice","volume":"14","author":"Juriloff","year":"1976","journal-title":"Teratology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13293-016-0076-8","article-title":"Using the 3D Facial Norms Database to Investigate Craniofacial Sexual Dimorphism in Healthy Children, Adolescents, and Adults","volume":"7","author":"Kesterke","year":"2016","journal-title":"Biol. Sex. Differ."},{"key":"B37","doi-asserted-by":"publisher","first-page":"163","DOI":"10.5005\/jp-journals-10005-1072","article-title":"Evaluation of Parental Nasomaxillary Asymmetry as a Risk Factor for Development of Palatal Clefts in Their Offsprings","volume":"3","author":"Kumar S","year":"2010","journal-title":"Int. J. Clin. Pediatr. Dent."},{"key":"B38","first-page":"702","article-title":"Facial Morphology as an Indicator of Genetic Predisposition to Cleft Lip and Palate","volume":"26","author":"Kurisu","year":"1974","journal-title":"Am. J. Hum. Genet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1597\/1545-1569_1996_033_0096_cmitwc_2.3.co_2","article-title":"Craniofacial Morphology in Twins with Cleft Lip and Palate","volume":"33","author":"Laatikainen","year":"1996","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14109","article-title":"Genetic Models and Approaches to Study Orofacial Clefts","author":"Leslie","year":"2021","journal-title":"Oral Dis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ajhg.2015.01.004","article-title":"Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or Near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci","volume":"96","author":"Leslie","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/bdra.20656","article-title":"Cleft Lip and Palate Results from Hedgehog Signaling Antagonism in the Mouse: Phenotypic Characterization and Clinical Implications","volume":"88","author":"Lipinski","year":"2010","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e102603","DOI":"10.1371\/journal.pone.0102603","article-title":"Characterization of Subtle Brain Abnormalities in a Mouse Model of Hedgehog Pathway Antagonist-Induced Cleft Lip and Palate","volume":"9","author":"Lipinski","year":"2014","journal-title":"PLoS One"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e1002932","DOI":"10.1371\/journal.pgen.1002932","article-title":"A Genome-wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans","volume":"8","author":"Liu","year":"2012","journal-title":"PLoS Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4771","DOI":"10.1038\/s41598-018-22752-5","article-title":"Modelling 3D Craniofacial Growth Trajectories for Population Comparison and Classification Illustrated Using Sex-Differences","volume":"8","author":"Matthews","year":"2018","journal-title":"Sci. Rep."},{"key":"B46","first-page":"16","article-title":"The Craniofacial Morphology of the Parents of Children with Cleft Lip And\/or Palate: a Review of Cephalometric Studies","volume":"8","author":"Maulina","year":"2006","journal-title":"Stomatologija"},{"key":"B47","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1093\/ejo\/cjp067","article-title":"Asymmetry of the Craniofacial Skeleton in the Parents of Children with a Cleft Lip, with or without a Cleft Palate, or an Isolated Cleft Palate","volume":"32","author":"McIntyre","year":"2010","journal-title":"Eur. J. Orthod."},{"key":"B48","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1093\/ortho\/29.4.299","article-title":"Asymmetry of the Parental Craniofacial Skeleton in Orofacial Clefting","volume":"29","author":"McIntyre","year":"","journal-title":"J. Orthod."},{"key":"B49","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1093\/ejo\/26.4.375","article-title":"Parental Craniofacial Morphology in Orofacial Clefting","volume":"26","author":"McIntyre","year":"2004","journal-title":"Eur. J. Orthod."},{"key":"B50","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1597\/1545-1569(2003)040<0416:pcaotp>2.0.co;2","article-title":"Posteroanterior Cephalometric Analysis of the Parental Craniofacial Morphology in Orofacial Clefting","volume":"40","author":"McIntyre","year":"2003","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/ortho\/29.1.23","article-title":"The Craniofacial Morphology of the Parents of Children with Orofacial Clefting: a Systematic Review of Cephalometric Studies","volume":"29","author":"McIntyre","year":"","journal-title":"J. Orthod."},{"key":"B52","first-page":"17","article-title":"Sippenuntersuchegen bei Lippen, Kiefer, und Gaumenspalte","volume":"23","author":"Mengel","year":"1939","journal-title":"Zeits. F. Konstlehre"},{"key":"B53","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1111\/joa.12182","article-title":"Exploratory Genotype-Phenotype Correlations of Facial Form and Asymmetry in Unaffected Relatives of Children with Non-syndromic Cleft Lip And\/or Palate","volume":"224","author":"Miller","year":"2014","journal-title":"J. Anat."},{"key":"B54","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/aja.1001640104","article-title":"Developmental Alterations Associated with Spontaneous Cleft Lip and Palate in CL\/Fr Mice","volume":"164","author":"Millicovsky","year":"1982","journal-title":"Am. J. Anat."},{"key":"B55","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1043\/0003-3219(1968)038<0199:MOAFDI>2.0.CO;2","article-title":"Minor Oral and Facial Defects in Relatives of Oral Cleft Patients","volume":"38","author":"Mills","year":"1968","journal-title":"Angle Orthod."},{"key":"B56","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1597\/1545-1569(1997)034<0027:dbclwo>2.3.co;2","article-title":"Differentiation between Cleft Lip with or without Cleft Palate and Isolated Cleft Palate Using Parental Cephalometric Parameters","volume":"34","author":"Mossey","year":"1997","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/s0266-4356(98)90498-3","article-title":"Cephalometric Features in the Parents of Children with Orofacial Clefting","volume":"36","author":"Mossey","year":"1998","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"B58","first-page":"193","article-title":"Size of the Cranium in Parents and Their Children with Cleft Lip","volume":"21","author":"Nakasima","year":"1984","journal-title":"Cleft Palate J."},{"key":"B59","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/0002-9416(83)90178-1","article-title":"Characteristics of Craniofacial Structures of Parents of Children with Cleft Lip And\/or Palate","volume":"84","author":"Nakasima","year":"1983","journal-title":"Am. J. Orthod."},{"key":"B60","article-title":"Decoding the Human Face: Challenges and Progress in Understanding the Genetics of Craniofacial Morphology","author":"Naqvi","year":"","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/0003-9969(68)90017-4","article-title":"Laminographic X-Ray Studies in Families with Cleft Lip and Cleft Palate","volume":"13","author":"Niswander","year":"1968","journal-title":"Archives Oral Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1111\/j.1469-7580.2007.00845.x","article-title":"Phenotypic Variability and Craniofacial Dysmorphology: Increased Shape Variance in a Mouse Model for Cleft Lip","volume":"212","author":"Parsons","year":"2008","journal-title":"J. Anat."},{"key":"B63","first-page":"185","article-title":"Nostril Asymmetry Not a Microform of Cleft Lip","volume":"8","author":"Pashayan","year":"1971","journal-title":"Cleft Palate J."},{"key":"B64","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1597\/1545-1569_2003_040_0397_aodcfi_2.0.co_2","article-title":"Association of Distinct Craniofacial Features in Nonsyndromic Cleft Lip and Palate Family Members","volume":"40","author":"Perkiomaki","year":"2003","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B65","first-page":"194","article-title":"Craniofacial Morphological Features in Parents of Children with Isolated Cleft Palate","volume":"28","author":"Proch\u00e1zkov\u00e1","year":"1986","journal-title":"Acta Chir. Plast."},{"key":"B66","first-page":"162","article-title":"Craniofacial Morphology as a Marker of Predisposition to Isolated Cleft Palate","volume":"15","author":"Proch\u00e1zkov\u00e1","year":"1995","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1043\/0003-3219(1994)064<0137:CPOPOC>2.0.CO;2","article-title":"Craniofacial Pattern of Parents of Children Having Cleft Lip And\/or Cleft Palate Anomaly","volume":"64","author":"Raghavan","year":"1994","journal-title":"Angle Orthod."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2886","DOI":"10.1002\/ajmg.a.38471","article-title":"Testing the Face Shape Hypothesis in Twins Discordant for Nonsyndromic Orofacial Clefting","volume":"173","author":"Roosenboom","year":"2017","journal-title":"Am. J. Med. Genet."},{"key":"B69","volume-title":"On Harelip and Cleft Palate","author":"Rose","year":"1891"},{"key":"B70","first-page":"548","article-title":"The Radiological Appearance of the Nasal Fossas in the Ancestors and Immediate Relations of Subjects with Cleft Palate. Preliminary Note","volume":"15","author":"Rusconi","year":"1966","journal-title":"Minerva Stomatol."},{"key":"B71","first-page":"1479","article-title":"Craniofacial Morphology of Parents with Cleft Lip and Palate Children","volume":"89","author":"Sato","year":"1989","journal-title":"Shikwa Gakuho"},{"key":"B72","first-page":"31","article-title":"A Cephalometric Study of Craniofacial Morphology of Parents of Children with Cleft Lip and Palate [in Japanese]","volume":"3","author":"Shibasaki","year":"1978","journal-title":"J. Jpn. Cleft Palate Assoc."},{"key":"B73","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1597\/1545-1569_1999_036_0139_ndamcl_2.3.co_2","article-title":"Nasal Deformity and Microform Cleft Lip in Parents of Patients with Cleft Lip","volume":"36","author":"Sigler","year":"1999","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B74","first-page":"371","article-title":"Width of the Craniofacial Complex during Formation of the Secondary Palate","volume":"8","author":"Smiley","year":"1971","journal-title":"Cleft Palate J."},{"key":"B75","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/ar.1091950201","article-title":"Phenytoin (Dilantin)-induced Cleft Lip and Palate in A\/J Mice: a Scanning and Transmission Electron Microscopic Study","volume":"195","author":"Sulik","year":"1979","journal-title":"Anat. Rec."},{"key":"B76","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1597\/1545-1569_1999_036_0131_dmipoc_2.3.co_2","article-title":"Dentocraniofacial Morphology in Parents of Children with Cleft Lip And\/or Palate","volume":"36","author":"Suzuki","year":"1999","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/tera.1420190210","article-title":"Newborn and Adult Face Shapes Related to Mouse Cleft Lip Predisposition","volume":"19","author":"Trasler","year":"1979","journal-title":"Teratology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/tera.1420280112","article-title":"Ultrastructure of Initial Nasal Process Cell Fusion in Spontaneous and 6-Aminonicotinamide-Induced Mouse Embryo Cleft Lip","volume":"28","author":"Trasler","year":"1983","journal-title":"Teratology"},{"key":"B79","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/tera.1420010106","article-title":"Pathogenesis of Cleft Lip and its Relation to Embryonic Face Shape in A\/J and C57BL Mice","volume":"1","author":"Trasler","year":"1968","journal-title":"Teratology"},{"key":"B80","first-page":"445","article-title":"Sistens Plura Exempla Palati Deficientis","volume":"1","author":"Trew","year":"1757","journal-title":"Nova Acta Physico-Medica Acad. Caesareae Leopoldino-Carolinae Naturae Curiosorum"},{"key":"B81","first-page":"141","article-title":"A Morphometric Analysis of Craniofacial Growth in Cleft Lip and Noncleft Mice","volume":"12","author":"Wang","year":"1992","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"B82","first-page":"318","article-title":"A Study of Cephalometric Features in Cleft Lip-Cleft Palate Families. I: Phenotypic Heterogeneity and Genetic Predisposition in Parents of Sporadic Cases","volume":"26","author":"Ward","year":"1989","journal-title":"Cleft Palate J."},{"key":"B83","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/oso\/9780195139068.003.0007","article-title":"Morphometric Characteristics of Subjects with Oral Facial Clefts and Their Relatives","volume-title":"Cleft Lip and Palate: From Origin to Treatment","author":"Ward","year":"2002"},{"key":"B84","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/ajmg.1320500113","article-title":"Cephalometric Evidence for a Dominantly Inherited Predisposition to Cleft Lip-Cleft Palate in a Single Large Kindred","volume":"50","author":"Ward","year":"1994","journal-title":"Am. J. Med. Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.1601-6343.2006.00339.x","article-title":"Parental Craniofacial Morphology in Cleft Lip with or without Cleft Palate as Determined by Cephalometry: a Meta-Analysis","volume":"9","author":"Weinberg","year":"2006","journal-title":"Orthod. Craniofac Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1002\/ajmg.a.32177","article-title":"Three-dimensional Morphometric Analysis of Craniofacial Shape in the Unaffected Relatives of Individuals with Nonsyndromic Orofacial Clefts: a Possible Marker for Genetic Susceptibility","author":"Weinberg","year":"2008","journal-title":"Am. J. Med. Genet."},{"key":"B87","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1601-6343.2009.01462.x","article-title":"Face Shape of Unaffected Parents with Cleft Affected Offspring: Combining Three-Dimensional Surface Imaging and Geometric Morphometrics","volume":"12","author":"Weinberg","year":"2009","journal-title":"Orthod. Craniofacial Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41588-020-00741-7","article-title":"Insights into the Genetic Architecture of the Human Face","volume":"53","author":"White","year":"2021","journal-title":"Nat. Genet."},{"key":"B89","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1093\/genetics\/19.6.506","article-title":"An Analysis of Variability in Number of Digits in an Inbred Strain of Guinea Pigs","volume":"19","author":"Wright","year":"","journal-title":"Genetics"},{"key":"B90","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1093\/genetics\/19.6.537","article-title":"The Results of Crosses between Inbred Strains of guinea Pigs, Differing in Number of Digits","volume":"19","author":"Wright","year":"","journal-title":"Genetics"},{"key":"B91","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1597\/1545-1569_2003_040_0493_aonaic_2.0.co_2","article-title":"Association of Nasomaxillary Asymmetry in Children with Unilateral Cleft Lip and Palate and Their Parents","volume":"40","author":"Yoon","year":"2003","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B92","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1597\/02-134.1","article-title":"Transverse Craniofacial Features and Their Genetic Predisposition in Families with Nonsyndromic Unilateral Cleft Lip and Palate","volume":"41","author":"Yoon","year":"2004","journal-title":"Cleft Palate-Craniofacial J."},{"key":"B93","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/ar.20415","article-title":"Comparative Morphometrics of Embryonic Facial Morphogenesis: Implications for Cleft-Lip Etiology","volume":"290","author":"Young","year":"2007","journal-title":"Anat. Rec."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac037","article-title":"Polygenic Risk Impacts PDGFRA Mutation Penetrance in Non-syndromic Cleft Lip and Palate","author":"Yu","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1002\/ajmg.a.38688","article-title":"Soft Tissue Nasal Asymmetry as an Indicator of Orofacial Cleft Predisposition","volume":"176","author":"Zhang","year":"2018","journal-title":"Am. J. Med. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.891502\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T18:35:20Z","timestamp":1700505320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.891502\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,3]]},"references-count":95,"alternative-id":["10.3389\/fgene.2022.891502"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.891502","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,3]]},"article-number":"891502"}}