Cleft lip and/or palate (CL/P) represent one of the most common congenital malformations in the oral and maxillofacial region, and various factors are associated with the development of CL/P and its subtypes. Despite an increased concordance rate in monozygotic twins, mirror-image cleft formations represent a very rare phenotype, for which only very few case reports exist in the literature. The present case report describes a female pair of monozygotic twins from Germany who were born with mirror-image bilateral complete and incomplete cleft lip and alveolus.
MosseyPAModellB. Epidemiology of oral clefts 2012: An international perspective. Front Oral Biol. 2012;16:1-18. doi:10.1159/000337464
2.
Genisca AE, Frías JL, Broussard CS, Honein MA, Lammer EJ, Moore CA, Shaw GM, Murray JC, Yang W, Rasmussen SA.Orofacial clefts in the National Birth Defects Prevention Study, 1997–2004. Am J Med Genet A.2009;149a(6):1149-1158. doi:10.1002/ajmg.a.32854.
3.
Ács M, Cavalcante BGN, Bănărescu M, Wenning AS, Hegyi P, Szabó B, Harnos A, Gerber G, Varga G.Maternal factors increase risk of orofacial cleft: A meta-analysis. Sci Rep. 2024;14(1):28104. doi:10.1038/s41598-024-79346-7
4.
Proctor-WilliamsKLouwB. Cleft lip and/or palate in infants prenatally exposed to opioids. Cleft Palate Craniofac J. 2022;59(4):513-521. doi:10.1177/10556656211013687
5.
AlrbataRHAlmaaitehHYAlbdourMNAlshammoutRW. A retrospective cohort study to evaluate the association between types of nonsyndromic oral clefts and a child's gender and maternal age. J Int Soc Prev Community Dent. 2021;11(1):92-97. doi:10.4103/jispcd.JISPCD_399_20
6.
XuD-PQuW-dSunCCaoR-YLiuD-wDuP-g. A study on environmental factors for nonsyndromic cleft lip and/or palate. J Craniofac Surg. 2018;29(2):364–367.
7.
CriderKSQiYPYeungLF, Mai CT, Head Zauche L, Wang A, Daniels K, Williams JL. Folic acid and the prevention of birth defects: 30 years of opportunity and controversies. Annu Rev Nutr. 2022;42:423-452. doi:10.1146/annurev-nutr-043020-091647
8.
CaoWLiCSunF, Danilack VA, Saldanha IJ, Shi Y, Ji Y, Lin H, Ni M, Liu R, Sun S, Chang C. Association between maternal sexually transmitted diseases and birth defects in the United States: A nationwide population-based study. Ann Epidemiol. 2025;110:172-177. doi:10.1016/j.annepidem.2025.09.004
9.
ChengXDuFLongXHuangJ. Genetic inheritance models of non-syndromic cleft lip with or without palate: From monogenic to polygenic. Genes (Basel). 2023;14(10):1859. doi:10.3390/genes14101859.
10.
LudwigKUMangoldEHermsS, Nowak S, Reutter H, Paul A, Becker J, Herberz R, AlChawa T, Nasser E, et al.Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nat Genet. 2012;44(9):968-971. doi:10.1038/ng.2360
11.
TanE-CLimH-WLimECPLeeS-T. A novel interferon regulatory factor 6 mutation in an Asian family with Van der Woude syndrome. Cleft Palate Craniofac J. 2017;54(4):442-445. doi:10.1597/15-327
12.
HammondNLDixonMJ. Revisiting the embryogenesis of lip and palate development. Oral Dis. 2022;28(5):1306-1326. doi:10.1111/odi.14174
13.
BurdiARFaistK. Morphogenesis of the palate in normal human embryos with special emphasis on the mechanisms involved. Am J Anat. 1967;120(1):149-159. doi:10.1002/aja.1001200112
Maarse W, Bergé SJ, Pistorius L, van Barneveld T, Kon M, Breugem C, Mink van der Molen AB., Diagnostic accuracy of transabdominal ultrasound in detecting prenatal cleft lip and palate: A systematic review. Ultrasound Obstet Gynecol. 2010;35(4):495-502. doi:10.1002/uog.7472
16.
GrosenDBilleCPetersenI, Skytthe A, Hjelmborg Jv, Pedersen JK, Murray JC, Christensen K., Risk of oral clefts in twins. Epidemiology. 2011;22(3):313-319. doi:10.1097/EDE.0b013e3182125f9c
ThackerDGruberPJWeinbergPMCohenMS. Heterotaxy syndrome with mirror image anomalies in identical twins. Congenit Heart Dis. 2009;4(1):50-53. doi:10.1111/j.1747-0803.2008.00229.x
20.
SatohKShibataYTokushigeHOnizukaT. A mirror image of the first and second branchial arch syndrome associated with cleft lip and palate in monozygotic twins. Br J Plast Surg. 1995;48(8):601-605. doi:10.1016/0007-1226(95)90052-7
21.
FauzdarAChowdhryMMakrooRN, Mishra M, Srivastava P, Tyagi R, Bhadauria P, Kaul A., Rapid-prenatal diagnosis through fluorescence in situ hybridization for preventing aneuploidy related birth defects. Indian J Hum Genet. 2013;19(1):32-42. doi:10.4103/0971-6866.112881
22.
VoigtMFuschCOlbertzD, Hartmann K, Rochow N, Renken C, Schneider KTM., Analyse des Neugeborenenkollektivs der Bundesrepublik Deutschland. Analysis of the Neonatal Collective in the Federal Republic of Germany. 12 Mitteilung: Vorstellung engmaschiger Perzentilwerte (-kurven) für die Körpermaße Neugeborener. 2006/10/26 2006;66(10):956-970. doi:10.1055/s-2006-924458.
23.
MansillaMAKimaniJMitchellLE, Christensen K, Boomsma DI, Daack-Hirsch S, Nepomucena B, Wyszynski DF, Felix TM, Martin NG, et al.Discordant MZ twins with cleft lip and palate: A model for identifying genes in complex traits. Twin Res Hum Genet.2012;8(1):39-46. doi:10.1375/twin.8.1.39
24.
YanSFuFLiR, Yu Q, Li F, Zhou H, Wang Y, Huang R, Ma C, Guo F, et al.Exome sequencing improves genetic diagnosis of congenital orofacial clefts. Front Genet. 2023;14:1252823. doi:10.3389/fgene.2023.1252823
25.
HallJG. Twins and twinning. Am J Med Genet.1996;61(3):202-204. doi:10.1002/(SICI)1096-8628(19960122)61:3<202::AID-AJMG2>3.0.CO;2-W