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Objectives: To present descriptive epidemiology of Orofacial Clefts and to determine the association of syndromic forms with antenatal high-risk conditions, preterm birth, and comorbidities among nested-series of cases.

Methods: A study of nested-series of cases was conducted. Frequencies of cleft type, associated congenital anomalies, syndromic, non-syndromic and multiple malformation forms, and distribution of Orofacial Clefts according to sex and affected-side were determined. Odds ratios were calculated as measures of association between syndromic forms and antenatal high-risk conditions, preterm birth and comorbidities. A total of three hundred and eleven patients with Orofacial Clefts were assessed in a 12-month period.

Results: The most frequent type of Orofacial Clefts was cleft lip and palate, this type of cleft was more frequent in males, whereas cleft palate occurred more often in females. The most common cases occurred as non-syndromic forms. Aarskog-Scott syndrome showed the highest frequency amongst syndromic forms. Hypertensive disorders in pregnancy, developmental dysplasia of the hip, central nervous diseases and respiratory failure showed significant statistical associations (p <0.05) with syndromic forms.

Conclusions: These data provide an epidemiological reference of Orofacial Clefts in Colombia. Novel associations between syndromic forms and clinical variables are determined. In order to investigate causality relationships between these variables further studies must be carried out.

Arias Urueña, L., Briceño Balcazar, I., Martinez Lozano, J., Collins, A., & Uricoechea Patiño, D. A. (2024). Clinical aspects associated with syndromic forms of Orofacial Clefts in a Colombian population. Colombia Medica, 46(4), 162–167. (Original work published December 30, 2015)

Vanderas AP. Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review. Cleft Palate J. 1987;24(3):216–225.

Menegotto BG, Salzano FM. Epidemiology of oral clefts in a large South American sample. Cleft Palate Craniofac J. 1991;28(4):373–376.

Harville EW, Wilcox AJ, Lie RT, Vindenes H, Abyholm F. Cleft lip and palate versus cleft lip only: are they distinct defects? Am J Epidemiol. 2005;162(5):448–453.

Mossey PA, Modell B. Epidemiology of oral clefts 2012an international perspective. Front Oral Biol. 2012;16:1–18.

Stuppia L, Capogreco M, Marzo G, La Rovere D, Antonucci I, Gatta V, et al. Genetics of syndromic and nonsyndromic cleft lip and palate. J Craniofac Surg. 2011;22(5):1722–1726.

Jugessur A, Murray JC. Orofacial clefting: recent insights into a complex trait. Curr Opin Genet Dev. 2005;15(3):270–278.

Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12(3):167–178.

Mossey P. Epidemiology underpinning research in the aetiology of orofacial clefts. Orthod Craniofac Res. 2007;10(3):114–120.

Bell JC, Raynes-Greenow C, Bower C, Turner RM, Roberts CL, Nassar N. Descriptive epidemiology of cleft lip and cleft palate in Western Australia. Birth Defects Res A Clin Mol Teratol. 2013;97(2):101–108.

Milerad J, Larson O, Ph DD, Hagberg C, Ideberg M. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pt 1Pediatrics. 1997;100(2):180–186.

Cerón Zapata AM, López Palacio AM, Aristizábal Puerta GM, Uribe Álvarez C. A retrospective characterization study on patients with oral clefts in Medellín, Colombia, South America. Revista Facultad de Odontología Universidad de Antioquia. 2010;22:81–87.

Bedón M, Villota LG. Cleft lip and palate successful management trends. Arch Med. 2012;12

CDC [2013 June 29];Epi.Info 7.1.5. 2013. Available from:

Charry I, Aguirre M, Castaño Castrillón J, Gómez B, Higuera J, Mateus G, et al. Caracterización de los pacientes con labio y paladar hendido y de la atención brindada en el Hospital Infantil Universitario de Manizales (Colombia), 2010. Phys Rev Lett. 2014;12(2):7–7.

Fraser FC. The genetics of cleft lip and cleft palate. Am J Hum Genet. 1970;22(3):336–352. [PubMed]

Wyszynski DF, Beaty TH, Maestri NE. Genetics of nonsyndromic oral clefts revisited. Cleft Palate Craniofac J. 1996;33(5):406–417.

Rittler M, Cosentino V, Lopez-Camelo JS, Murray JC, Wehby G, Castilla EE. Associated anomalies among infants with oral clefts at birth and during a 1-year follow-up. Am J Med Genet A. 2011;7(96):10–10.

Zucchero TM, Cooper ME, Maher BS, Daack-Hirsch S, Nepomuceno B, Ribeiro L, et al. Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate. N Engl J Med. 2004;351(8):769–780.

Aarskog D. A familial syndrome of short stature associated with facial dysplasia and genital anomalies. J Pediatr. 1970;77(5):856–861.

Hoffman JD, Irons M, Schwartz CE, Medne L, Zackai EH. A newly recognized craniosynostosis syndrome with features of Aarskog-Scott and Teebi syndromes. Am J Med Genet A. 2007;15(12):1282–1286.

Orrico A, Galli L, Obregon MG, de Castro Perez MF.Falciani M.Sorrentino V Unusually severe expression of craniofacial features in Aarskog-Scott syndrome due to a novel truncating mutation of the FGD1 gene. Am J Med Genet A. 2007;143(1):58–63.

Zou W, Greenblatt MB, Shim JH, Kant S, Zhai B, Lotinun S, et al. MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice. J Clin Invest. 2011;121(11):4383–4392.

Calzolari E, Pierini A, Astolfi G, Bianchi F, Neville AJ, Rivieri F. Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries. Am J Med Genet A. 2007;143(6):528–537.

Hwang SJ, Beaty TH, McIntosh I, Hefferon T, Panny SR. Association between homeobox-containing gene MSX1 and the occurrence of limb deficiency. Am J Med Genet. 1998;75(4):419–423.

Sekhon PS, Ethunandan M, Markus AF, Krishnan G, Rao CB. Congenital anomalies associated with cleft lip and palate-an analysis of 1623 consecutive patients. Cleft Palate Craniofac J. 2011;48(4):371–378.

Wyszynski DF, Sarkozi A, Czeizel AE. Oral clefts with associated anomalies: methodological issues. Cleft Palate Craniofac J. 2006;43(1):1–6.

Bueno DF, Sunaga DY, Kobayashi GS, Aguena M, Raposo-Amaral CE, Masotti C, et al. Human stem cell cultures from cleft lip/palate patients show enrichment of transcripts involved in extracellular matrix modeling by comparison to controls. Stem Cell Rev. 2011;7(2):446–457.

Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. Am J Med Genet C Semin Med Genet. 2013;4:246–258.

Higgins JR, Papayianni A, Brady HR, Darling MR, Walshe JJ. Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia. Am J Obstet Gynecol. 1998;179(2):464–469.

Young BC, Levine RJ, Karumanchi SA. Pathogenesis of preeclampsia. Annu Rev Pathol. 2010;5:173–192. [PubMed]

Ji L, Brkic J, Liu M, Fu G, Peng C, Wang YL. Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med. 2013;34(5):981–1023.

Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003;69(1):1–7.

Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123(24):2856–2869.

Vicovac L, Aplin JD. Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat. 1996;156(3):202–216.

Goldman-Wohl D, Yagel S. Regulation of trophoblast invasion: from normal implantation to pre-eclampsia. Mol Cell Endocrinol. 2002;187(1-2):233–238.

Degitz SJ, Morris D, Foley GL, Francis BM. Role of TGF-beta in RA-induced cleft palate in CD-1 mice. Teratology. 1998;58(5):197–204.

Salonen Ros H, Lichtenstein P, Lipworth L, Cnattingius S. Genetic effects on the liability of developing pre-eclampsia and gestational hypertension. Am J Med Genet. 2000;91(4):256–260.

Stanier P, Moore GE. Genetics of cleft lip and palatesyndromic genes contribute to the incidence of non-syndromic clefts. Hum Mol Genet. 2004;13(Spec No 1):R73–R81.

Wilson ML, Desmond DH, Goodwin TM, Miller DA, Ingles SA. Maternal and fetal variants in the TGF-beta3 gene and risk of pregnancy-induced hypertension in a predominantly Latino population. Am J Obstet Gynecol. 2009;201(3):22–22.

Osoegawa K, Vessere GM, Utami KH, Mansilla MA, Johnson MK, Riley BM, et al. Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation. J Med Genet. 2008;45(2):81–86.

Cohen MM, Jr The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A. 2006;140(23):2646–2706.

Shi D, Dai J, Ikegawa S, Jiang Q. Genetic study on developmental dysplasia of the hip. Eur J Clin Invest. 2012;42(10):1121–1125.

Desalu I, Adeyemo W, Akintimoye M, Adepoju A. Airway and respiratory complications in children undergoing cleft lip and palate repair. Ghana Med J. 2010;44(1):16–20.

Paladini D. Fetal micrognathia: almost always an ominous finding: Ultrasound Obstet. Gynecol. 2010;35(4):377–384.


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Received 2014-10-03
Accepted 2015-12-14
Published 2024-06-14