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A Retrospective study on Recognizable Syndromes associated with craniofacial clefts

Betty Anna Jose, Subramani S A, Varsha Mokhasi, Shashirekha M

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Objective: There are about 300 to 600 syndromes associated with clefts in the craniofacial region. The cleft lip, cleft palate and cleft lip palate are the most common clefts seen in the craniofacial region. Sometimes these clefts are associated with other anomalies which are known as syndromic clefts. The objective of this study is to identify the syndromes associated with the clefts in the craniofacial region. Materials & methods: This retrospective study consists of  270 cases of clefts in the craniofacial region. The detailed case history including the maternal history, antenatal, natal, perinatal history and family history were taken from the patients and their parents.  Based on the clinical examination, radiological findings and genetic analysis  the different syndromes were identified. Results: 18 syndromic clefts were identified which belong to 10 different syndromes. It shows 6.67% of clefts are syndromic and remaining are nonsyndromic clefts. Conclusion: Median cleft face syndrome, Van der woude syndrome and Pierre Robin sequence are the common syndromes associated with the clefts in the craniofacial region.


Syndrome, Clefts, Anomalies, Craniofacial Region, Malformation

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Atasu M, Biren S. Ellis-van Creveld syndrome: Dental, clinical, genetics, and dermatoglyphic finding of a case. J ClinPaediatr Dent. 2000;24:141–5

Aziza A, Kandasamy R, Shazia S. Pattern of craniofacial anomalies seen in a tertiary care hospital in Saudi Arabia. Annals of Saudi Medicine.2011;31(5):488-493

Bader I, Khan NZ. Frontonasal dysplasia (FND) with bilateral anophthalmia: A case report with review of literature. Pak J Med Sci. 2005; 21:82–4.

Bhavna Kaul, Nanika Mahajan, Rakesh Gupta, Bhanu Kotwal. The syndrome of pit of the lower lip and its association with cleft palate. Contemp Clin Dent. 2014 Jul-Sep; 5(3): 383–385

Cohen MM., Jr . Cleft lip and palate: From origin to treatment. New York: Oxford University Press; 2002. Syndromes with orofacial clefting; pp. 53–65.

Dubey AK, Gupta RK. Treacher Collins syndrome: A report on two cases. MJAFI. 2006;58:67–8.

Das D, Das G, Ellis van Creveld syndrome with unusual association of essential infantile esotropia. Oman J Ophthalmol. 2010 Jan-Apr; 3(1): 23–25

Fox JW, Golden GT, Edgerton MT. Frontonasal dysplasia with alar clefts in two sisters. Genetic considerations and surgical correction. Plast Reconstr Surg. 1976;57:553–61.

FitzPatrick DR, Carr IM, McLaren L et al: Identification of SATB2 as the cleft palate gene on 2q32–q33. Hum Mol Genet 2003; 12: 2491–2501.

Goodman RM, Gorlin RJ. The malformed infant and child-An illustrative guide. Oxford, England: Oxford University; 1983. P. 262.

Ghassibe M, Bayet B, Revencu N, Verellen-Dumoulin C, Gillerot Y, Vanwijck R, Vikkula M. Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population. European Journal of Human Genetics (2005) 13, 1239–1242

Hertle RW, Ziylan S, Katowitz J. Ophthalmic features and visual prognosis in the Treacher-Collins syndrome. Br J Ophthalmol. 1993;77:642–5.

Hercilo M, Marcelo R, Mario SO, Roseli TM. Clinical and Genetic Features of Van der Woude Syndromes in Two large families in Brazil. Cleft Palate Craniofac J. 2007;44:239–43

Jensen BL, Kreiborg S, Dahl E, Fogh-Andersen P. Cleft lip and palate in Denmark, 1976-1981: epidemiology, variability, and early somatic development. Cleft Palate J. 1988; 25 : 258–69

Jones MC: Etiology of facial clefts: prospective evaluation of 428 patients. Cleft Palate J 1988; 25: 16–20.

Jones K L, Jones MC, Campo M. Smith’s Recognizable Patterns of Human Malformation. 7th ed.Philadelphia:Elsevier saunders;2013.

Kamal R, Dahiya P, Kaur Simerpreet, Bhardwaj R, Chaudhary K.Ellis-van Creveld syndrome: A rare clinical entity.J Oral Maxillofac Pathol. 2013 Jan-Apr; 17(1): 132–135

Latham RA. The pathogenesis of cleft palate associated with the Pierre Robin syndrome. An analysis of a seventeen-week human foetus. Br J Plast Surg. 1966; 19: 205 –14.

Leth Jensen B, Kreiborg S, Dahl E, Fogh-Andersen P. Cleft lip and palate in Denmark, 1976-1981: epidemiology, variability, and early somatic development. Cleft Palate. 1988; 25: 258–69.

Lorenz P, Prager B, Tellkamp H. Frontonasal dysplasia: Case report and review of the literature. Kinderarztl Prax. 1990;58:415–20.

Loeys BL, Chen J, Neptune ER. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005; 37: 275–281

Livia P, Sibele A, Andreia B, Hercilio J, Edgard G. Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and or palate in the Brazilian population.Med Oral Patol Oral Cir Bucal.2013;18(3):e414-20

Milerad J, Larson O, PhD D, Hagberg C, Ideberg M. associated malformations in infants with cleft lip and palate: a prospective, population-based study. Paediatrics. 1997;100:180–6.

Murray JC: Gene/environment causes of cleft lip and/or palate. Clin Genet 2002; 61: 248–256

Murray JC, Schutte BC: Cleft palate: players, pathways, and pursuits. J Clin Invest 2004; 113: 1676–1678.

Martelli-Junior H, Coletta RD, Miranda RT, Barros LM, Swerts MS, Bonan PR. Orofacial features of Treacher Collins syndrome. Med Oral Patol Oral Cir Bucal. 2009;14:E344–8.

Mossey P, Little J. Addressing the challenges of cleft lip and palate research in India. J Plast Surg. 2009;42:S9-S18

Murray JC, Wehby GL, Ferreira M, Costa R, Felix T, Padovani C, et al. Oral cleft prevention programme.BMC Pediatr.2012;12:184

Neville BW, Damm DD, Allen CM, Bonqoute JE. Text book of Oral and Maxillofacial Pathology. 3rd ed. Philadelphia pennyslavania: WB Saunders Elsevier; 2009. pp. 45–6.

Rajabian MH, Sherkat M. An Epidemiologic study of Oral Clefts in Iran: an analysis of 1669 cases. Cleft Palate Craniofac J. 2000;37:191–6.

Ruiz-Perez VL, Tompson SW, Blair HJ, Espinoza-Valdez C, Lapunzina P, Silva EO, et al. Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. Am J Hum Genet. 2003;72:728–32.

Richieri-Costa A, Guion-Almeida ML. The syndrome of frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies-phenotypic and aetiological considerations. Int J Med Sci. 2009;1:34–42.

Shprintzen RJ, Sigel-Sadewitz VL, Amato J, Goldberg RB. Anomalies associated with clefts lip, cleft palate, or both. Am J Med Gent. 1985;20:585–95

Sullivan WG. Cleft lip with or with out cleft palate in blacks: An analysis of 81 patients. Plast Reconstr Surg. 1989;84:406–8.

Schutte BC, Murray JC: The many faces and factors of orofacial clefts. Hum Mol Genet 1999; 8:1853–1859.

Stoll C, Alembik Y, Dott B, Roth MP. Associated malformations in cases with oral clefts. Cleft Palate Craniofac J. 2000;37:41–7.

Shilpy S, Nikhil M, Samir D. Ellis-van Creveld syndrome. J Indian Soc Pedo Prev Dent. 2007;25:S5–7

Sakai D, Trainor PA. Treacher Collins syndrome: Unmasking the role of Tcof1/treacle. Int J Biochem Cell Biol. 2009;41:1229–32.

Shete P, Tupkari JV, Benjamin T, Singh A. Treacher Collins Syndrome. J Oral Maxillofac Pathol. 2011 Sep-Dec; 15(3): 348–351.

Sharma S, Sharma V, Bothra M. Frontonasal dysplasia (Median cleft face syndrome). J Neurosci Rural Pract. 2012 Jan-Apr; 3(1): 65–67.

Tay MT, Quah BL. Mandibulo-Facial Dysostosis- The eye signs of a case study. Singapore Med J. 1991;32:365–7.

Tolorova MM, Cervenka J. Classification and birth prevalence of orofacial clefts. AM J med Genet. 1998;75:126–37.

Trainor PA, Dixon J, Dixon MJ. Treacher Collins syndrome: Etiology, pathogenesis and prevention. Eur J Hum Genet. 2009;17:275–83.

Taghavi N, Mollaian M, Alizadeh P, Moshref M, Modabernia, Akbarzadeh AR. Orofacial clefts and risk factors in Tehran, Iran: A case-control study. Iranian Red Crescent Medical Journal.2012;14(1):25-30

Van den Boogaard MJ, Dorland M, Beemer FA, van Amstel HK: MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans. Nat Genet 2000; 24: 342–343.

Venkatesh R.Syndromes and anomalies associated with cleft. Indian J Plast Surg. 2009 Oct; 42(Suppl): S51–S55.

Wong F K, Hagg U.An update on the aetiology of orofacial clefts.Hong Kong Med J.2004;10:331-6

Zhou QJ, Shi B, Shi ZD, Zheng Q, Wang Y. Survey of the patients with cleft lip or palate in China who were funded for the surgery by the Smile Train program from 2000-2002. Chin Med J (Engl) 2006; 119: 1695–700.


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