Congenital orofacial clefts: Etiology and Frequency

Öz

Orofacial clefts are congenital structural anomalies of the lip and/or palate. These anomalies affect ~1/1000 in the community. The etiology of orofacial clefts is complex, including various genetic and environmental agents. Syndrome is not accompanied by any isolated orofacial clefts are more common, although environmental factors often play a role in the etiology. Mendelian or teratogenic origins; the non-syndromic forms of orofacial clefts are more common and are likely due to secondary gene–environment interactions. Latest researches in both molecular and quantitative approaches have begun to identify the genes responsible for the rare syndromic forms of cleft and have also identified both candidate genes and loci for the more common and complex non-syndromic variants. Animal models, have also contributed greatly to an comprehension of these anomalies. We aimed to describes genes that are involved in orofacial clefts in humans and animal models and explores genetic approaches to identifying additional genes and gene–environment interactions that constitute the many factors of orofacial clefts in this review.

Anahtar Kelimeler

• Congenital anomalies, lip and palate cleft, orofacial cleft

Konjenital orofasiyal yarıklar: Etyolojisi ve sıklığı

Öz

Orofasial yarıklar toplumda ∼1/1000 oranında görülmekle birlikte damak ve dudakta beraber bazen de izole olarak görülmektedirler. Orofasial yarıkların etyolojisinde bir çok faktör rol almaktadır. Ayrıca etyolojisi multipl genetik ve çevresel faktörleri içermektedir. Bu patolojinin nadir formları mendeliyen ve teratojenik orijine sahip multipl konjenital anomaliye sahip sendromların bir komponenti olabilir. Herhangi bir sendromun eşlik etmediği izole orofasial yarıklar daha sık görülmekle birlikte etyolojide genelde çevresel faktörler rol oynamaktadır. Genetik biliminde moleküler ve kantitatif olarak meydana gelen gelişmeler bu patolojinin sendromik ve sendromik olmayan her iki tipinde de genetik mekanizmalarının rol oynuyor olabileceğini düşündürmektedir. Hayvan modellerinde yapılan çalışmalarda bu patolojinin etyolojisine ışık tutmaya çalışmaktadır. Biz bu derlememizle orofasial yarık içeren insan ve hayvan modellerinde genetik faktörleri değerlendirmek ve genetik ile çevresel faktörlerin birbiriyle ilişkisini belirlemeyi amaçladık.

Anahtar Kelimeler

• Konjenital anomaliler, dudak-damak yarığı, orofasiyal yarık

Kaynakça

1. Vanderas AP. Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review. Cleft Palate J 1987;24:216-25.
2. Hoşnuter M, Aktunç E, Kargı E, et al. Yarık damak dudak aile rehberi. Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi 2009;9:9-13
3. Romitti PA, Lidral AC, Munger RG, et al. Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: Evaluation of genotype- environment interactions from a population-based case- control study of orofacial clefts. Teratology 1999;59:39-50
4. Francis-West P, Ladher R, Barlow A, Graveson A. Signal- ling interactions during facial development. Mech Dev 1998;75:3–28
5. Fraser FC. The genetics of cleft lip and cleft palate. Am J Hum Genet 1970;22:336–352.
6. Jones MC. Etiology of facial clefts: prospective evaluation of 428 patients. Cleft Palate J 1988;25:16-20.
7. Brewer C, Holloway S, Zawalnyski P, et al. A chromosomal deletion map of human malformations. Am J Hum Genet 1998;63:1153–1159.
8. Fogh-Andersen P. Inheritance of Harelip and Cleft Palate. Munksgaard, Copenhagen, Denmark 1942.

9. Mitchell LE, Risch N. Mode of inheritance of nonsyndromic cleft lip with or without cleft palate: a reanalysis. Am J Hum Genet 1992;51:323-332.
10. Wyszynski DF, Beaty TH, Maestri NE. Genetics of non- syndromic oral cleft revizited. Cleft Palate Craniofac J 1996;33:406-417.
11. Eiberg H, Bixler D, Nielsen LS, et al. Suggestion of link- age of a major locus for nonsyndromic orofacial cleft with F13A and tentative assignment to chromosome 6. Clin. Genet 1987;32:129–132.
12. Thompson JS, Thompson MW. Genetics in medicine (3rd ed.) W.B. Saunders Company, Philadelphia, London, To- ronto 1980.
13. Ardinger HH, Buetow KH, Bell GI, et al. Association of ge- netic variation of the transforming growth factor-alpha gene with cleft lip and palate. Am J Hum Genet 1989;45:348– 353.
14. Mitchell LE, Healey SC, Chenevix-Trench G. Evidence for an association between nonsyndromic cleft lip with or without cleft palateand a gene located on the long arm of chromosome 4. Am J Hum Genet 1995;57:1130–1136.
15. Juriloff DM, Mah DG. The major locus for multifactorial nonsyndromic cleft lip maps to mouse chromosome 11. Mamm Genome 1995;6,:63–69.
16. Houzelstein D, Cohen A, Buckingham ME, et al. Insertional mutation of the mouse Msx1 homeobox gene by an nlacZ reporter gene. Mech Dev 1997;65:123–133.
17. Sun D, Vanderburg CR, Odierna GS, et al. TGFbeta3 pro- motes transformation of chicken palate medial edge epithe- lium to mesenchyme in vitro. Development 1998;125:95– 105.
18. Burdick AB, Bixler D, Puckett CL. Genetic analysis in fam- ilies with van der Woude syndrome. J Craniofac Genet Dev Biol 1985;5:181–208.
19. Wienker TF, Hudek G, Bissbort S, et al. Linkage studies in a pedigree with Van der Woude syndrome. J. Med. Genet 1987;24:160–162.
20. Bocian M, Walker AP. Lip pits and deletion 1q32–41. Am J Med Genet 1987;26:437–443.
21. Warkany J, Nelson RC, Schraffenberger E. Congenital mal- formations induced in rats by maternal nutritional deficien- cy. Am J Dis Child 1943;65:882–894.
22. Cembrano JRJ, d Vera JS, Joaquino JB, et al. Familial risk of recurrence of clefts of the lip and palate. Philipp J Surg Surg Spec 1995;50:37–40.
23. Shaw GM, Wasserman CR, Murray JC, et al. Infant TGF-alpha genotype, orofacial clefts, and maternal peri- conceptional multivitamin use. Cleft Palate Craniofac J 1998;35:366–370.
24. Christensen K, Olsen J, Norgaard-Pedersen B, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population based case–control study in Denmark, 1991–1994. Am J Epidemiol 1999;149:248–255.
25. Romitti PA, Lidral AC, Munger RG, et al. Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: Evaluation of genotype–environment interactions from a population- based case–control study of orofacial clefts. Teratology 1999;59:39–50.
26. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embri- opathy. N Engl J Med 1985;313:837–841.
27. Tolarova M, Harris J. 1995 Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins. Teratology 1995;51:71–78.
28. Jacobsson C, Granstrom G. Effects of vitamin B6 on beta- aminoproprionitrile-induced palatal cleft formation in the rat. Cleft Palate Craniofac J 1997;34:95–100.