Incidence patterns of orofacial clefts in purebred dogs

Autoři: Nicholas Roman aff001;  Patrick C. Carney aff002;  Nadine Fiani aff002;  Santiago Peralta aff002
Působiště autorů: College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America aff001;  Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224574


Cleft lip (CL), cleft palate (CP) and cleft lip and palate (CLP) are the most common types of orofacial clefts in dogs. Orofacial clefts in dogs are clinically relevant because of the associated morbidity and high newborn mortality rate and are of interest as comparative models of disease. However, the incidence of CL, CP and CLP has not been investigated in purebred dogs, and the financial impact on breeders is unknown. The aims of this study were to document the incidence patterns of CL, CP and CLP in different breeds of dogs, determine whether defect phenotype is associated with skull type, genetic cluster and geographic location, and estimate the financial impact in breeding programs in the United States by means of an anonymous online survey. A total of 228 orofacial clefts were reported among 7,429 puppies whelped in the 12 preceding months. Breeds in the mastiff/terrier genetic cluster and brachycephalic breeds were predisposed to orofacial clefts. Certain breeds in the ancient genetic cluster were at increased odds of orofacial clefts. Male purebred dogs were at increased odds of CPs. Results confirm that brachycephalic breeds are overrepresented among cases of orofacial clefts. Furthermore, geographic region appeared to be a relevant risk factor and orofacial clefts represented a considerable financial loss to breeders. Improved understanding of the epidemiology of orofacial clefts (frequency, causes, predictors and risk factors) may help in identifying ways to minimize their occurrence. Information gained may potentially help veterinarians and researchers to diagnose, treat and prevent orofacial clefts.

Klíčová slova:

Cleft lip and palate – Cleft palate – Dogs – Finance – Paleogenetics – Pets and companion animals – Surveys


1. Fiani N, Verstraete FJM, Arzi B. Reconstruction of congenital nose, cleft primary palate, and lip disorders. Vet Clin North Am Small Anim Pract. 2016;46(4):663–75. doi: 10.1016/j.cvsm.2016.02.001 26965528.

2. Moura E, Pimpão CT. Cleft lip and palate in the dog: medical and genetic aspects. In: Almasri MA, editor. Designing Strategies for Cleft Lip and Palate Care. Rijeka: InTech; 2017. p. Ch. 08.

3. Indrebø A, Trangerud C, Moe L. Canine neonatal mortality in four large breeds. Acta Vet Scand. 2007;49(1):S2. doi: 10.1186/1751-0147-49-s1-s2

4. Kemp C, Thiele H, Dankof A, Schmidt G, Lauster C, Fernahl G, et al. Cleft lip and/or palate with monogenic autosomal recessive transmission in Pyrenees shepherd dogs. Cleft Palate Craniofac J. 2009;46(1):81–8. Epub 2009/01/01. doi: 10.1597/06-229.1 19115787.

5. Nemec A, Daniaux L, Johnson E, Peralta S, Verstraete FJ. Craniomaxillofacial abnormalities in dogs with congenital palatal defects: computed tomographic findings. Vet Surg. 2015;44(4):417–22. doi: 10.1111/j.1532-950X.2014.12129.x 24433432.

6. Wolf ZT, Leslie EJ, Arzi B, Jayashankar K, Karmi N, Jia Z, et al. A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLoS Genet. 2014;10(4):e1004257. doi: 10.1371/journal.pgen.1004257 24699068; PubMed Central PMCID: PMC3974639.

7. Martinez-Alvarez C, Gonzalez-Meli B, Berenguer-Froehner B, Paradas-Lara I, Lopez-Gordillo Y, Rodriguez-Bobada C, et al. Injection and adhesion palatoplasty: a preliminary study in a canine model. J Surg Res. 2013;183(2):654–62. Epub 2013/04/02. doi: 10.1016/j.jss.2013.03.009 23541812.

8. Paradas-Lara I, Casado-Gomez I, Martin C, Martinez-Sanz E, Lopez-Gordillo Y, Gonzalez P, et al. Maxillary growth in a congenital cleft palate canine model for surgical research. J Craniomaxillofac Surg. 2014;42(1):13–21. Epub 2013/02/26. doi: 10.1016/j.jcms.2013.01.032 23434237.

9. Lobodzinska A, Gruszczynska J, Max A, Bartyzel BJ, Mikula M, Mikula I Jr, et al. Cleft palate in the domestic dog, Canis lupus familiaris–etiology, pathophysiology, diagnosis, prevention, and treatment. Acta Scientiarum Polonorum Zootechnica. 2014;13(3).

10. Peralta S, Nemec A, Fiani N, Verstraete FJ. Staged double-layer closure of palatal defects in 6 dogs. Vet Surg. 2015;44(4):423–31. Epub 2014/01/31. doi: 10.1111/j.1532-950X.2014.12131.x 24476120.

11. Peralta S, Campbell RD, Fiani N, Kan-Rohrer KH, Verstraete FJM. Outcomes of surgical repair of congenital palatal defects in dogs. J Am Vet Med Assoc. 2018;253(11):1445–51. Epub 2018/11/20. doi: 10.2460/javma.253.11.1445 30451614.

12. Peralta S, Fiani N, Kan-Rohrer KH, Verstraete FJM. Morphological evaluation of clefts of the lip, palate, or both in dogs. Am J Vet Res. 2017;78(8):926–33. doi: 10.2460/ajvr.78.8.926 28738009.

13. Calnan J. The comparative anatomy of cleft lip and palate. I. Classification of cleft lip and palate in dogs. Br J Plast Surg. 1961;14:180–4. Epub 1961/10/01. doi: 10.1016/s0007-1226(61)80033-7 13875838.

14. Mulvihill JJ, Mulvihill CG, Priester WA. Cleft palate in domestic animals: epidemiologic features. Teratology. 1980;21(1):109–12. doi: 10.1002/tera.1420210115 7385051.

15. Warzee CC, Bellah JR, Richards D. Congenital unilateral cleft of the soft palate in six dogs. J Small Anim Pract. 2001;42(7):338–40. Epub 2001/08/02. doi: 10.1111/j.1748-5827.2001.tb02469.x 11480899.

16. White R, Hawkins H, Alemi V, Warner C. Soft palate hypoplasia and concurrent middle ear pathology in six dogs. J Small Anim Pract. 2009;50(7):364–72. doi: 10.1111/j.1748-5827.2009.00742.x 19575700

17. Villagomez DA, Alonso RA. A distinct Mendelian autosomal recessive syndrome involving the association of anotia, palate agenesis, bifid tongue, and polydactyly in the dog. Can Vet J. 1998;39(10):642–3. Epub 1998/10/28. 9789676; PubMed Central PMCID: PMC1539452.

18. Jurkiewicz M, Bryant D. Cleft lip and palate in dogs: a progress report. Cleft Palate J. 1968;5(1):30–6.

19. Van Den Berghe F, Cornillie P, Stegen L, Van Goethem B, Simoens P. Palatoschisis in the dog: developmental mechanisms and etiology. Vlaams Diergeneeskundig Tijdschrift. 2010;79(2):117–23.

20. Khandelwal KD, van Bokhoven H, Roscioli T, Carels CE, Zhou H. Genomic approaches for studying craniofacial disorders. Am J Med Genet C Semin Med Genet. 2013;163C(4):218–31. doi: 10.1002/ajmg.c.31379 24142857.

21. Wolf ZT, Brand HA, Shaffer JR, Leslie EJ, Arzi B, Willet CE, et al. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate. PLoS Genet. 2015;11(3):e1005059. doi: 10.1371/journal.pgen.1005059 25798845; PubMed Central PMCID: PMC4370697.

22. Moura E, Cirio SM, Pimpao CT. Nonsyndromic cleft lip and palate in boxer dogs: evidence of monogenic autosomal recessive inheritance. Cleft Palate Craniofac J. 2012;49(6):759–60. Epub 2011/08/03. doi: 10.1597/11-110 21806339.

23. Richtsmeier JT, Sack GH Jr., Grausz HM, Cork LC. Cleft palate with autosomal recessive transmission in Brittany Spaniels. Cleft Palate Craniofac J. 1994;31(5):364–71. Epub 1994/09/01. doi: 10.1597/1545-1569_1994_031_0364_cpwart_2.3.co_2 7986797.

24. vonHoldt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, et al. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. 2010;464:898. doi: 10.1038/nature08837 20237475

25. Parker HG. Genomic analyses of modern dog breeds. Mamm Genome. 2012;23(1–2):19–27. Epub 2012/01/11. doi: 10.1007/s00335-011-9387-6 22231497; PubMed Central PMCID: PMC3559126.

26. Elwood JM, Colquhoun TA. Observations on the prevention of cleft palate in dogs by folic acid and potential relevance to humans. N Z Vet J. 1997;45(6):254–6. Epub 2005/07/21. doi: 10.1080/00480169.1997.36041 16032001.

27. Davies M. Excess vitamin A intake during pregnancy as a possible cause of congenital cleft palate in puppies and kittens. Vet Rec. 2011;169(4):107. doi: 10.1136/vr.d4614 21784811.

28. Richman WL, Kiesler S, Weisband S, Drasgow F. A meta-analytic study of social desirability distortion in computer-administered questionnaires, traditional questionnaires, and interviews. J Appl Psychol. 1999;84(5):754–75. doi: 10.1037/0021-9010.84.5.754 WOS:000083816600009.

29. Auger M, Alexander K, Beauchamp G, Dunn M. Use of CT to evaluate and compare intranasal features in brachycephalic and normocephalic dogs. J Small Anim Pract. 2016;57(10):529–36. doi: 10.1111/jsap.12541 27508338

30. Teng KT, McGreevy PD, Toribio J-ALML, Dhand NK. Trends in popularity of some morphological traits of purebred dogs in Australia. Canine Genet Epidemiol. 2016;3(1):2. doi: 10.1186/s40575-016-0032-2 27051522

31. Evans HE, de Lahunta A. Miller's Anatomy of the Dog. Philadelphia: Elsevier Health Sciences; 2013. Available from:

32. Selba MC, Oechtering GU, Heng HG, DeLeon VB. The impact of selection for facial reduction in dogs: geometric morphometric analysis of canine cranial shape. Anat Rec (Hoboken). 2019. Epub 2019/06/04. doi: 10.1002/ar.24184 31152493.

33. Roberts T, McGreevy P, Valenzuela M. Human induced rotation and reorganization of the brain of domestic dogs. PLoS One. 2010;5(7):e11946. Epub 2010/07/30. doi: 10.1371/journal.pone.0011946 20668685; PubMed Central PMCID: PMC2909913.

34. Meola SD. Brachycephalic airway syndrome. Top Companion Anim Med. 2013;28(3):91–6. Epub 2013/11/05. doi: 10.1053/j.tcam.2013.06.004 24182996.

35. Natsume N, Miyajima K, Kinoshita H, Kawai T. Incidence of cleft lip and palate in Beagles. Plast Reconstr Surg. 1994;93(2):439. doi: 10.1097/00006534-199402000-00042 8310041.

36. Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet. 2009;374(9703):1773–85. Epub 2009/09/15. doi: 10.1016/S0140-6736(09)60695-4 19747722.

37. Watkins SE, Meyer RE, Strauss RP, Aylsworth AS. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014;41(2):149–63. Epub 2014/03/13. doi: 10.1016/j.cps.2013.12.003 24607185.

38. Gundlach KK, Maus C. Epidemiological studies on the frequency of clefts in Europe and world-wide. J Craniomaxillofac Surg. 2006;34 Suppl 2:1–2. Epub 2006/10/31. doi: 10.1016/s1010-5182(06)60001-2 17071381.

39. Derijcke A, Eerens A, Carels C. The incidence of oral clefts: a review. Br J Oral Maxillofac Surg. 1996;34(6):488–94. Epub 1996/12/01. doi: 10.1016/s0266-4356(96)90242-9 8971440.

40. Shapira Y, Lubit E, Kuftinec MM, Borell G. The distribution of clefts of the primary and secondary palates by sex, type, and location. Angle Orthod. 1999;69(6):523–8. Epub 1999/12/11. doi: 10.1043/0003-3219(1999)069<0523:TDOCOT>2.3.CO;2 10593442.

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2019 Číslo 11