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Risk of Oral Clefts in Twins

Grosen, Dorthea; Bille, Camillaa; Petersen, Ingea; Skytthe, Axela; Hjelmborg, Jacob von Bornemannb; Pedersen, Jacob Krabbea; Murray, Jeffrey Clarka,c; Christensen, Kaarea,d

doi: 10.1097/EDE.0b013e3182125f9c
Reproduction: Original Article

Background: Small studies have indicated that twinning increases the risk of oral cleft.

Methods: We used data from a Danish national population-based cohort study to investigate whether twinning was associated with isolated oral cleft, and to estimate the twin probandwise concordance rate and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion ratio for twins versus singletons, stratified for 3 subphenotypes. Probandwise concordance rates and heritability for twins were estimated for 2 phenotypes—cleft lip with or without cleft palate (CL/P) and cleft palate (CP).

Results: The prevalence of oral cleft was 15.8 per 10,000 twins and 16.6 per 10,000 singletons (prevalence proportion ratio = 0.95; 95% confidence interval = 0.83–1.1). This prevalence was similar for monozygotic and dizygotic twins. The probandwise concordance rate was higher for CL/P for monozygotic twins than for dizygotic twins (50% vs. 8%, respectively). A similar contrast was present for CP. Recurrence risk for both types of clefts was greater in dizygotic twins than in non-twin siblings. Heritability estimates were above 90% for both CL/P and CP.

Conclusions: No excess risk of oral cleft could be demonstrated for twins compared with singletons. The concordance rates and heritability estimates for both types of clefts show a strong genetic component.


From the Departments of aEpidemiology and bStatistics, Institute of Public Health, University of Southern Denmark, Odense, Denmark; cDepartment of Pediatrics, University of Iowa, Iowa City, IA; and dDepartments of Biochemistry and Pharmacology and of Clinical Genetics, Odense University Hospital, Odense, Denmark.

Submitted 30 June 2010; accepted 9 November 2010.

Supported by University of Southern Denmark, Danish Graduate School in Public Health; and NIH (grant numbers R01 DE-11948 and DE-08559).

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Correspondence: Dorthe Grosen, Department of Epidemiology, Institute of Public Health, University of Southern Denmark, J. B. Winsløws Vej 9B, DK-5000 Odense C, Denmark. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.