Recurrence risk for offspring of twins discordant for oral cleft: a population-based cohort study of the Danish 1936-2004 cleft twin cohort.
Our objective in this Danish population-based cohort study was to estimate the recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co-twins of OC discordant twin pairs and to compare this risk to the recurrence risk in the offspring of the affected co-twin as well as to the risk in the background population. During 1936-2004, 207 twin pairs were ascertained, among whom at least one twin had an OC. The index persons were twins discordant for OC who had children (N=117), and their offspring (N=239). The participants were ascertained by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and The Danish Civil Registration System. In the study OC recurrence risk for offspring of the affected and unaffected twin and relative risk were compared to the background prevalence. We found that among 110 children of the 54 OC affected twins, two (1.8%) children had OC corresponding to a significantly increased relative risk (RR=10; 95% CI 1.2-35) when compared to the frequency in the background population. Among the 129 children of the 63 unaffected twins, three (2.3%) children were affected, corresponding to a significantly increased relative risk (RR=13; 95% CI 2.6-36) when compared the background prevalence. We concluded that in OC discordant twin pairs similar increased recurrence risks were found among offspring of both OC affected and OC unaffected twins. This provides further evidence for a genetic component in cleft etiology and is useful information for genetic counseling of twin pairs discordant for clefting.
Grosen
Dorthe
D
Department of Epidemiology, University of Southern Denmark, Odense, Denmark. dgrosen@health.sdu.dk
Bille
Camilla
C
Pedersen
Jacob Krabbe
JK
Skytthe
Axel
A
Murray
Jeffrey C
JC
Christensen
Kaare
K
D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D030541:Databases, Genetic; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D012008:Recurrence; D012042:Registries; D012306:Risk; D018570:Risk Assessment; D035781:Siblings; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics
Epidemiology. 2005 May;16(3):311-6
15824545
Clin Genet. 2002 Apr;61(4):248-56
12030886
Am J Med Genet. 2002 Jun 15;110(2):182-3
12116259
Am J Med Genet. 1997 Oct 3;72(1):120-1
9295089
Cleft Palate Craniofac J. 1999 Mar;36(2):96-104
10213053
Cleft Palate Craniofac J. 2004 Nov;41(6):613-21
15516164
Twin Res Hum Genet. 2009 Oct;12(5):462-8
19803774
Orthod Craniofac Res. 2006 Feb;9(1):18-30
16420271
Orthod Craniofac Res. 2007 May;10(2):82-7
17552944
Am J Med Genet A. 2008 Jul 1;146A(13):1670-5
18536047
J Dent Res. 2008 Feb;87(2):119-25
18218836
Am J Med Genet. 1993 Nov 1;47(6):910-6
8279491
Cleft Palate Craniofac J. 1993 Sep;30(5):469-74
8218310
Am J Epidemiol. 2005 Jun 1;161(11):1047-55
15901625
Nat Genet. 2002 Oct;32(2):285-9
12219090
Cleft Palate Craniofac J. 1996 Jul;33(4):340-7
8827393
Cleft Palate Craniofac J. 2005 May;42(3):255-9
15865458
Twin Res. 2003 Aug;6(4):275-8
14511432
Am J Med Genet. 1996 Feb 2;61(4):371-6
8834050
J Med Genet. 2010 Mar;47(3):162-8
19752161
Twin Res Hum Genet. 2005 Feb;8(1):39-46
15836809
Am J Med Genet A. 2007 Dec 15;143A(24):3267-72
18000982
Twin Res. 2002 Oct;5(5):352-7
12537858
Am J Med Genet. 1996 Dec 30;66(4):468-70
8989470
Am J Med Genet A. 2007 Jun 1;143A(11):1143-9
17497721
J Craniofac Genet Dev Biol. 1996 Oct-Dec;16(4):234-41
8897213
Acta Genet Med Gemellol (Roma). 1989;38(3-4):305-13
2698574
Am J Med Genet A. 2008 Feb 15;146A(4):409-20
18203157
Ann Hum Genet. 1979 May;42(4):507-12
475337
Cleft Palate Craniofac J. 1996 Nov;33(6):530
8939382
Am J Hum Genet. 1996 Jan;58(1):182-90
8554055
Am J Hum Genet. 1992 Sep;51(3):654-9
1496993
Nat Genet. 1999 Mar;21(3):271-7
10080178