Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

doi:10.1136/bmj.39458.563611.AE

BMJ 2008;336:432-434 (23 February), doi:10.1136/bmj.39458.563611.AE (published 4 February 2008)

Research

Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

Åse Sivertsen, consultant plastic surgeon¹^,2, Allen J Wilcox, senior investigator³, Rolv Skjærven, professor², Hallvard Andreas Vindenes, consultant plastic surgeon¹, Frank Åbyholm, professor⁴, Emily Harville, assistant professor⁵, Rolv Terje Lie, professor²

¹ Department of Plastic Surgery, Haukeland University Hospital, No-5021 Bergen, Norway, ² Department of Public Health and Primary Health Care, University of Bergen, Kalfarveien 1, N-5018 Bergen, ³ Epidemiology branch, National Institute of Environmental Health Sciences, NIH, Durham, NC 27709, USA, ⁴ Department of Plastic Surgery, Rikshospitalet, N-0027 Oslo, Norway, ⁵ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA

Correspondence to: Å Sivertsen ase.sivertsen{at}isf.uib.no

Objective To estimate the relative risk of recurrence of oralcleft in first degree relatives in relation to cleft morphology.

Design Population based cohort study.

Setting Data from the medical birth registry of Norway linkedwith clinical data on virtually all cleft patients treated inNorway over a 35 year period.

Participants 2.1 million children born in Norway between 1967and 2001, 4138 of whom were treated for an oral cleft.

Main outcome measure Relative risk of recurrence of isolatedclefts from parent to child and between full siblings, for anatomicsubgroups of clefts.

Results Among first degree relatives, the relative risk of recurrenceof cleft was 32 (95% confidence interval 24.6 to 40.3) for anycleft lip and 56 (37.2 to 84.8) for cleft palate only (P difference=0.02).The risk of clefts among children of affected mothers and affectedfathers was similar. Risks of recurrence were also similar forparent-offspring and sibling-sibling pairs. The "crossover"risk between any cleft lip and cleft palate only was 3.0 (1.3to 6.7). The severity of the primary case was unrelated to therisk of recurrence.

Conclusions The stronger family recurrence of cleft palate onlysuggests a larger genetic component for cleft palate only thanfor any cleft lip. The weaker risk of crossover between thetwo types of cleft indicates relatively distinct causes. Thesimilarity of mother-offspring, father-offspring, and sibling-siblingrisks is consistent with genetic risk that works chiefly throughfetal genes. Anatomical severity does not affect the recurrencerisk in first degree relatives, which argues against a multifactorialthreshold model of causation.

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