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. 2008 Feb 23;336(7641):432-4.
doi: 10.1136/bmj.39458.563611.AE. Epub 2008 Feb 4.

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

Ase Sivertsen  1 , Allen J Wilcox, Rolv Skjaerven, Hallvard Andreas Vindenes, Frank Abyholm, Emily Harville, Rolv Terje Lie
Affiliations

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

Ase Sivertsen et al. BMJ. .

Abstract

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

Design: Population based cohort study.

Setting: Data from the medical birth registry of Norway linked with clinical data on virtually all cleft patients treated in Norway over a 35 year period.

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

Main outcome measure: Relative risk of recurrence of isolated clefts from parent to child and between full siblings, for anatomic subgroups of clefts.

Results: Among first degree relatives, the relative risk of recurrence of cleft was 32 (95% confidence interval 24.6 to 40.3) for any cleft 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 affected fathers was similar. Risks of recurrence were also similar for parent-offspring and sibling-sibling pairs. The "crossover" risk between any cleft lip and cleft palate only was 3.0 (1.3 to 6.7). The severity of the primary case was unrelated to the risk of recurrence.

Conclusions: The stronger family recurrence of cleft palate only suggests a larger genetic component for cleft palate only than for any cleft lip. The weaker risk of crossover between the two types of cleft indicates relatively distinct causes. The similarity of mother-offspring, father-offspring, and sibling-sibling risks is consistent with genetic risk that works chiefly through fetal genes. Anatomical severity does not affect the recurrence risk in first degree relatives, which argues against a multifactorial threshold model of causation.

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Conflict of interest statement

Competing interests: None declared.

Figures

None
Fig 1 Follow-up through generations. *People without non-cleft birth defects; diagnosis of cleft was clinically verified. †Diagnosis of cleft was verified in medical birth registry, in clinical data, or in both; stillborn babies and people with non-cleft birth defects are included. ‡Overall marked lower proportion of men who have reproduced is because women tend to have children with men older than themselves (men born before 1967 and not included in study cohort)
None
Fig 2 Follow-up of babies who had at least one subsequent full sibling. *A woman’s first recorded baby; stillborn babies and babies with non-cleft birth defects are not included; diagnosis of cleft was verified in clinical data. †Number of mothers who had more than one baby (not plural births) with the same partner. ‡Stillborn babies and babies with non-cleft births defects are included; diagnosis of cleft was verified in medical birth registry, in clinical data, or in both
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Comment in

  • Familial risks of oral clefts.
    Lees M. Lees M. BMJ. 2008 Feb 23;336(7641):399. doi: 10.1136/bmj.39470.657685.80. Epub 2008 Feb 4. BMJ. 2008. PMID: 18250101 Free PMC article.

References

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