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

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 parentoffspring 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, fatheroffspring, 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.

GJA1mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype

“…Tables S4 and S5). One facial feature observed, cleft palate (CP), was seen in six unrelated ODDD individuals (3% of 177 ODDD individuals as compared to 0.05% in the general population [Sivertsen et al, 2008]). There may be clustering of Cx43 mutations associated with this feature as three of these sporadic cases have mutations (L7V, L11P, and G22E) occurring in or adjacent to the amino terminal domain, but there are different mutations in this same region (Y17S, S18P, G2V, L7V, and G21R) in each of the five families with 11 affected members that do not have CP.…”

Epidemiological Study of Cleft Palate in the State of Bahia, Brazil

“…The familial recurrence of NSCP is common in the literature and it is closely related to the genetic base of cleft palate, which is not completely clarified yet 25 . Our results showed that 28.1% of the subjects had a family history of cleft palate.…”

Cleft lip and cleft palate: a disease with multiple risk factors in a pregnant woman

“…5 Evidence also shows that the risk of oral clefts among first degree relatives of cases is much higher than that in the general population. 6 Risk factors such as maternal smoking, maternal age, alcohol consumption, gender, medicinal drugs, viral infection and exposure to teratogens during early pregnancy have previously been investigated. [1][2][3][4][5][6][7] Researchers have proposed some other theories to explain the origin of CLP.…”

“…6 Risk factors such as maternal smoking, maternal age, alcohol consumption, gender, medicinal drugs, viral infection and exposure to teratogens during early pregnancy have previously been investigated. [1][2][3][4][5][6][7] Researchers have proposed some other theories to explain the origin of CLP. Other associated factors are the antiepileptic drugs usage, maternal (toxoplasmosis, rubella, cytomegalovirus, herpes simplex TORCH) infections, nutritional deficiencies (especially folic acid) during pregnancy, and consanguineous marriage between the parents.…”