In general, we believe that environmental factors and genetic factors are the two factors that play a key role in the development of congenital malformations. Environmental factors account for about 10%, genetic factors for about 25%, and environmental factors interacting with genetic factors and unknown causes for about 65% of cases.
Some patients with cleft lip and palate can be found to have similar deformities in their immediate or collateral relatives, so it is believed that there is a genetic relationship between cleft lip and palate. Genetic studies have concluded that cleft lip and palate is a polygenic genetic disorder. It has been reported in the literature that 27% of cleft lip and palate are from genetic origin and that there is a distinction between dominant and recessive inheritance, but it may not be passed from generation to generation.
In fact, the heritability of cleft lip and palate cannot be generalized, and cleft lip and palate is divided into two categories: syndromic and non-syndromic. Non-syndromic cleft lip and palate is a single cleft lip, cleft palate, or cleft lip combined with cleft palate, accounting for more than 70% of the total facial cleft deformities, which excludes other systemic deformities and syndromic cleft lip and palate. The heritability of non-syndromic cleft lip and palate is very low. Syndromic cleft lip and palate refers to cleft lip, cleft palate, or cleft lip and palate with other systemic anomalies, mostly with family history, such as Robin’s sequence (cleft palate with small jaw deformity).
The heritability of syndromic cleft lip and palate is relatively high, and clinical statistics show that the closer the kinship, the higher the prevalence. The prevalence of cleft lip and cleft palate is higher in males than in females, and children of male patients usually have cleft lip only, but children of female patients are more likely to have both cleft lip and cleft palate.
Children born with a family history of cleft lip and palate may have a slightly higher rate of cleft lip and palate, with some data reporting that the incidence of children born to parents with cleft lip can be as high as 2.6-5.6%.
The human genetic material is carried mainly by chromosomes in cells. There are 23 pairs of chromosomes, one of which determines sex, called sex chromosomes, and the remaining 22 pairs are autosomes. If a chromosome carries a gene that expresses its characteristics, it is called dominant inheritance, while the opposite is recessive inheritance. A fetus receives one chromosome from each parent, and a deformity occurs when both are recessive genes.
Cleft lip is an autosomal recessive inheritance, it does not show malformations in every generation, only if both its parents who are healthy in appearance carry the gene that causes the disease, then 1/4 of their children will develop cleft lip, 1/2 of their children are apparently healthy but actually carry the gene that causes the disease and only 1/4 of their children are healthy.
(1) If both parents are normal, the probability of having the first child with a cleft lip and palate is 1/550; (2) If both parents are normal and one child has a cleft lip and palate, the probability of having the second child with a cleft lip and palate is 1/20; (3) If both parents are normal and the first and second children have a cleft lip and palate, the probability of having the third child with a cleft lip and palate is 1/25. (4) If one parent has a cleft lip and palate, the probability of having a child with a cleft lip and palate is 1/25; (5) If one parent has a cleft lip and palate and one child has a cleft lip and palate, the probability of having a second child with a cleft lip and palate is 1/25; (6) If both parents have a cleft lip and palate, the probability of having the first child with a cleft lip and palate is 1/25. This data should be used as a reference only.