A cleft lip or palate results from a combination of a gene mutation and exposure to environmental factors that cause inflammation during pregnancy.
A study published in the peer-reviewed journal Nature Communications showed for the first time that both genetic and environmental factors, such as smoking or infections, play a role in forming a cleft lip or palate in a developing fetus.
Cleft lip, with or without cleft palate, affects one in 700 live births and is the most common craniofacial malformation seen at birth. It occurs if the tissue that makes up the lip does not join completely before birth, resulting in an opening in the upper lip, whereas a cleft palate happens when the tissue that makes up the roof of the mouth does not join together completely.
The malformation may cause difficulty feeding, speaking, and hearing. Moreover, people with cleft lip or palate are at a higher risk for ear infections and dental problems.
It has been previously thought mutations in the E-cadherin gene may be involved in developing cleft lip. However, when the researchers from the University College London and the University of São Paulo studied families carrying these mutations, they found that not everyone with the mutation develops a cleft lip.
The researchers then reproduced the e-cadherin gene mutation in mice and frogs. The animals developed malformations similar to the cleft lip in humans, but only when the mice and frogs carrying the mutation were also exposed to environmental factors that cause inflammation. The researchers also found similar effects in human stem cells with both mutation and inflammation.
According to the study, diabetes, maternal infections, and obesity are potential common causes of pro-inflammatory conditions during pregnancy that are associated with cleft lip.
Previous research suggested that women diagnosed with diabetes before pregnancy are at a higher risk of having a child with a cleft lip compared to women who do not have diabetes. The use of certain epilepsy medicines, such as topiramate or valproic acid, during the first trimester, has also been associated with an elevated risk of giving birth to a baby with a cleft lip.
Surgery is the only way to repair a cleft lip or palate. It improves the appearance of a face and can help with breathing, hearing, speech, and language development. Surgical repair for a cleft lip is recommended within the first 12 months of life, while surgery to repair a cleft palate should be performed before a child turns 18 months old.
The authors hope that their findings will help to develop new treatments or preventative strategies for cleft lip or palate. For example, if screening for the E-cadherin gene was a part of antenatal care, those carrying the mutation could be advised to target risk factors or be prescribed anti-inflammatory drugs.