From The Bench with Francis: Recent Developments in Cleft Lip and Palate Dental Research

By Francis Smith

I just found a newly released article in the Journal of Dental Research that links dental problems associated with cleft lip and palate to abnormalities in salivary glands and an imbalance of immune compounds in the mouth.

In his article, "Massively Increased Caries Susceptibility in an Irf6 Cleft Lip/Palate Model" in the Dec. 7, 2016, issue of the Journal of Dental Research, Dr. Timothy Cox (a researcher at Seattle Children's Research Institute affiliated with Seattle Children's Hospital and the University of Washington) found that dental problems (such as high risk for dental caries) commonly associated with cleft lip and palate are linked to abnormalities in the salivary glands. Dr. Cox found that mice with a mutation in the gene Irf6, involved in the formation of the lips and palate, not only had cleft lip and palate, but that the gene mutation also resulted in abnormal formation of salivary glands (as opposed to mice in a control group, with no Irf6 mutation).

Dr. Cox and his team knocked out this major gene in a group of mice during late embryonic development in the oral epithelium (the outermost layer of tissue in the mouth). Mice with this Irf6 knockout had poorly formed salivary glands, leading to reduction in salivary flow rate and buffering capability, while significantly increasing the acidity of the oral environment. Also, Irf6 knockout mice had reduced expression of a major immune cytokine in their mucosal and skin tissues, leading to increased oral bacterial colonization. Increased bacterial colonization, along with a highly acidic environment in the mouth, combine to cause dental caries. Mice with this knockout condition displayed increased susceptibility to dental caries as a result of the salivary gland abnormalities, leading to high acidity and increased bacterial content in their mouths that worked to erode their teeth. A high sugar diet made this problem even worse. From this work, Dr. Cox concluded that individuals with cleft lip and palate are more susceptible to dental caries due to genetically linked salivary gland malformations that compromise salivary function and immune response against oral bacteria, leading to the high acidity and bacterial content that are involved in dental decay. Due to their susceptibility to dental caries, the oral and dental health of people with cleft lip and palate should be closely monitored and preventative measures taken early on in life to reduce this risk.