Genetic code forming a child's face, symbolizing genetic influence on orofacial development.

Cracking the Code: How Your Genes Influence Cleft Lip and Palate Risk

Lena Kashyap in Health & Wellness August 2025 • 4 min read.

"Unlocking the genetic secrets behind non-syndromic orofacial clefts may lead to better understanding and preventative strategies."

Orofacial clefts, characterized by the incomplete fusion of facial structures during development, are among the most common congenital abnormalities. While various factors contribute to their occurrence, genetics play a significant role, particularly in non-syndromic orofacial clefts (NSOC), which occur without other major developmental abnormalities.

Among all the risk factors during NSOC progression, the genetic factor takes a critical role. There are three main types of orofacial clefts: cleft lip only (CLO), cleft lip with palate (CLP), and cleft palate only (CPO) (Lacheretz and Poupard, 1972).

MicroRNAs (miRNAs), small non-coding RNA molecules, regulate gene expression and play crucial roles in craniofacial development. Expression and synthesis of miRNAs are regulated by miRNA processing genes. Disruptions in these regulatory processes can significantly impact embryonic development and increase the risk of clefts. Understanding these genetic underpinnings is essential for identifying potential preventative measures and therapeutic targets.

miRNA Processing Genes: What Role Do They Play in Cleft Lip/Palate?

Genetic code forming a child's face, symbolizing genetic influence on orofacial development.

A recent study explored the relationship between genetic variations in microRNA (miRNA) processing genes and the risk of non-syndromic orofacial clefts (NSOC). Researchers focused on single nucleotide polymorphisms (SNPs) within these genes to determine their potential impact on craniofacial development. The study looked at 12 potentially functional SNPs from seven miRNA processing genes (GEMIN3, DROSHA, DGCR8, GEMIN4, PIWIL1, XPO5, and DICER) in a case-control study of 602 NSOC cases and 605 controls.

The findings indicated a significant association between specific SNPs in the DROSHA gene and the susceptibility to cleft lip with or without palate (CL/P). Furthermore, these SNPs seemed to influence the risk differently depending on the specific genetic variation and its combination with other SNPs.

rs10719 in DROSHA: This SNP was found to increase the risk of CL/P. Specifically, individuals with the GA/AA genotype had a higher likelihood of developing cleft lip with or without palate (P=0.024, OR=1.33, 95% CI=[1.04, 1.70]). Similarly, those with the GG+GA/AA genotype also showed an increased risk (P=0.037, OR=1.29, 95% CI=[1.02, 1.63]).
rs493760 in DROSHA: Conversely, this SNP appeared to reduce the risk of CL/P. Individuals with the CC/TT genotype had a lower risk compared to others (P=0.049, OR=0.58, 95% CI=[0.34, 0.99]).
Haplotype Analysis: Researchers also examined how combinations of these SNPs (haplotypes) influenced risk. The rs10719 (A)-rs493760 (C) haplotype was associated with a decreased risk of CL/P (OR=0.77, 95% CI=[0.63, 0.94]). However, the rs10719 (G)-rs493760 (C) haplotype was linked to an increased risk of cleft palate only (CPO) (OR=2.70, 95% CI=[1.15, 6.35]).

While these results suggest a potential link between DROSHA gene variants and orofacial clefts, it’s important to note that the observed associations did not remain significant after Bonferroni correction, a statistical adjustment used to reduce the risk of false positives in multiple comparisons. Also, the other identified genes show no significant correlations.

Implications and Future Directions

This study provides preliminary evidence that variations in the DROSHA gene, specifically rs10719 and rs493760, may contribute to the risk of non-syndromic orofacial clefts. While further research is needed to confirm these findings and explore the underlying mechanisms, this work highlights the importance of miRNA processing genes in craniofacial development. Future studies with larger sample sizes and functional experiments are essential to validate these associations and identify potential therapeutic targets for preventing or treating orofacial clefts.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

What are the main types of orofacial clefts and how are they different?

The main types of orofacial clefts are cleft lip only (CLO), cleft lip with palate (CLP), and cleft palate only (CPO). These classifications indicate the specific facial structures affected during incomplete fusion during development. CLO involves only the lip, CLP affects both the lip and palate, while CPO exclusively involves the palate. These distinctions are crucial as they help in understanding the severity and specific genetic influences involved, as well as guiding treatment strategies.

What role do microRNAs (miRNAs) and miRNA processing genes play in the development of cleft lip and palate?

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression, making them essential for craniofacial development. miRNA processing genes regulate the expression and synthesis of miRNAs. Disruptions in these genes, such as single nucleotide polymorphisms (SNPs), can significantly impact embryonic development and potentially increase the risk of orofacial clefts. Variations within genes like DROSHA, which is involved in miRNA processing, have been associated with an increased risk of cleft lip with or without palate (CL/P). Understanding these processes is key for identifying potential preventative measures and therapeutic targets.

How does the DROSHA gene influence the risk of cleft lip and palate?

The DROSHA gene, a miRNA processing gene, has been linked to the risk of non-syndromic orofacial clefts (NSOC). Specific single nucleotide polymorphisms (SNPs) within DROSHA, such as rs10719 and rs493760, showed associations with the risk of cleft lip with or without palate (CL/P). Individuals with the GA/AA genotype of rs10719 showed an increased risk, while those with the CC/TT genotype of rs493760 had a reduced risk. Furthermore, haplotype analysis, which considers the combination of SNPs, revealed that certain combinations (haplotypes) could either decrease or increase the risk of specific cleft types like CPO.

What are single nucleotide polymorphisms (SNPs), and how do they relate to the genetic risk of orofacial clefts?

Single nucleotide polymorphisms (SNPs) are variations in a single nucleotide within a DNA sequence. In the context of orofacial clefts, SNPs within miRNA processing genes, such as DROSHA, can influence the risk of developing these conditions. For example, specific SNPs in DROSHA, like rs10719 and rs493760, have shown associations with cleft lip with or without palate (CL/P). These SNPs may alter the function of the gene, affecting how it processes microRNAs (miRNAs) and ultimately impacting craniofacial development. The presence of specific SNPs or combinations of SNPs (haplotypes) can increase or decrease the likelihood of developing an orofacial cleft.

What are the implications of the study findings for future research and potential interventions for orofacial clefts?

The study provides preliminary evidence that variations in the DROSHA gene are linked to non-syndromic orofacial clefts (NSOC). While the associations need further confirmation, these findings highlight the importance of miRNA processing genes in craniofacial development. Future research should involve larger sample sizes and functional experiments to validate these associations and uncover the underlying mechanisms. This could lead to the identification of potential therapeutic targets for preventing or treating orofacial clefts. Understanding the specific genetic variations and their impact on miRNA processing could open the door to personalized prevention strategies or targeted interventions during embryonic development.