Exploring Sex-Specific Genetic Variants in Cleft Lip and/or Palate: A Literature Review

Abstract

Clefts of the lip and/or palate (CL/P) represent the most prevalent congenital anomalies in the oropharyngeal region, originating from defects in craniofacial fusion processes between the 5th and 12th weeks of embryonic development. The incidence of CL/P varies significantly across geographical regions, ethnic groups, and genders, with males exhibiting a higher prevalence of cleft lip and females more frequently affected by isolated cleft palate. Genetic studies have identified sex-specific variants that contribute to these differences, notably the MSX1 gene in males and GTF2A1L and LTBP1 genes in females. Environmental factors, including maternal smoking, alcohol consumption, and nutritional deficiencies, along with hormonal influences such as estrogen, play critical roles in the etiology of CL/P. Epigenetic mechanisms, particularly DNA methylation, also contribute to the phenotypic variability. Understanding the genetic and molecular mechanisms underlying CL/P is essential for early diagnosis and personalized treatment strategies. Prenatal genetic screening and counseling can mitigate risks and improve outcomes. Future research should prioritize large-scale genomic studies to elucidate the complex interactions between genetic and environmental factors in CL/P development, aiming for targeted and personalized therapeutic interventions.