Global trends and hotspots of genetic research on non-syndromic cleft lip with or without cleft palate: a bibliometric and bioinformatics analysis

Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) accounts for 70% of orofacial cleft cases worldwide and causes physical dysfunction and psychological burden. Prior bibliometric studies have outlined the general NSCL/P research landscape; however, a systematic overview targeting the genetic dimension, evolutionary trends since the Human Genome Project, and dual-database cross-validation remains limited. This study mapped the global bibliometric landscape of NSCL/P genetics, identified shifting research paradigms, and functionally validated candidate genes through bioinformatic analyses of environmental risk factors. Methods Publications from January 1990 to 31 January 2026, were retrieved from the Web of Science Core Collection and analyzed using bibliometric tools, including R-Bibliometrix, VOSviewer, and CiteSpace. Subsequently, Scopus publications were searched using the same search strategy for cross-validation. Finally, toxicant-induced and NSCL/P-related genes were screened from the GeneCards database to identify overlapping targets, followed by construction of a protein–protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analysis to characterize potential functional pathways. Results A total of 1,511 eligible publications were analyzed, covering 86 countries and regions, 1,766 institutions, 6,061 authors, and 383 journals, with rapid publication growth observed between 2018 and 2021. The United States led in output and citations alongside the University of Iowa and Murray, Jeffrey C., as key contributors. Keyword clustering categorized the current studies into four major categories: genetic analysis methodologies, developmental biology and phenotypes, epidemiology and environmental factors, and molecular regulatory mechanisms. Alcohol- and nicotine-induced overlapping pathogenic genes were identified with enriched pathways involved in the regulation of embryonic craniofacial development, cell proliferation, and apoptosis. Conclusion This study clarified the publication trends, key research forces, disciplinary distributions, and hotspots in NSCL/P genetics, revealing an ongoing shift in research focus. In silico network analyses of public databases identified distinct molecular pathways mediating alcohol- and nicotine-induced developmental disorders. These findings provide reliable evidence for future mechanistic exploration of NSCL/P pathogenesis.