Next-Generation Sequencing Data and Clinical Features in Patients with Cleft Palate and Tooth Agenesis: A Systematic Literature Review

Abstract

Objectives: The aims of this study were to explore the genetic variants identified by Next-Generation Sequencing (NGS) in patients presenting syndromic/non-syndromic cleft palate (CP) associated with tooth agenesis (TA) and to describe the observed phenotype–genotype correlations. Methods: A systematic review exploring PubMed, Scopus and Web of Science was conducted. Data extraction and bias assessment were performed. Results: From 227 screened articles, 8 studies were included. Second premolars were the most frequently missing teeth, followed by central incisors in non-syndromic CP cases. Genetic variants were most commonly reported in IRF6, FGFR1, NOTCH2, CTNND1, ZFHX4 and AXIN2. Several mutations in these genes were associated with syndromic forms such as Pierre Robin Sequence, Kallmann syndrome, and Van der Woude syndrome. Conclusions: This study suggests a potential shared genetic pathway between CP and TA and supports further exploration of TA as a possible clinical indicator of syndromic cases. NGS emerges as a valuable exploratory tool for identifying such associations, though validation in larger patient cohorts remains necessary.