Gene mutations and chromosomal abnormalities in syndromes with tooth agenesis

Abstract

This study aims to review the pathogenic mechanisms and clinical manifestations in syndromes with tooth agenesis (TA). Online Mendelian Inheritance in Man and PubMed databases were searched for a comprehensive review. Previous publications reported complicated aetiologies of syndromic TA. Gene mutations in conserved signalling pathways (WNT, EDA, SHH, FGF, and TGF‐β/BMP) and crucial molecules (PAX9, PIXT2, IRF6, the p53 family, and subunits of RNA polymerase III) are the main causes of syndromic TA. In the process of odontogenesis, antagonistic or synergistic interactions are demonstrated in patients and murine models. Mutations in some genes (WNT10A, WNT10B, AXIN2, ANTXR1, MSX1, EDA, EDAR, and EDARADD) can result in both syndromic and isolated TA. In addition, chromosomal anomalies are also responsible for syndromic TA (Down syndrome, Wolf‐Hirschhorn syndrome, Williams syndrome, and Pierre Robin sequence). The causes and manifestations of syndromic TA are highly complex, and this constitutes a clinical challenge. Mutations in signalling pathways and crucial molecules as well as chromosomal anomalies are responsible for syndromic TA. And there are overlaps between the causative genes of syndromic and isolated TA.

Identification of novel candidate genes associated with non-syndromic tooth agenesis in Mongolian families

“…Some examples of syndromic TA include cleft lip/plate [9], ectodermal dysplasia [10], Axenfeld-Rieger syndrome, and Witkop syndrome [11][12][13]. The etiology of TA can be attributed to genetic or environmental factors [14][15][16][17]. However, genetic factors play a more signi cant role in the pathogenesis of TA [18,19].…”

“…MSX1 and PAX9 are among the rst genes associated with TA, and their protein products act as transcription factors essential for the tooth germ's development from mesenchymal cells [30,31]. Mutations in AXIN2 and WNT10A can disrupt the Wnt signaling pathway, which is vital for tooth development, with AXIN2 involved in tooth germ formation and WNT10A in differentiation of dental mesenchymal cells [15]. Recently, it has been shown that PITX2 contributes to TA and is involved in the early stages of tooth development, including the formation of tooth germs and bud morphology [32].…”

Crosstalk between stomatology and medical genetics: Viewpoints of Chinese scholars

“…This special issue comprises nine invited reviews from OGDRD committee members, focusing on congenital dental abnormalities such as hereditary enamel and dentin defects (Dong et al, 2023; Su et al, 2023; Yuan et al, 2023; Zhang et al, 2023), tooth agenesis (Lan et al, 2022), multiple idiopathic cervical root resorption (Wang et al, 2022), craniofacial and oral malformations including non‐syndromic skeletal Class III malocclusion (Zhou et al, 2022), mandibular coronoid process hyperplasia (Wang, 2022), and hemifacial microsomia (Luo et al, 2023).…”

“…Similarly, Su et al (2023) provided an overview of 13 syndromic dentin defects, many exhibiting accompanying bone malformations or abnormal bone metabolism (Su et al, 2023). Meanwhile, Lan et al (2022) described the syndromes associated with tooth agenesis, including monogenic diseases with mutations in almost 20 genes and several chromosomal anomalies (Lan et al, 2022). Furthermore, Wang et al (2022) comprehensively described 20 systemic diseases or syndromes associated with coronoid process hyperplasia (Wang, 2022).…”

“…The biological roles of genes involved in syndromic tooth agenesis, enamel, or dentin defects may share similar or distinct mechanisms from non‐syndromic defects. The mutations in these pathogenic genes may disrupt the conserved or non‐classical signaling pathways and shed light on the understanding of isolated or non‐syndromic dental defects (Dong et al, 2023; Lan et al, 2022; Su et al, 2023).…”