Dentofacial phenotype of non-syndromic tooth agenesis patients with PAX9 mutation

Abstract

Objective·To evaluate the dentofacial phenotype in non-syndromic tooth agenesis (NSTA) patients with paired box gene 9 (PAX9) mutation. Methods·Patients with NSTA who visited the Department of Second Dental Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, between January 2016 and December 2023 received whole-exome sequencing to screen PAX9 mutation. The location and number of missing teeth were evaluated by oral pantomography, and dentofacial deformities were evaluated by X-ray cephalometrics. Results·Seven patients with PAX9 mutation were included in the study, including 3 males (42.9%) and 4 females (57.1%). The patients were 7‒31 years old at first visit, with a mean age of (19.7± 8.0) years old. All the 7 patients were PAX9 heterozygotes, of which 4 were missense and 3 were frameshift. The average number of missing teeth was 15.9±2.9. The number of missing teeth in maxilla (9.6±2.6) was slightly higher than that in mandible (6.3±2.4) (P= 0.030). Maxillary second molar (100.0%), maxillary canine (85.7%) and mandibular second premolar (85.7%) were the three most common missing teeth, while mandibular lateral incisor (14.3%) and mandibular canine (14.3%) were the two least missing teeth. Patients with frameshift mutation had more missing teeth (18.3±2.1) than those with missense mutation (14.0±1.8) (P=0.032). X-ray cephalometrics analysis results showed that the angle sella-nasion-subspinale (SNA), angle nasion-subspinale-subspinale-porion (NA-Apo) and sella-nasion (S-N) in adult patients with PAX9 mutation were significantly lower than the normal reference values, suggesting a shorter anterior cranial base and maxillary length. The frankfort horizontal plane-nasion-porion (FH-NPo) was higher than the reference value, and the Y-axis was lower than the reference value, indicating a more prognathic mandible. The angle subspinale-nasion-supramental (ANB) was lower than the reference value, indicating a skeletal angle Ⅲ malocclusion. The angle upper central incisor-nasion-subspinale (angle U1-NA) was higher than the reference value, indicating a lip inclination of maxillary central incisor. The angle lower central incisor-mandibular plane (IMPA) and lower central incisor-nasion-supramental (L1-NB) were lower than the reference values, indicating a retroclination of the mandibular central incisor, and crossbite in the maxillary and mandibular anterior teeth. Conclusion·The dentofacial phenotype of PAX9-mutated patients with NSTA is reported comprehensively. It is helpful to improve the understanding of the role of PAX9 in human maxillofacial development.