Original Article

All in the family: Use of familial information in orthodontic diagnosis, case assessment, and treatment planning*

Mandibular retrognathism is a type of malocclusion that refers to an abnormal posterior position of the mandible as a result of a developmental abnormality. From the literature, it is evident that the mandibular growth pattern is determined by the intramembranous ossification of the mandibular body and endochondral ossification of the condyle. Matrilin-1 is a cartilage extracellular matrix protein, and matrilin-1 gene (MATN1) polymorphisms have been found to be involved in dental malocclusions of humans. In this study, we aimed to examine the association between MATN1 polymorphisms and the risk of mandibular retrognathism, in a case-control study with a South Indian population.

Eighty-one patients with mandibular retrognathism (SNB, <78°) and 71 controls having an orthognathic mandible (SNB, 80° ± 2°) were recruited. In both the patient and control groups, subjects with an orthognathic maxilla (SNA, 82° ± 2°) were included. Three single nucleotide polymorphisms of the MATN1 gene (rs1149048, rs1149042, and rs1065755) were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The statistical association analysis was performed using the chi-square test. Pair-wise linkage disequilibrium was computed, and haplotypes were compared between subjects and controls. Nonparametric tests were used to compare cephalometric measurements between groups.

No polymorphic site deviated from Hardy-Weinberg equilibrium in the controls. The rs1149042 genotypes and alleles were found to be associated with reduced risk of mandibular retrognathism. Furthermore, rs1149042 genotypes were associated with mandibular measurements (SNB and ANB). There was no strong and consistent linkage disequilibrium linkage disequilibrium across two different single nucleotide polymorphisms and haplotypes were not associated with mandibular retrognathism.

The results of our study suggest an association between the MATN1 gene polymorphisms and mandibular retrognathism.

The field of genetics emerged from the study of heredity early in the 20th century. Since that time, genetics has progressed through a series of defined eras based on a number of major conceptual and technical advances. Orthodontics also progressed through a series of conceptual stages over the past 100 years based in part on the ongoing and often circular debate about the relative importance of heredity (nature) and the local environment (nurture) in the etiology and treatment of malocclusion and dentofacial deformities. During the past 20 years, significant advancements in understanding the genomic basis of craniofacial development and the gene variants associated with dentofacial deformities have resulted in a convergence of the principles and concepts in genetics and in orthodontics that will lead to significant advancement of orthodontic treatments. Fundamental concepts from genetics and applied translational research in orthodontics provide a foundation for a new emphasis on precision orthodontics, which will establish a modern genomic basis for major improvements in the treatment of malocclusion and dentofacial deformities as well as many other areas of concern to orthodontists through the assessment of gene variants on a patient-by-patient basis.

Craniofacial skeletal dysplasia can lead to different skeletal malocclusions. Both environmental factors and heredity contribute to the formation of malocclusions. There are strong familial tendencies in the development of Angle's Class II and III malocclusions. Cases such as opposite-typed (Class II and III) malocclusions with skeletal and dentoalveolar discordance in siblings or dizygotic (DZ) twins have seldom been reported. We describe the rare case of a pair of opposite-sex DZ twins with completely different skeletal malocclusions, and discuss the clinical considerations for treatment. The patients were twins aged 13 years and 4 months. The girl had mandibular prognathism and a Class III dentoskeletal relationship, whereas the boy had skeletal Class II with mandibular retrusion. Several morphological traits have been implicated with hormonal effect. However, there was no evidence of whether the masculinization effect had any impact on jaw size in the female fetus or whether this effect lasted into adolescence. We suggest that, although DZ twins share the same growth environment, genetic or other unknown extrinsic factors can result in discordance of characteristics of the craniofacial skeleton, dentition, and occlusion.

Analysis of family members is central to understanding the causation of biological variation, either genetic or environmental. Rarely, however, is the answer one or the other; variation in the craniofacial complexes, including occlusal variation (“malocclusion”), is almost always some complex combination of nature and nurture. Heritability is the proportion of a trait's variation that, under ideal, simplified conditions, is due to genetic variation. It, in fact, implies nothing about trait size or treatment limits based on some presumed genetic “predetermination.” This article overviews the genetic and environmental sources of variation that generate a trait's phenotype to help clarify the interpretation and limitations of a trait's “heritability,” which is a term often overinterpreted in the orthodontic literature. Applications of genetic studies to the causation of malocclusion also are reviewed, showing that skeletal variation has a substantial genetic component, but there is little or none for “tooth-based” variations such as tooth positions, rotations, and displacements.