Prevalence of mandibular asymmetry in different skeletal sagittal patterns:A systematic review

Facial asymmetry refers to unbalanced proportions in size, shape, and position of bilateral structures on opposite sides of the median sagittal plane (MSP).¹  Mandibular asymmetry has a major impact because of its effects on facial appearance, as it can have permanent and marked effects on facial harmony and the smile,^2,3  and can affect social and psychological aspects^3–5  of quality of life.^4,5 

A skeletal diagnosis of mandibular asymmetry is established mainly by the location of central points of the mandible, such as Pogonion (Pog), Gnathion (Gn), and Menton (Me). Traditionally, the distance from these central landmarks to the facial MSP is calculated to quantify and classify mandibular skeletal asymmetry as mild (<2 mm), moderate (2–4 mm), or severe (>4 mm),^1,6–8  using cone-beam computed tomography (CBCT)^9,10  or posterior anterior cephalometric radiography (PA cephalogram).⁹  In 1988, Habets et al.,¹¹  introduced the asymmetry index using orthopantomograms to analyze vertical asymmetries in the mandible, in cases of ramus and/or condylar height asymmetries. Index values over 3% were considered to have vertical asymmetry. This method had been applied with better accuracy through three-dimensional exams, such as CBCT.¹² 

Studies on facial asymmetries in orthodontic and orthognathic surgery patients clinically found a prevalence of 12%–37% of mandibular asymmetries in different populations and with different anterior posterior skeletal relationships.^13–18  Some authors^6,8,19,20  showed higher prevalence of mandibular asymmetry in Class III malocclusion patients than in Class II or Class I. It was postulated that excessive growth of the mandible in Class III patients could be a risk factor for unbalanced development on both sides of the mandible.²¹ 

Knowledge of the most prevalent malocclusion with mandibular asymmetry is crucial in following up orthodontic patients to prevent deterioration and minimize risk of developing facial asymmetry. Understanding the prevalence of mandibular asymmetry could also guide researchers analyzing the etiology and morphologic features within each malocclusion. Therefore, this systematic review aimed to provide a synthesis of available evidence to answer the following focused question: “What is the prevalence of mandibular asymmetry in each skeletal sagittal malocclusion?”

Inclusion criteria were observational studies without restrictions of year and language, which presented a CoCoPop framework: Condition (Co): mandibular asymmetry diagnosed using computed tomography or PA radiographs, Context (Co): sample with skeletal Class I, II, or III malocclusion classification, Population (P): children, adolescent, and adults.

The following exclusion criteria were applied: studies with animals, studies not investigating prevalence of mandibular asymmetry, mandibular asymmetry related to syndromes and/or congenital disorders, mandibular asymmetry not confirmed by tomographic analysis or PA, or studies based on soft tissue analysis, case reports, reviews, letters, personal opinions, book chapters, and conference abstracts.

Detailed individual search strategies for each of the following were designed: PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO (Table 1). Grey literature searches through Open Grey, Google Scholar, and ProQuest were also undertaken. Google Scholar search was limited to the first 100 most relevant articles published over the last 10 years. References were stored and managed, and duplications removed, using EndNote X7 (Thomson Reuters, Philadelphia, PA, USA). The search strategy was performed in August of 2020 and was updated in March of 2021.

Study selection was completed in two phases. In phase 1, two reviewers (KE, ABT) independently reviewed titles and abstracts of all identified electronic database citations. In phase 2, these reviewers independently applied inclusion and exclusion criteria to the full article texts. The selected article written in French was translated by a speaker certificated in French. This blind process was ensured and registered using Rayyan (https://rayyan.qcri.org).²²  Reference lists of selected studies were then critically assessed.

The first reviewer independently collected the information required from the articles. The second checked this information. In cases of disagreement, a third reviewer participated for consensus decision. The following data were collected from each article: study characteristics, population characteristics, imaging diagnosis methods, criteria for Angle malocclusion classification, mandibular asymmetry diagnosis criteria, and outcome characteristics (Table 2).

The risk of bias for the selected studies was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data (2014).²³  The two reviewers independently scored the risk of bias as ‘low', ‘moderate', or ‘high', categorizing it as high when up to 49% of the items scored ‘yes', moderate when 50%–69% scored ‘yes', and low when over 70% scored ‘yes'. Any disagreement between the reviewers in each phase was resolved by discussion and agreement between them. The consensus involved a third reviewer (JV-N) for final decision.

Predictor variables were patients with sagittal skeletal malocclusions, described as Class I, II, and/or III. The only outcome variable was the prevalence of mandibular asymmetry described using frequency rates.

Mandibular asymmetry prevalence was evaluated through qualitative analysis. Heterogeneity of the studies was calculated using the Cochran's Q method and the value of I², where a P value <.05 by the Q and I² value greater than 50% was considered substantial heterogeneity. Meta-analysis of mandibular asymmetry prevalence pooling random effects with arcsine transformation (quality effects) was planned to minimize the effect of extreme prevalence on overall estimates. However, the high heterogeneity of the studies precluded the quantitative data synthesis. The agreement between both reviewers in phases 1 and 2 was tested by Cohen's kappa test. The significance level (null hypothesis) was rejected at a 5% level (P < .05).

Analyses for small-study effects, publication bias, and exploratory subgroup analyses were planned if an adequate number of studies were identified. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) system of rating quality of evidence was performed to show certainty of outcome in this review.²⁴  GRADE considered directness of evidence, consistency of results, precision of estimates, risk of publication bias, and magnitude of the effect.

Through seven databases, 5,132 citations were identified and 748 found in grey literature were added in phase 1. After removing duplicates, 2275 articles remained for screening based on title and abstract. After comprehensive evaluation of abstracts, a final sample of 18 articles was read in full text, of which five met the inclusion criteria.^6,25–28  The agreement between both reviewers was almost perfect (kappa = 0.98). Figure 1 illustrates the study selection and identification process.

Table 2 summarizes the extracted data of all studies. The five selected studies were all published between 2009 and 2018 from the following countries: Brazil,⁶  France,²⁷  Iran,²⁵  Spain,²⁶  and Turkey.²⁴  The total sample size was 1389 patients (491 females and 785 males), and no sex was reported for 114 cases extracted in one study.²⁷  Sample sizes ranged from 61 to 952 in different groups of malocclusion, with ages between 18 and 75 years. Settings of the whole sample included oral radiology clinic databases (n = 952),⁶  orthognathic surgery clinical records (n = 278)^26,28  and orthodontic clinical records (n = 159).²⁷ 

All selected studies used ANB angle for sagittal malocclusion diagnosis.^6,25–28  Four studies considered mandibular asymmetry using the horizontal position of the chin ^6,25,26,28  and, another²⁷  reported the asymmetry index to identify vertical asymmetry in the mandible.

Mandibular asymmetry ranged from 17.43% to 72.95% in the overall sample. According to mandibular asymmetry direction, horizontal chin deviation showed a prevalence of asymmetry in the Class I sample of 17.66% to 55.6%,^6,26  and 68.98% in vertical asymmetry index.²⁷  In Class II patients, prevalence of mandibular asymmetry varied from 10% to 25.5% in horizontal chin deviation,^6,26,28  and 71.7% in vertical asymmetry index.²⁷  Class III sample showed prevalence of mandibular asymmetry ranging from 22.93% to 78% in horizontal chin deviation ^6,25,26,28  and 80.4% in vertical asymmetry index.²⁷ 

Regarding methods of image diagnosis, the prevalence of mandibular asymmetry showed rates of 34.95% in overall malocclusion using PA cephalogram²⁶  and 17.43% to 72.95% using tomographic images.^6,27  According to patient settings, one study showed a sample from the database of an oral radiology clinic⁶  and four studies presented patients seeking for treatment for orthodontics²⁷  or orthognathic surgery.^25,26,28  Prevalence of mandibular asymmetry showed greater rates in patients seeking orthodontic or orthognathic surgical treatment, ranging from 34.95% to 72.95%.

Figure 2 and Table 3 present the complete list of quality assessment items. No study satisfied all risk of bias criteria. However, most of the studies were considered methodologically acceptable. Of the five studies, two showed a low risk of bias,^6,27  one showed moderate risk²⁶  and two showed high risk.^25,28  The main methodological limitations of the studies were related to representation of the target population (Question 1), since the samples were all from specific settings.

Considerable heterogeneity between studies was found in all malocclusion analyses, as seen by I² index over 96% and Q (P < .001). Due to this result, a meta-analysis wasn't performed.

Due to the limited number of studies included, publication bias analysis was not performed. Inconsistency, indirectness, and imprecision were rated as serious issues. According to the GRADE criteria, confidence in cumulative evidence was considered “very low” for the outcome evaluated (prevalence of mandibular asymmetry), due to the convenience sampling of all studies.

In this systematic review, prevalence of mandibular asymmetry was assessed overall in sagittal skeletal malocclusions and individually in Class I, II, and III malocclusions. Although quantitative analyses regarding heterogeneity exposed meaningful rates, the qualitative prevalence rates could be explored and showed new perspectives for research and clinical application in mandibular asymmetry.

Mandibular asymmetry is a craniofacial feature occurring in all types of sagittal malocclusion.^6,26,27  Greater prevalence of mandibular asymmetry in Class III patients found in this systematic review was already highlighted in many studies.^{6,8,16,19,20,26–28}  However, with regard to Class I and Class II malocclusions, prior studies showed inconclusive results. In Class II samples, some studies reported lesser prevalence of mandibular asymmetry among all malocclusions,^6,26  while another showed similar rates with Class I malocclusion.²⁷  Likewise, Class I malocclusions showed varied prevalence rates, sometimes smaller than Class III,⁶  sometimes greater.^26,27  This review brings focus to the prevalence rates among all malocclusions. Although there was strong evidence for the predominance of mandibular asymmetry in Class III patients, Class I samples also showed considerable frequency of mandibular asymmetry. The results also indicated that Class II malocclusion had the smallest prevalence of mandibular asymmetry, 9%–19% smaller than Class III patients and 4%–30% smaller than Class I patients, in agreement with Thiesen et al.⁶ 

According to patient settings, the results showed new information about mandibular asymmetry in an orthognathic surgery setting. Severt and Proffit¹⁴  analyzed a large sample of orthognathic surgery patients with facial and/or mandibular asymmetries. Asymmetric patients showed mandibular asymmetry with chin deviation, more commonly in Class III (78%) and Class I (58%) malocclusions.¹⁴  This systematic review also found a greater prevalence of mandibular asymmetry in Class III patients. A Class I sample in an orthognathic surgery setting was available in one report only,²⁶  and found 56% of patients with mandibular asymmetry, similar to findings in Severt and Proffit.¹⁴  Thiesen et al.²¹  compared mandibular asymmetry between cut-off values of chin deviation, using values under and over 4 mm as orthodontic and orthognathic surgery parameters, respectively. They found prevalence rates of 27.2% for orthodontic and 17.6% for orthognathic surgery patients. In light of these rates, it should be noted that this asymmetric condition was a common craniofacial deformity in patients seeking orthognathic treatment, except for those with Class II malocclusion, which occurred in 10%–20.5% of patients in this systematic review. These results suggest that mandibular asymmetry in surgical patients was more common in malocclusion types with potential excessive mandibular growth and/or normal growth, such as Class III and Class I malocclusions, than in patients with lower potential for mandibular growth, such as Class II patients.

Other valuable information in the current study involved the diagnosis of mandibular asymmetry using different imaging methods. Computed tomography incorporated different measurements into image analysis to enhance diagnostic methods and identify different bone regions related to asymmetry.^10,12,29,30  In terms of imaging method, the results showed that prevalence of mandibular asymmetry could be underestimated, as prevalence rates for all malocclusions increased at least 2.5 times using the asymmetry index in tomographic images.²⁷  Greater prevalence of mandibular asymmetry using CT or CBCT imaging must be viewed with caution when considering the clinical manifestation of facial asymmetry. This approach can show a patient's vertical asymmetry, as seen in ramus and condylar height, with different vertical positions in the gonion region and not necessarily due to chin deviation. Craniofacial bones located in upper facial regions, such as the maxilla, zygoma, and temporal bone (glenoid fossae), can have an important function in masking asymmetric mandibular conditions.³⁰ 

Previous studies using the asymmetry index found a difference in ramus height between sides in asymmetric Class III³¹  and Class II patients.³²  Mendoza et al.²⁷  also found considerable rates of condylar height asymmetry in all sagittal malocclusions. In this systematic review, chin deviation was the parameter mainly used to consider mandibular asymmetry.^6,25,26,28  The asymmetry index was considered only in one study in all sagittal malocclusions.²⁷  Thus, a clinical question arose after this systematic review: Are vertical asymmetries a common feature in all malocclusions? Future studies with different designs and control groups could better respond to this question.

In this systematic review, only one study included a large sample size with 952 participants⁶  and only adult samples were assessed. In addition, different criteria for mandibular asymmetry might have had an influence on the estimates of prevalence, as only one study which considered asymmetry index was included.²⁷  Additionally, comparative studies with orthodontic and orthognathic surgery patients with uniform study designs are needed to better understand the prevalence of mandibular asymmetry according to malocclusion severity. The studies only examined mandibular asymmetries in sagittal malocclusions, without considering vertical growth patterns.

A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses Protocols (PRISMA-P)³³  was drafted and registered in the Prospective Register of Systematic Reviews (PROSPERO), as CRD42020207247. In addition, reporting was based on the PRISMA 2020 checklist.³⁴ 

According to this review, the following conclusions may be considered:

• Skeletal Class III malocclusion shows the greatest prevalence of mandibular asymmetry.

• Skeletal Class II malocclusion has the lowest prevalence of mandibular asymmetry.

• Vertical asymmetry shows a marked prevalence in all malocclusions.

• However, conclusions should be interpreted with caution due to convenience sampling and low-quality study outcomes.

Support

This study received partial support from Capes (Financial code 001) and NIH grant NIDCR R01 DE024450.

Competing Interests

The authors declare no competing interests.

Data Availability Statement

Data are available on request to the corresponding author by e-mail.