While hypodontia has been studied in the literature, the prevalence of MLIA is not as well reported. This study provides insight into the characteristics of MLIA and bring awareness to MLIA as a subtype of tooth agenesis. By initially screening a large number of orthodontic patients (7,227 patients), we found that non-syndromic tooth agenesis had a prevalence of 3.3%, which falls toward the lower end of the previously reported range of 2.5–13.4% [1, 3, 5,6,7,8]. Furthermore, the 90 patients diagnosed with MLIA in our orthodontic patient sample corresponded to a prevalence of 1.25% for the congenitally missing maxillary lateral incisors. This is slightly higher than what was found in the previous 2017 study by Kabbani et al., which reported a prevalence of 1.15% for MLIA in Syrian children (a non-orthodontic sample) [29]. In addition, similar to the earlier studies, we found that maxillary lateral incisors were the second most commonly congenitally missing teeth (excluding third molars) [1, 3, 5, 6]. This differs from what Vahid-Dastjerdi et al. described in their 2012 study of the Iranian population. Although their MLIA prevalence (35.6%) in the TA patients was similar to ours (37.5%), they reported the maxillary lateral incisors as the most common congenitally missing tooth [30]. In this study, we established that 37.5% of the TA patients had at least one missing maxillary lateral incisor. Furthermore, bilateral MLIA was diagnosed significantly more often than unilateral MLIA (64.4 vs. 35.6%, respectively). This differs from the 2018 study of Brazilian orthodontic patients by Souza-Silva et al., which found that 19.1% of their non-syndromic hypodontia patients were missing only one maxillary lateral incisor and 13.2% presented with bilateral MLIA [23]. However, they did report that the maxillary lateral incisor was the most frequent tooth to be congenitally missing symmetrically.
On the other hand, our study supports the data reported in the meta-analysis by Polder et al. (2004) that found that among patients with affected maxillary laterals, bilateral MLIA occurred more often than unilateral ranging between 50.9 and 57% of the time [5]. They reported that this was unique to MLIA, since in the hypodontia cases involving agenesis of other teeth, unilateral tooth agenesis was more common. Similarly, two other studies of MLIA in Portuguese populations (2005 and 2010) reported bilateral MLIA in 55.2% and 52% of their patients, respectively [19, 31]. Finally, a 2009 study of Brazilian orthodontic patients by Garib et al. found that 51.6% of their MLIA patients presented with bilateral missing lateral incisors [26]. These studies, in addition to ours, indicate that there may be a predilection for bilateral MLIA over unilateral MLIA. These are significant findings, since this phenotype may present particularly challenging consequences phonetically and aesthetically for patients.
In patients with MLIA in order to establish what is considered a normal Angle class I buccal occlusion, space must be opened orthodontically and subsequently restored. This allows maintenance of the canine in its natural position and intercuspation with the first premolar and preserves canine-protected occlusion. However, space opening could be contraindicated in certain patients, for example, those with protruded incisors [2]. Additionally, this commits the patient to a lifetime of maintenance of a fixed or removable restoration at the lateral site. Alternative options such as autotransplantation of a maxillary premolar with incompletely formed roots into the lateral space or complete closure of the lateral space with protraction and subsequent reshaping of the maxillary canines are also frequently employed. Both of these options present difficulties with orthodontic mechanics and aesthetics of replacing a lateral incisor with a larger canine or premolar [2]. Asymmetrical cases (i.e., unilateral MLIA) present even greater aesthetic concerns.
When looking at unilateral presentation of tooth agenesis, the literature review by Rakhshan (2015) reported that hypodontia affects the patient’s left and right sides equally [32]. Our findings support this review as we did not find any significant difference in the prevalence of the left versus right missing lateral incisors (7.08% vs. 6.25%, respectively). However, our data contradict the 2005 study by Pinho et al., which showed that unilateral MLIA on the right was seen more often than on the left (60.3% vs 39.7%, respectively) [31]. This was found to be borderline significant with p value of 0.06.
Studies have shown that TA prevalence varies with race, ethnicity, and the geographical distribution of the population. The prevalence of Caucasians diagnosed with TA, summarized by Polder et al. in a 2004 meta-analysis, varied from 3.9% in North America, to 5.5% in Europe, and to 6.3% in Australia [5]. There are less data regarding this disorder in African-Americans. A 2008 study by Harris and Clark reported that 11% of African-Americans had congenitally missing teeth [33]. This was significantly lower than the prevalence of 27% they saw in the Caucasian Americans. However, their study included the absence of third molars in their investigation, which explains their much higher rates compared to the ones reported in the earlier studies. TA rates of Asians also vary by locations and have been reported as 6.9% in Chinese, 9.4% in Japanese, and 11.2% in Korean populations [34,35,36]. However, these studies do not differentiate between the prevalence of the different types of TA. In our study, we evaluated the racial/ethnic differences in patients with MLIA. We found that while the Caucasians made up the majority (80%) of our sample of patients with congenital tooth agenesis, they had the lowest MLIA prevalence (34.4%). However, this was not statistically significant from the 51.4% in African-Americans, 42.9% in Asians, and 50% in Hispanics. Our data also differ from a recent (2021) study by Eshgian et al., which found that 20.65% of the Hispanics and 6.67% of African-Americans with dental anomalies had congenitally missing teeth [37]. Interestingly, none of their Caucasian or Asian patients presented with TA. Although we were able to investigate racial/ethnic differences in our patient population, the low percentage of Hispanic and Asian TA patients in our sample (2.5% and 2.9%, respectively) presented a limitation for our study.
Previous publications have also indicated that females are more likely to display tooth agenesis. In the 2004 meta-analysis by Polder et al., females were reported to be 1.37 times more likely than males to have non-syndromic tooth agenesis [5]. Another study by Souza-Silva et al. described non-syndromic TA as more common in females (prevalence ratio of 3.49) [23]. Rakhshan’s 2015 review also indicated that females have a greater predilection to non-syndromic hypodontia at a rate of 2:3 when compared with males [32]. Furthermore, the 2005 study by Pinho et al. found the MLIA prevalence to be 1.5% in females and 1.1% in males, which was significant (p value < 0.02) [31]. In our study, we also found that non-syndromic TA was more common in females than males (57.1% vs. 42.9%, respectively). In our Asian and Hispanic patients, MLIA was only diagnosed in females. However, unlike Pinho et al., we did not see an increase in risk of MLIA in our overall female population. In contrast, we actually found that Caucasians males present with MLIA statistically more than females. According to our study, overall, females may be more likely to have non-syndromic congenitally missing teeth but not necessarily MLIA.
In this study, we also found that 42% of MLIA patients were diagnosed with agenesis of another tooth type. This is higher than the 2010 study by Garib et al., which showed that 23 of 126 patients (18.2%) had MLIA and another missing tooth [26]. An earlier 2005 study by Pinho et al. also reported that 12.8% of their 219 MLIA patients were missing another tooth [31]. This lower percentage could be explained by the fact that 55 of their 219 patients could not be confirmed for this information and were excluded.
This potential of another congenitally missing tooth is of clinical importance in managing young patients with MLIA, and they should be monitored for other missing teeth. If a young patient present with a missing maxillary lateral, they should be closely monitored for development of the second premolars as they are frequently missing [31]. The restorative dilemma of missing laterals poses a difficult situation as mentioned previously. When other teeth are missing, an even more complex situation develops. Early detection can help in preparing the patients and developing a treatment plan for space closure or long-term restoration. Molecular genetic studies in the future will contribute to identifying the variation in the different patterns of expression of hypodontia.
Furthermore, patients with unilateral MLIA may have an increased risk for the contralateral incisor to be peg-shaped. Hua et al. in a 2013 meta-analysis reported that unilateral MLIA was associated with peg-shaped maxillary laterals 55.5% of the time [38]. Additionally, in the 2010 study by Garib et al., 38.8% of all MLIA patients had peg laterals [26]. They reported an even higher association between unilateral MLIA and peg-shaped contralateral incisor (80.3%). Similarly, in our study we establish a statically significant association between MLIA and peg lateral incisors. We found that 62.5% of unilateral MLIA patients presented with peg laterals. This 62.5% falls within the range reported by Hua et al. and Garib et al. [26, 38]. The literature suggests that the mechanism of agenesis of the lateral incisor is similar to that of the peg shape and that peg laterals are a mild form of hypodontia. The association of peg laterals with unilateral MLIA from our study supports this concept [38].
Several studies involving non-syndromic tooth agenesis have also indicated a possible correlation with other dental anomalies [2, 20, 21]. Cases of MLIA have shown to present with other coronal or radicular malformations, delayed or ectopic eruption of other teeth, impacted teeth, or transpositions. In general, the most frequent tooth abnormality is related to tooth size and is usually seen in maxillary lateral incisors (excluding third molars).
Peg-shaped laterals are not the only anomaly associated with missing lateral incisors. MLIA patients may also be diagnosed with other coronal or radicular malformations, transposition, or impactions [2, 20, 21]. In our study, we identified three patients with microdonts (other than peg laterals); however, none of them presented with MLIA. Furthermore, while tooth transposition may occur in about 0.33% of the general population [22], we did not identify any cases in our patients with non-syndromic TA.
Concerning dental impactions, Sacerdoti and Baccetti have reported a significant association between missing laterals and palatally displaced canines [24]. The maxillary canine is the most frequently impacted tooth after third molars and is followed by the second premolars [25]. In the general population, prevalence of palatally displaced canines ranges between 0.8 and 2.8%; however, Al-Nimiri and Bsoul showed that 12.6% of subjects with MLIA also had palatally impacted canines [25]. In our study, 7.5% of the TA patients also had an impaction. This falls within the range of the prevalence of impacted teeth reported in the general population (5.6–18.8%, excluding third molars) [39]. The overall prevalence in our population is similar to the general population, and there is no difference between MLIA patients and other hypodontia patients. However, unlike Montasser and Taha’s study, which reported that maxillary canines were the second most commonly impacted tooth (after mandibular second premolars) [40], we found that maxillary canines were statistically the most likely tooth to be impacted among all hypodontia patients in our study.
Previous studies have correlated an increase in the prevalence of TA with the Class III skeletal or dental relationship [30, 41]. Celikoglu et al. also found that ectopic eruption was significantly more prevalent in MLIA patients [41]. While these were not variables included in our study, future investigations can further examine the relation between the skeletal and dental classifications and the specific type of tooth agenesis. In addition, these studies can evaluate how this distribution compares to that of the general population.
Due to the complex nature of successful dental development, small changes in eruptive movement can lead to difficulties in tooth movement, function, and esthetics. It is still unclear how these anomalies are genetically related to missing lateral incisors, but it is likely that there are some epigenetic and environmental factors contributing to these conditions and should be studied in the future [32].
