The distribution of the cleft types between male and female patients did not vary significantly. These results are in concordance with other research reports . Still, the majority of the patients belonged to the CL + P L group (38.3%) in agreement with relative research investigations [9, 15, 20].
In current literature, tooth agenesis is also reported as the most frequent dental anomaly among cleft patients [3,4,5,6,7]. Interestingly, in the CL + P B group, the frequency of tooth agenesis was significantly higher among males. All the other cleft groups showed no differences in the distribution of dental anomalies neither among them nor between genders. Other authors have also reported no differences in dental anomalies between genders [14, 21].
Tooth agenesis in the non-cleft population ranges at considerably smaller numbers than the 50% found in our study. In a cross-sectional study conducted by Lagana  in a large sample of 5005 individuals, the prevalence of tooth agenesis was 7,1%, which is in similar range with the reports of Rakhshan  (0.15–16.2% excluding the third molars). Lagana  also reported that the missing dental units are often the distal teeth in each group of homogeneous teeth: the upper and lower third molars, lateral incisors, and lower second premolars.
A meta-analysis conducted by Polder  included 33 studies and investigated the prevalence of non-syndromic tooth agenesis. The results showed that the prevalence of dental agenesis in females was 1.37 times higher than in males. Most individuals were missing one or two permanent teeth, with very few missing more than six. Also, the mandibular second premolar was the most affected tooth, followed by the maxillary lateral incisor and the maxillary second premolar.
The results of our study confirm Dermijian’s reports who postulated that the mechanisms controlling dental development are independent of sexual and somatic maturity thus being influenced by other etiologic factors as clefts . Baek and Kim also reported no differences in the distribution of dental anomalies between Korean male and female patients; whereas Wangsrimongkol et al. examining a sample of 280 Thai patients suggested a gender-dependent pattern in the agenesis of maxillary lateral incisors and maxillary second premolars [4, 18].
In regard to the association of the investigated dental anomalies with the type of cleft, our results showed no differences between the cleft groups coming, thus in contrast with those of Paranaiba et al., where patients with unilateral cleft lip and palate (CLP U) were more frequently affected by dental anomalies than those with bilateral cleft lip and palate (CLP B) . In the same study, CLP U and CLP B were significantly more affected by tooth agenesis than other cleft types. Additionally, Menezes and Vieira reported that in a sample of 146 cleft patients the CL+ P B patients presented more dental anomalies than individuals with incomplete CLP . According to another group of researchers CL + P U had a higher prevalence of tooth agenesis, even in the non-cleft area, in comparison to the normal population .
In our sample, the upper lateral incisors followed by the upper right premolar were found missing most frequently in the cleft area. Still, a strong association between the side of the cleft and tooth agenesis was found for the two maxillary quadrants (Q1 and Q2) in CL + P L and in CL + P R patients and for the two mandibular quadrants (Q3 and Q4) in CP patients. In regard to the missing laterals, the findings are in accordance with a study conducted with 203 cleft patients in Brazil stating that agenesis of lateral incisors in CLP U patients was much more frequently noted in the cleft side rather than in the non-cleft side . Still, several research projects conclude that agenesis occurs mainly at the cleft side and the most prevalent missing tooth is the lateral incisor [4,15,, 10, 14–16]. Even in cases of isolated soft tissue cleft lip (the alveolus being intact), dental abnormalities, including tooth agenesis, were significantly more frequent in the cleft side . In agreement with our results, several studies report the maxillary second premolars followed by their mandibular counterparts as the most frequent missing teeth outside the cleft area, thus indicating a genetic link between cleft and tooth agenesis [6, 14, 17].
However, the association between the maxillary right (Q1) and left quadrants (Q2) regarding tooth agenesis was found to be significant. A large percentage (52.5%) of the 40 patients presenting with tooth agenesis in Q1 presented tooth agenesis also in Q2. These results indicate that if a patient presents with tooth agenesis in Q1 is more likely to have agenesis in Q2 compared to a patient who does not present with agenesis in Q1. Still, a strong association was found between Q1 and Q3 indicating that individuals with tooth agenesis at Q1 are more likely to have tooth agenesis also in Q3. To our knowledge in current literature, there are no similar reports examining the association of tooth agenesis quadrants.
The quadrant association findings indicate that tooth agenesis is not directly related to the disruptive osseous defect which occurs at the cleft side but is rather a genetically controlled anomaly related to the orofacial cleft possibly through multifactorial genetic links. These results confirm findings of previous research investigations, which suggest that tooth agenesis encompassing multiple missing teeth has been clearly identified under genetic control of multifactorial inheritance [28,29,30]. Several of these critical genetic controls assume a mutual part in the development of orofacial clefts .
The results of our study will be of valuable help to the clinicians who treat non-syndromic orofacial cleft patients in developing improved interdisciplinary treatment protocols. The high prevalence of tooth agenesis occurred especially in the maxillary arch could be further investigated with the use of the tooth agenesis code (TAC) method.
Limitations of the study
The limitations of this study can be primarily attributed to the small sample size especially for the groups of cleft lip only (CL U R and CL U L) and cleft palate only (CP). Still, oral clefts comprise a rare disease and collection of large samples can be very challenging. Furthermore, all patients were of Caucasian origin and this constitutes another limitation. In order to achieve an accurate representation of the different cleft types, distribution in non-syndromic oral cleft patients' further investigations should examine different ethnic groups and obtain larger sample sizes.