The relationship between third molar agenesis and craniofacial morphology: a systematic review and meta-analysis.

BACKGROUND: Agenesis of third molar agenesis has a higher incidence than other tooth development anomalies. Previous research identified a potential correlation between third molar agenesis and specific craniofacial morphology; however, no systematic review and meta-analysis on this topic currently exists. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the association between third molar agenesis and craniofacial sagittal and vertical morphology. SEARCH METHODS: An electronic search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library without restrictions on publication year or language; this was supplemented by the manual retrieval of relevant literature. SELECTION CRITERIA: Cross-sectional studies that compared craniofacial morphology using angular and linear measurements obtained from lateral cephalography between patients with third molar agenesis and those without were included. DATA COLLECTION AND ANALYSIS: The quality assessment of the enrolled articles was evaluated by the Joanna Briggs Institute critical appraisal tool. Meta-analysis and sensitivity analysis were performed by Review Manager software (The Cochrane Collaborative, version 5.4, Cochrane IMS). RESULTS: A total of seven studies were included. Meta-analysis demonstrated that the ANB (mean differences (MD) = -0.75, 95% CI: -1.31 to -0.19, P < 0.01), palate length (ANS-PNS, MD = -1.68, 95% CI: -2.24 to -1.11, P < 0.01), and mandibular length (Go-Pog, MD = -0.36, 95% CI: -0.59 to -0.13, P < 0.01) were smaller in patients with third molar agenesis. With regard to vertical craniofacial morphology, the mandibular plane angle (MP-FH; MD = -1.88, 95% CI: -3.45 to -0.31, P = 0.02), gonial angle (gonial angle; MD = -1.73, 95% CI: -2.69 to -0.77, P < 0.01) and lower face height (lower face heigh angle; MD = -1.36, 95% CI: -1.94 to -0.77, P < 0.01) were smaller in patients with third molar agenesis, indicating a flatter or brachyfacial skeletal pattern. CONCLUSIONS: The results of this study suggest that third molar agenesis maybe associated with a reduced maxillary length and a flatter mandible. However, these findings need to be interpreted with caution due to inconsistencies in the certainty of evidence. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42023448226).

A comparative retrospective study on the prevalence and therapeutic treatment of dental agenesis between healthy children and children with systemic disease or congenital malformation.

BACKGROUND: Dental agenesis (DA) in the permanent dentition is one of the most common dental anomalies, with a prevalence up to 2-10%. Therefore, the aim of this retrospective study was to investigate the prevalence and therapeutic treatment of DA in healthy children (HC) compared to children with systemic disease or congenital malformation (SD/CM). METHODS: Out of 3407 patients treated at the Department of Paediatric Dentistry of the Justus Liebig University Giessen (Germany) between January 2015 and December 2020, a total of 1067 patients (594 female, 473 male) aged between 4.5 and 18 years were included in this study due to DA. Besides the patients' general medical history and therapeutic treatments, panoramic radiographs were analysed. RESULTS: In contrast to the HC group with 9.7% DA, the SD/CM group showed a significantly higher prevalence of DA (19.8%; p < 0.05). The latter group was further classified into children with ectodermal dysplasia (4.4%), down syndrome (8.2%), cleft lip and palate (4.4%), intellectual disability/developmental delay (16.4%), and other genetic/organic diseases without intellectual disability (45.9%). Regarding therapeutic treatments, the HC group (59.5%) was significantly more often treated with an orthodontic gap opening compared to the SD/CM group (42.6%; p < 0.05), followed by orthodontic gap closing 36.5% in the HC group and 22.9% in the SD/CM group (p < 0.05), whereas no treatment was predominantly performed in the SD/CM group (37.7%) compared to the HC group (4%; p < 0.05). Furthermore, 50% in the SD/CM group required general anaesthesia for therapeutic treatment (vs. 8.1% in the HC group; p < 0.05). CONCLUSIONS: Children with SD/CM suffered more often from DA compared to HC that underlines multi- and interdisciplinary treatment of utmost importance. Furthermore, due to intellectual disability, common treatment methods can be complicated by insufficient compliance. This fact underlines the importance of an early attempt to establish the necessary cooperation enabling children with SD/CM to receive therapy.

Maxillary lateral incisor agenesis is associated with maxillary form: a geometric morphometric analysis.

BACKGROUND AND OBJECTIVE: Agenesis of the maxillary lateral incisor occurs in up to 4% of all individuals and requires multidisciplinary treatment. Its developmental origins, however, are not fully understood. Earlier studies documented genetic factors contributing to agenesis but also an association with craniofacial morphology. In this study, we assessed the association between maxillary morphology and lateral incisor agenesis by a geometric morphometric approach to disentangle the roles of developmental plasticity and genetic factors. MATERIALS AND METHODS: We quantified the maxillary alveolar ridge by 19 two-dimensional landmarks on cross-sectional images of 101 computed tomography scans. We compared the shape and size of the alveolar ridge across patients with unilateral or bilateral agenesis of maxillary lateral incisors and patients with extracted or in situ incisors. RESULTS: The maxillary alveolar ridge was clearly narrower in patients with agenesis or an extracted incisor compared to the control group, whereas the contralateral side of the unilateral agenesis had an intermediate width. Despite massive individual variation, the ventral curvature of the alveolar ridge was, on average, more pronounced in the bilateral agenesis group compared to unilateral agenesis and tooth extraction. CONCLUSIONS: This suggests that pleiotropic genetic and epigenetic factors influence both tooth development and cranial growth, but an inappropriately sized or shaped alveolar process may also inhibit normal formation or development of the tooth bud, thus leading to dental agenesis. CLINICAL RELEVANCE: Our results indicate that bilateral agenesis of the lateral incisor tends to be associated with a higher need of bone augmentation prior to implant placement than unilateral agenesis.

Association between dental agenesis and delay in dental development: a preliminary study in a Spanish paediatric population in relation with Dental Anomaly Pattern (DAP).

BACKGROUND: The association between dental anomalies has been studied, giving rise to the concept of Dental Anomaly Pattern (DAP). Tooth agenesis has been associated with alterations such as molar infracclusion, taurodontism and delayed dental development. The aim of this study was to evaluate the dental development pattern in patients with non-syndromic dental agenesis, in comparison with a control group. METHODS: Dental and chronological age was analysed in a sample size of 204 orthopantomographs divided into a study group (n = 104) and a control group (n = 100) with the Demirjian Method. Intra and intergroup differences in chronological and dental age, and the correlation between them were calculated by statistical analysis with a 95% confidence level (p < 0.05). RESULTS: Dental age exceeded chronological age both in the control group and in the study group. Statistically significant differences (p = 0.004) were found when comparing the difference between chronological and dental age in the study (-0.16 ± 1.12) and control group (-0.58 ± 0.90). Regarding sex and age intergroup differences, the results were only statistically significant in the girls' group (p = 0.017), and the age over 8 years old (p < 0.05). There were no significant differences in tooth development depending on the number of missing teeth or the affected tooth group, but there was a delay in the development of the homologous tooth contralateral to the absent one in 14.9% of patients. CONCLUSIONS: The difference between chronological and dental age in permanent dentition is significantly lower in Spanish children with non-syndromic agenesis compared to a control group, presenting a lower dental age than chronological age than children without non-syndromic agenesis.

Third molar agenesis: Prevalence and Association with agenesis of other teeth in a Turkish population.

BACKGROUND: Tooth agenesis is the congenital lack of one or more primary or permanent teeth and it is the most frequently seen dental anomaly. The prevalence of third molar agenesis is significantly higher than the agenesis of other teeth varying from 10% to 40% and shows geographical variance. AIMS: The aim of this study was to investigate the prevalence of third molar agenesis and its association with other tooth agenesis of jaws. SUBJECTS AND METHODS: A total of 594 Turkish subjects with or without agenesis of third molars (M3) were included in the study. Dental records and panoramic radiographs were evaluated for M3 agenesis, hypodontia and hyperdontia. Significant differences in the prevalence rate of M3 agenesis between genders among with evaluation of coexistence of M3 and other tooth agenesis were determined by Fisher's exact test. RESULTS: The prevalence of M3 agenesis was determined as 28.7% with no statistically significant gender or location difference. Most common form of M3 agenesis involved one molar followed by two, four and three molars. Agenesis of other teeth was seen among both patient groups with and without M3 agenesis, without significant difference. CONCLUSIONS: Turkish population with M3 agenesis did not show increased prevalence of other tooth agenesis, indicating no association between occurrence of agenesis of other teeth and M3.

Tooth agenesis: part 2. Orthodontic treatment and prosthetic possibilities.

Dental agenesis has a great clinical significance due to its frequency during daily practice and the therapeutic problems that can arise from it. This paper will explore all the aspects to consider in order creating a proper multidisciplinary treatment plan: in particular, orthodontic, prosthetic and implantologic therapeutic alternatives are described for the rehabilitation of the different areas of the dental arches. In fact, dental agenesis is a problem that often requires the intervention of specialists from the different fields of dentistry and its treatment must meet aesthetics needs, stomatognathic function and patient satisfaction.

Tooth agenesis: part 1. Incidence and diagnosis in orthodontics.

Dental agenesis has a great clinical significance due to its frequency during daily practice and the therapeutic problems that can arise from it. This paper will explore the incidence of dental agenesis, its diagnosis and how this anomaly affects the teeth differently. The second subsequent paper will look at its treatment and management.

Novel rare variations in IRF6 in subjects with non-syndromic cleft lip and palate and dental agenesis.

OBJECTIVE: Subjects with cleft lip and palate (CLP) present high prevalence of dental agenesis. Among candidate genes for these phenotypes is IRF6. However, genetic studies do not analyze dental agenesis as a phenotype associated with cleft. Therefore, we investigated the frequency of rare and novel variations in IRF6 in subjects with non-syndromic unilateral cleft lip and palate (NSUCLP), with and without dental agenesis. SUBJECTS AND METHODS: Genomic DNA samples of 100 subjects with NSUCLP with and without dental agenesis and 50 controls were sequenced. IRF6 mutational screening was conducted by direct sequencing. RESULTS: Ten new and rare missense variations were identified, two in the group cleft with agenesis and eight in the group cleft without agenesis, and none were found in control group. In silico analysis revealed four variations as potentially deleterious, being two in the group with cleft and agenesis and two in the group with cleft without agenesis. CONCLUSION: The study identified novel IFR6 variations in subjects with NSUCLP with or without associated dental agenesis. The hypothesis of a higher frequency of deleterious variations in the subjects with cleft associated with dental agenesis, when compared to the group of cleft without agenesis and control without cleft, was not supported.

Does dental agenesis have an impact on OHRQoL of children, adolescents and young adults? A systematic review.

Dental agenesis (DA) is defined as the congenital absence of teeth and is considered as the most common dental anomaly. It may cause speech and masticatory dysfunctions as well as esthetic problems. Its impact on oral health-related quality of life (OHRQoL) is not fully understood. The aim of the study was to assess whether DA affects OHRQoL of children, adolescents and young adults. A broad search was done on databases (Pubmed, Scopus, Web of Science and Virtual Health Library) using Medical Subject Headings (MeSH) and free terms. Eligibility criteria for article selection were predetermined and were classified according to quality assessment and risk of bias. The electronic search produced 178 titles and abstracts. After excluding duplicate abstracts and applying the eligibility criteria, three articles were assessed for the final qualitative synthesis. The three articles were classified as moderate quality and present risk of bias. No articles were found that had evaluated children and young adults. From the three articles that were selected, only one was found to have a greater impact in the adolescent agenesis group with statistical differences in all domains. There is insufficient evidence available to conclude if DA affects OHRQoL of children, adolescents and young adults.

Missing teeth and pediatric obstructive sleep apnea.

BACKGROUND: Missing teeth in early childhood can result in abnormal facial morphology with narrow upper airway. The potential association between dental agenesis or early dental extractions and the presence of obstructive sleep apnea (OSA) was investigated. METHODS: We reviewed clinical data, results of polysomnographic sleep studies, and orthodontic imaging studies of children with dental agenesis (n = 32) or early extraction of permanent teeth (n = 11) seen during the past 5 years and compared their findings to those of age-, gender-, and body mass index-matched children with normal teeth development but tonsilloadenoid (T&A) hypertrophy and symptoms of OSA (n = 64). RESULTS: The 31 children with dental agenesis and 11 children with early dental extractions had at least 2 permanent teeth missing. All children with missing teeth (n = 43) had clinical complaints and signs evoking OSA. There was a significant difference in mean apnea-hypopnea indices (AHI) in the three dental agenesis, dental extraction, and T&A studied groups (p < 0.001), with mean abnormal AHI lowest in the pediatric dental agenesis group. In the children with missing teeth (n = 43), aging was associated with the presence of a higher AHI (R (2) = 0.71, p < 0.0001). CONCLUSION: Alveolar bone growth is dependent on the presence of the teeth that it supports. The dental agenesis in the studied children was not part of a syndrome and was an isolated finding. Our children with permanent teeth missing due to congenital agenesis or permanent teeth extraction had a smaller oral cavity, known to predispose to the collapse of the upper airway during sleep, and presented with OSA recognized at a later age. Due to the low-grade initial symptomatology, sleep-disordered breathing may be left untreated for a prolonged period with progressive worsening of symptoms over time.

Radiographic Assessment of Dental Maturation in Children With Dental Agenesis.

BACKGROUND: Dental agenesis is the most common developmental anomaly in humans, frequently associated with disorders in dental development and maturation. AIM: The purpose of this study is to determine radiographic variations in dental maturation in a group of Venezuelan children with dental agenesis. STUDY DESIGN: 1,188 panoramic radiographs, from healthy patients ages 5 to 12 years old were studied for agenesis of permanent teeth. Dental maturation was assessed by relative eruption and dental age according to Nolla, comparing children affected with dental agenesis to a stratified control group selected from the same population, excluding children with premature loss of primary teeth in the left quadrants and unclear radiographs. Descriptive analysis, and differences between means and medians (Student t test, Kruskall-Wallis p=0.05) were performed. RESULTS: Medians for Nolla stages were similar between groups, with delay in tooth formation in the agenesis group for second molars (p<0.05) and maxillary lateral incisors and second premolars. Dental age was significantly underestimated for both groups, -0.89 (±0.78) for the control group and -1.20 (±0.95) for the study group. Tooth eruption was similar between groups. CONCLUSION: Dental age was significantly delayed in Venezuelan children with dental agenesis, with variable significance for tooth formation of studied teeth.

Semidirect Restorations in Multidisciplinary Treatment: Viable Option for Children and Teenagers.

Due to the esthetic necessity required nowadays, the multidisciplinary treatment became a fundamental step in the restoration success. When the patient exhibits dental agenesis of one or more elements, he can show difficulty in social interactions. The age of the patient is a limiting factor to esthetic procedures, however, it should be evaluated as a real indicative with each case. The utilization of semi-direct restorations is a viable option due the cost, esthetic and improvement of physical and mechanical properties. The purpose of this paper is to present a case detailing the confection and cementation of anterior semi-direct restorations aimed at an anatomic reestablishment associated with integrated treatment with periodontics and orthodontics.

Maturation of teeth adjacent to dental agenesis site.

OBJECTIVE: The purpose of this study was to evaluate the developmental stage of teeth adjacent to the agenesis site in comparison to their antimeres. MATERIALS AND METHODS: Panoramic views of 39 patients with unilateral dental agenesis and 42 normal controls were evaluated. The dental developmental stage (normal or delayed) of the teeth adjacent to the agenesis site was determined for each patient using the Haavikko's method, while the overall dental age was determined by Becker's method. RESULTS: No statistically significant difference was found in the developmental stage of teeth adjacent to the agenesis, compared to their antimere and to the same teeth in the normal control group. However, the prevalence of cases with no difference in development was almost double for the tooth distal to the agenesis site compared to the tooth mesial to the agenesis site in the hypodontia group (84.6% distal and 43.6% mesial; p < 0.001) and in the control group (83.3% distal and 52.4% mesial; p < 0.002). In most of the cases the tooth distal to the agenesis site was the 1st permanent molar. CONCLUSIONS: (1) No difference was found between the developmental stage of teeth adjacent to the agenesis site and their antimeres. (2) Teeth mesial to the agenesis site showed some delay in development compared to teeth distal to the agenesis site, in this study. (3) The 1st molars, which were in most of the cases the distal adjacent tooth to the site of agenesis, showed developmental stability. (4) Additional longitudinal studies are needed to examine the dental developmental pattern in patients with agenesis.

Prevalence of hypodontia and associated factors: a systematic review and meta-analysis.

OBJECTIVES: To determine the prevalence and factors associated with hypotonia. DESIGN: Systematic review and meta-analysis. DATA SOURCE: A search strategy was developed along with inclusion criteria and run in MEDLINE and EMBASE (published from 2002 to August 2012) databases to reveal all studies on the prevalence of hypodontia or associated factors. A hand search of reference lists and a Google search aimed to improve the sensitivity of the literature search. SELECTION CRITERIA: All studies on the prevalence of hypodontia or associated factors published from 2002 onwards were included. Abstracts of non-English papers were also analyzed. DATA SELECTION AND EXTRACTION: All potential articles were checked against the inclusion criteria independently, and in duplicate by two investigators. A checklist was used to assess the quality of selected studies. MAIN OUTCOME: Prevalence of hypodontia, excluding third molars. RESULTS: The overall prevalence of hypodontia was found to be 6.4% (95% CI: 5.7, 7.2). There was a statistically significant difference in the prevalence of hypodontia by continent (Q = 34.18, P<0.001). Prevalence of hypodontia was the highest in Africa: 13.4% (95% CI: 9.7, 18.0), followed by Europe (7% CI: 6.0-8.0%), Asia (6.3% CI: 4.4, 9.1) and Australia (6.3% CI: 5.3, 7.4) with a lower prevalence in North America (5.0% CI: 4.1-5.9) and Latin America and Caribbean (4.4% CI: 3.2-6.1). Females were found to have a higher prevalence than males (combined OR 1.22; 95% CI: 1.14, 1.30). The most commonly affected teeth were mandibular second premolars followed by maxillary lateral incisors and maxillary second premolars. The prevalence of mild, moderate and severe hypodontia was found to be 81.6, 14.3 and 3.1% respectively. CONCLUSIONS: There was a high variation in the prevalence of hypodontia between the studies. African populations were found to have a higher risk for tooth agenesis and there was an increased risk for females to have hypodontia than males.

Prevalence and Distribution of Dental Anomalies in Schoolchildren in Kuwait.

OBJECTIVE: Dental anomalies (DA) can affect paediatric patients' aesthetics, function, and psychological well-being. There is a lack of data about the prevalence of DA in children in Kuwait. This study aimed to investigate the prevalence and distribution of DA amongst schoolchildren aged 8 to 12 years. METHODS: A retrospective study was conducted using panoramic digital radiographs of children who attended a single dental center. All radiographs were evaluated by 2 calibrated and trained examiners. RESULTS: DA were present in 110 (20.1%) out of the 546 panoramic radiographs examined: 53.6% in females and 46.4% in males. The mean age of children with DA (9.83 ± 1.29) was similar to that of children with no anomalies (9.96 ± 1.46). The most prevalent anomaly was dental agenesis (9.3%), followed by taurodontism (6.6%) and ectopic eruption (EE, 2%). DA were more common in the maxilla (58.2%) compared to the mandible (41.8%, P = .042). Congenitally missing teeth were significantly more frequent in the mandible (56.9%) than in the maxilla (43.1%, P = .003). EE was significantly more common in the maxilla (90.9%) than in the mandible (9.1%, P = .024). Microdontia and root dilacerations were only present in males, whilst supernumerary teeth, transposition, and impacted teeth were noted in females only. CONCLUSIONS: The prevalence of DA amongst schoolchildren in Kuwait was considered to be relatively high. Certain DA were associated with gender. The significant prevalence of DA highlights the need for early diagnosis using panoramic radiographs, particularly during the ages of 9 and 10, in order to ensure effective patient management.

Alveolar morphometry in young adults with and without agenesis of the upper lateral incisor: A retrospective study.

INTRODUCTION: We aimed to compare alveolar morphometry in young adults with agenesis of the upper lateral incisor versus the side without agenesis and versus matched controls. MATERIAL AND METHODS: In this observational retrospective study, cone beam computed tomography scans were obtained of 36 upper hemiarches from young adults aged 15 to 30 years. The hemiarches were distributed into three groups: group 1: 12 upper hemiarches presenting agenesis of the upper lateral incisor; group 2: 12 upper hemiarches from the opposite side without agenesis of the upper lateral incisor (control group 1); and group 3: 12 upper hemiarches without agenesis of the upper lateral incisor matched for age and sex with respect to the affected group (control group 2). A trained and calibrated investigator performed all the alveolar measurements at two different times, including sagittal, coronal and axial slices of each hemiarch. Paired Student's t-tests, Chi-square and repeated measures ANOVA with Bonferroni correction were used, (P<0.05). RESULTS: Apical mesial evaluation of group 1 (4.22±1.19mm) was significantly lower (P<0.001) than that of groups 2 (6.72±1.17mm) and 3 (7.58±1.67mm). Apical distal evaluation also showed differences (P<0.001) among the three groups, with the dimension being smaller in group 1 with agenesis (4.53±1.14mm), followed by group 2 without agenesis (6.23±1.55mm) and the healthy control group 3 (7.73±1.71mm). CONCLUSIONS: Lateral incisor agenesis significantly reduces the alveolar dimensions of the affected area. In cases of unilateral agenesis, the unaffected side also shows sequelae, with decreased dimensions compared to cases without agenesis. This condition should be taken into account when making therapeutic decisions regarding rehabilitation with implants or canine replacement.

Tooth agenesis: An overview of diagnosis, aetiology and management.

Patients with one or more developmentally absent teeth are routinely encountered in dental practice. Tooth agenesis can be associated with significant functional, aesthetic and psycho-social problems. The present article provides an overview of the prevalence and aetiology of tooth agenesis, as well as the condition's clinical characteristics and management options with reference to the evidence base. A timely diagnosis can facilitate the appropriate planning and management which might not be straightforward, and patient care will likely require multi- and inter-disciplinary input. It is critical that dental care practitioners are aware of the clinical characteristics and management options for tooth agenesis.

Chitosan Hydrogel-Delivered ABE8e Corrects PAX9 Mutant in Dental Pulp Stem Cells.

Hypodontia (dental agenesis) is a genetic disorder, and it has been identified that the mutation C175T in PAX9 could lead to hypodontia. Cas9 nickase (nCas9)-mediated homology-directed repair (HDR) and base editing were used for the correction of this mutated point. This study aimed to investigate the effect of HDR and the base editor ABE8e in editing PAX9 mutant. It was found that the chitosan hydrogel was efficient in delivering naked DNA into dental pulp stem cells (DPSCs). To explore the influence of the C175T mutation in PAX9 on the proliferation of DPSCs, hydrogel was employed to deliver PAX9 mutant vector into DPSCs, finding that the PAX9-containing C175T mutation failed to promote the proliferation of DPSCs. Firstly, DPSCs stably carrying PAX9 mutant were constructed. Either an HDR or ABE8e system was delivered into the above-mentioned stable DPSCs, and then the correction efficiency using Sanger sequencing and Western blotting was determined. Meanwhile, the ABE8e presented significantly higher efficiency in correcting C175T compared with HDR. Furthermore, the corrected PAX9 presented enhanced viability and differentiation capacity for osteogenic and neurogenic lineages; the corrected PAX9 even possessed extremely enhanced transcriptional activation ability. In summary, this study has powerful implications for studies into base editors, chitosan hydrogel, and DPSCs in treating hypodontia.

Radiographic evaluation of non-syndromic third molar agenesis in two Mediterranean populations.

BACKGROUND AND AIMS: Third molar agenesis is a common finding across the world. Many studies have assessed third molar agenesis in different ethnicities and populations. However, there are no such studies in the Italian and Lebanese populations. Our study aims to evaluate the prevalence of third molar agenesis and study the pattern and distribution of agenesis in between genders in Italian and Lebanese Mediterranean populations and compare these findings with other global and Mediterranean populations' studies. METHODS: Retrospective chart review was conducted based on the history and orthopantomograms of adolescents aged 12 to 21 years to assess the agenesis of third molars in a sample of Italian and Lebanese populations by two experienced dental surgeons twice within 1 month. Descriptive and comparative tests were used to analyze the patterns of ageneses and make comparisons between the two samples. RESULTS: 23.4% of the studied sample had at least one third molar agenesis; females were more likely to have two or more third molar agenesis than males, but neither sex predisposition for single third-molar agenesis was recorded. Both the Italian and Lebanese subgroups seemed to have similar results. The maxillary right third molar was the most common third molar to be absent. Two or more ageneses were more common than one third molar agenesis. CONCLUSION: Our Mediterranean population results fall within the range reported in the literature and corroborate with the global average prevalence.