A Pathogenetic Model for the Origins and Locations of Idiopathic Supernumerary Teeth

The Journal of Anatomy A Pathogenetic Model For The Origins And Loca - tions Of Idiopathic Supernumerary Teeth. *Corresponding Author: Mark Lubinsky, 6003 W. Washington Blvd, Wauwatosa, WI 53213, Germany, Tel: (414) 702-9579. Email: [email protected] Received: 06-May-2025, Manuscript No. TJOA-4848 ; Editor Assigned: 09-May-2025 ; Reviewed: 21-May-2025, QC No. TJOA-4848 ; Published: 03-Jun-2025, DOI: 10.52338/tjoa.2025.4848 Citation: Mark Lubinsky. A Pathogenetic Model for the Origins and Locations of Idiopathic Supernumerary Teeth. The Journal of Anatomy. 2025 June; 11(1). doi: 10.52338/tjoa.2025.4848. Copyright © 2025 Mark Lubinsky. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ISSN 2995-6552 Research Article Mark Lubinsky, M.D. (orcid.org/0000-0002-6788-6876) Running head: Pathogenesis of Supernumerary Teeth www.directivepublications.org Abstract The origins and localizations of idiopathic supernumerary teeth are much debated. However, idiopathic supernumeraries can be explained by a combination of localized anterior premaxillary factors and a general dental lamina effect that may also involve normal teeth. Midface Sonic hedgehog (SHH) signaling induces mesiodentes and tuberculate incisors, potentiated by midline developmental weaknesses and genetic variants. SHH can affect morphology, with complex tuberculates from longer primary dentition exposures, but simpler secondary mesiodentes with crown inversions and palatal placements that reflect gradients. Such local factors are minimized with multiple supernumeraries (5 or more), showing other effects more clearly. Here, laminal layer growth differences cause inductive morphogen “sinks” through buckling at stress points, which is greatest at mid-lamina and least at the ends, and increasing with length. Dental lamina sectional differences in these parameters explain more mandibular than maxillary multiples, relatively few incisors, premolars as commonest in the lower jaw, and molars in the upper. Terminal laminal buckling with supplemental teeth at the end of incisor and molar series is unexpected, but teeth develop as groups, and a correctly oriented supernumerary may develop normally and displace a series, while end position vulnerabilities cause distortions of an otherwise normal tooth. Keywords : Buckling; dental lamina; premaxilla; Sonic hedgehog; supernumerary teeth. INTRODUCTION Supernumerary teeth (ST) are the most common human malformations, with likely rates of 2.4- 6%, “or possibly even higher.” 1

Although causally heterogeneous, with some genetic forms, 2 most are idiopathic without other findings, highly variable, and can be categorized by numbers, location, morphology, and other factors. 3

Here, a dual pathogenic model for idiopathic ST is presented with 1. A general mechanism involving the entire dentition as mechanical stress related dental lamina buckling gives disruptions that create a focus for tooth initiation (Figure 1). This may also influence normal tooth induction. 2. Localized premaxillary effects with midface induction by Sonic hedgehog (SHH) 4 and a specific midline vulnerability. 5,6 Figure 1. Buckling and tooth bud initiation. o = new tooth bud in disrupted area.

Directive Publications Mark Lubinsky These mechanisms explain multiple observations of ST, including male biases, 7 frequent mesiodental crown inversions and palatal placement,8 more multiples in the mandible, relatively few in the incisors, premolars as the most common in the lower jaw, and molars as the most common in the upper. 9,10,11 MATERIALS AND METHODS Literature review analysis limited to idiopathic ST without facial clefts, syndromes, or a positive family history. Wisdom teeth and odontoma are excluded. As few as 2 ST have been labeled multiples, 12,13 but 5 or more are typically cited, a confusing designation with up to four teeth defined as isolated! However, this is entrenched in the literature and, for consistency, this cutoff and isolated and multiple are used in this sense here. Premaxillary ST include three standard types (Table 1), with great morphological variability: Mesiodens can be tuberculate in form, tuberculates can be conical, and supplementals can be of both shapes as well as normal. 14 Table 1. Types of isolated premaxillary ST. After Garvey et al. 15 . Type Typical Morphology Typical Location Dentition Mesiodens Conical. Pairs common Between central incisors palatal and inverted Secondary Tuberculate > one cusp or tubercle, Barrel- shaped. palatal aspect of central incisors Primary Supplemental Duplication in normal series end of a tooth series, esp, maxillary lateral incisorSecondary SUPERNUMERARY CHARACTERISTICS Epidemiologies vary, reflecting methodological considerations and population differences. Radiographs are needed to detect unerupted examples, and rates vary with age, 3 with ST about three times more common in permanent dentition. New ST can appear for decades, 9 and mesiodentes, the most common type, may be resorbed over time. 16 Panoramic radiographs showed ST frequencies of 1.2- 3%, and data suggested 2.4-6%, “or possibly even higher.” 1 With this, statistics need to be regarded as rough estimates highly dependent upon context. Most ST are single, and frequencies rapidly decrease as numbers rise: Rajab and Hamdan 17 noted one extra tooth in 77% of cases, 2 in 18·4%, and 3 or more in 4·6%, while Açikgöz et al. 18 found only 0.06% with 5 or more. Mesiodentes, typically the most common type (although not in the series of Brinkmann et al. 19 ), are exceptional with multiples, and premaxillary ST predominate with 4 or less: In large series (over 100 patients) Herath et al. 20 found 94.94% of ST in the premaxilla, De Oliveira Gomes et al. 21 86.7%, and Rajab and Hamdan 17 90% (92·8% of these in the central incisor region). While most multiples were mandibular, 95% of patients with multiples had ST in both jaws, 9,10,11 supporting a generalized process instead of localized effects with isolated supernumeraries. BUCKLING AND INITIATION Biologically, buckling, an acute structural deformation from mechanical stress, arises from growth differentials in adherent tissue layers, creating structures such as intestinal loops and cerebral cortex convolutions. There can be secondary effects- gut constraints on epithelial growth cause villus morphogenesis, and also localize stem cells to crypts as “undulations create sinks for morphogens that are secreted by the epithelial cells, leading to a concentration gradient along the length of the villus. So... constrained growth of the epithelium not only directs its morphogenesis but also its pattern of differentiation.” 22

And here, aberrant buckling of the dental lamina, the source of normal tooth buds, may create similar morphogenic field distortions 23 capable of initiating extra teeth. The lamina originates in five separate areas (Figure 2). Epithelial invaginations into mesenchyme 24 form two adherent linear layers where complex interactions affect tooth size, number, and morphology. 25 Different molecular signals in the two layers 26

indicate possibilities for different growth rates primed for buckling. 22 At the same time, disruption of the dental lamina can induce additional teeth, as with oral clefts. 27

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Mark Lubinsky Directive Publications Figure 2. Dental laminae relative sizes and locations (not to scale). Page - 3Open Access, Volume 11 , 2025 Other factors being equal, mechanical stress is greatest at the middle of a structure and least at the ends, and increases with length. 22 Local variations and inhomogeneities can modify this, and lateral asymmetries could produce labial or palatal displacements. U-shaped buckling is also consistent with rosettes, “a classical clustered flower like presentation” 9

(Figure 1). More mesenchyme increases tooth numbers, 25 so a shorter lamina should show fewer and smaller teeth, and longer more and larger. And here, 27 suggested human tooth size as a normally distributed genetic trait correlates with most number variations, larger with extra, and smaller with missing, teeth. Male teeth tend to be larger, and ST biased, as seen with mesiodentes, 28,29 anterior maxillaries, 30 premolars, 31 and multiple ST (below), but absences tend to be female. 32

Dental lamina buckling can include later effects as well. With mesenchymal invagination, the epithelial bud forms a folded cap, where a model of buckling from differential growth of adherent layers can explain cap shape, with specific parameters determining the number of invaginations. 33 After this, Osborn 34 noted how “Cells at the growing soft tissue interface between the ectoderm and mesoderm in a tooth anlage are observed to buckle and fold into a template for the shape of the tooth crown.” A computer model based upon directional constraints that “force the growing epithelium to buckle and fold” could generate the number and shape of tooth crown cusps, and explain evolutionary changes. Marin- Riera et al. 35 further extend these approaches. With this, factors enhancing laminal buckling could affect tooth number and morphology together, with simple conical and complex tuberculate morphologies as opposite ends of a spectrum of fine scale laminal responses associated with grosser effects on tooth initiation (below). Human teeth are also usually symmetrical, often remarkably so: In a cone-beam computed tomography study, for the first and second molars in both jaws, the root and canal morphology of specific teeth “showed perfect symmetry” in over 70% of cases when both were present. 36 With this, and a generalized mechanism (above), bilaterally symmetrical ST are not unexpected. Finally, buckling mechanics should interact with molecular tooth initiation. SHH involvement is noted in the next section, but other genes implicated with syndromic supernumeraries2 may also affect buckling through differential growth effects. THE PREMAXILLA While buckling can occur throughout the dentition, unique premaxillary factors also affect isolated ST. Mesiodentes, generally the most common ST type, are limited to the central maxillary incisor gap, and reflect several factors. First, there is SHH midface induction. Here, “Pathway activity is detected in the medial nasal processes that contribute to the median aspect of the upper lip and primary palate, as well as the maxillary processes that give rise to the lateral aspects of the upper lip and the secondary palate.” 37 Anatomically, the upper incisors are all adjacent to the premaxilla, paired bones fused anteriorally, with an incisive fossa posteriorly. They are also adjacent to the median palatine process/primary palate. Therefore, for teeth, the maxillary incisors are associated with the highest concentrations of SHH and should be particularly vulnerable to variations in levels. Premaxillary effects from deleterious mutations correlate with incisor morphology, ranging from a single central incisor with minor changes, to total absence with agenesis, while canines arise from separate fields 27 and are unaffected. Asymmetric signaling from the palatal side of the lamina would explain certain positional distortions: Radiographically, mesiodentes crowns were inverted in 67%, horizontal to the tooth axis in 6%, and normally directed in only 27%, while 89% were palatal against the dental arch, 11% overlapped the arch, and none were labial. 8

Second, major contributions to mesiodentes from cooperative interactions between co-occurring genetic alterations, including “functionally enriched gene groups in the sonic

Mark Lubinsky Directive Publications hedgehog... signaling pathways.” 38 This could explain the rarity of mesiodentes with multiple ST, since those genes would be independently occurring factors. At the same time, although numbers are small, high mesiodentes rates with familial multiple ST (“Multiple ST Analysis: Methods,” below) may reflect a more general molecular defect that affects other areas of dentition as well. Third, a particular midline vulnerability to developmental disturbances 5 should create a susceptible area between the anterior maxillary incisors. This reflects midline topology as a null space between two mirror image developmental fields, resulting in the loss of positional information central to cell fate determination. 6 This should be exaggerated by midline widening and, in fact, mesiodentes are associated with diastemata, broadened spaces between the central incisors. 39 Diastemata with or without mesiodentes with the Nance-Horan syndrome, 40

and frequent mesiodentes in Opitz G/BBB syndrome, 3 which involves midline widening, show that the gaps are not simply caused by the supernumeraries. Buckling is also most likely at the middle of dental laminae which, for the premaxilla, is at the central incisor gap. The last two vulnerabilities are absent in the mandible, which lacks a middle lamina (Figure 2). Without a similar relationship to SHH induction. it bears a very different relationship to the midline, implying a considerably reduced risk for extra teeth, which is indeed the case. (Incidentally, suggestions of mesiodentes as a holoprosencephaly microform rest upon one mother with mesiodens and an affected child with no detectable mutation. 42

This seems unlikely, with a dearth of reports of this common dental finding in mutation carriers, while midline narrowing with holoprosencephaly should actually decrease rates.) Another type of ST, tuberculates, are on the palatal aspect of central incisors, with more than one cusp or tubercle, generally barrel-shaped, often paired, and sometimes invaginated. 15 Clustering around the midline suggests buckling, but associated diastemata seem to be absent, going against positional information effects. However, palatal placement supports midface SHH inductive effects. Differences from mesiodentes may reflect timing: simple conical mesiodentes are in the secondary dentition, while tuberculates are primary, giving a longer/stronger exposure to SHH signaling for a more complex structure. Finally, supplemental duplications at the end of a tooth series may be morphologically normal. They are most common at the maxillary lateral incisor, again consistent with SHH effects here, but also appear elsewhere, as with distomolars at the end of the molar series. Buckling in both locations should be unlikely at the ends of lamina segments, but apparent aberrancies may be illusory. Tooth series develop as coordinated units. In both Butler’s field theory and the clonal theory, the two main suggested mechanisms, the same teeth are more stable in development, and the first upper incisors, second lower incisors, canines and first molars show the least amount of variation. 43 With this, the supplemental tooth at the end of a series may not be the actual supernumerary. That is, if an additional tooth is induced in normal alignment, as between the first and second molars, the developmental process will normalize it morphologically, giving a second molar, and laterally displacing subsequent teeth. With this, the most distal molar in the new series is probably the most sensitive to abnormal development, and most likely to be atypically shaped. 44 PREDICTIONS AND EXPLANATIONS The buckling hypothesis can explain a variety of observations, with specific predictions that can be tested against multiples generally unobscured by premaxillary factors: 1. With equal total lamina length, two longer segments in the mandible compared to shorter triplets in the maxilla mean more ST in the mandible. 2. A short lamina in the maxilla, and a mandibular location at an end of a laminal segment, would explain relatively fewer ST incisors. 3. Premolars at the mandibular laminae centers should be the most common ST in the lower jaw. 4. The center shifts with shorter lateral maxillary laminae, making molars most likely in the upper jaw. 5. Males, with longer laminae, 32 should have more multiples than females. Buckling can also explain some more general observations: 6. Longer laminae in the secondary dentition should mean more ST than in the primary. 7. Asymmetries perpendicular to the lamina should produce labial or palatal displacements, 8. Buckling variations can explain certain binaries and rosettes (Figure 1) MULTIPLE ST ANALYSIS: METHODS To test the above predictions, and better understand multiple ST epidemiology, cases were analyzed from three recent multiple ST reviews. 9,10,11 Criteria and definitions differed, and overlaps were common, but each study had unique cases. We used five as a minimal ST number, and excluded: 1.With a continuously hyperactive dental lamina, 9 as atypical; 2. An outlier with 22 ST, 45 the only instance of more than 17 in all; 3. Familial cases. 46,47,48 These are rare, 49 and probably heterogeneous. 4. A patient with more than the 6 maxillary ST50 that others cite, but without clear details. With this, 58 cases remained. Page - 4Open Access, Volume 11 , 2025

Mark Lubinsky Directive Publications Some caveats: Again, figures should be regarded as estimates. Besides methodological and epidemiological issues, multiples are diverse, and local factors affect differentiation. Criteria vary, and segment based classifications blur premaxillary distinctions from nearby areas. To allow for this, superior canines with premaxillary findings are included as anterior. This introduces some inaccuracy, but canine ST are relatively infrequent with multiples, minimizing effects. Frequencies also have two different contexts with different causal implications: ST numbers, and patient rates; e.g, anteriors as 12% of ST, but 37% of patients. There are also ascertainment and publication biases: More ST have increased dental problems, and are more impressive as case reports. As evidence, 25 out of 38 individual reports had more than 8 ST compared to only 3 out of 19 patients where several cases were reported together (see below). MULTIPLE ST FINDINGS OF THE 58 CASES ANALYZED 1. There were 41 males and 15 females, plus 3 unspecified, for a 2.7:1 ratio. 2. Confirming separation from other multiples, mesiodentes were rare, with two solitary, and one quadruple in only three patients, which may be coincidental,. However, three solitary mesiodentes were seen in the five excluded familial cases, and all affected patients with mesiodentes in the excluded and included groups had more than ten ST, so some relationship with multiples is possible. 3. Both jaws had ST in all except 2 patients with maxillary findings only. 4. There were 233 maxillary and 290 mandibular ST. Excluding the 6 mesiodentes, 65 were anterior, with about as many in each jaw. Non-anterior ST were roughly 45% maxillary and 55% mandibular. 5. Anterior involvement (typically, without mesiodentes) in one or both jaws occurred in 32 patients (39%), who had about 12% of all supernumeraries by number. 6. There were roughly 82 molars and distomolars in 27 patients, the former about twice as common numerically, and perhaps a bit more common in terms of numbers of patients. 7. Canine involvement was obscured by consolidations with other groups, but seemed uncommon, and probably less frequent than distomolars. 8. Premolars were more common in the mandible, molars in the maxilla. 9. Isolated and multiple findings differed radically for the premaxilla: Mesiodentes, with the highest isolated rate, become the rarest, and the percentage of other incisor ST was about one fifth of the isolated rate. This supports differentiation of the premaxillary area from the rest of the dentition. These findings confirm buckling predictions, and support a generalized process separate from the localized premaxillary factors involved with isolated ST. ALTERNATIVE EXPLANATIONS OTHER SUGGESTED EXPLANATIONS FOR ST SEEM WANTING 1. There is considerable evidence against atavisms, reversions to ancestral dental formulae with more teeth. 1 2. Documentation of tooth bud splitting, with or without to local trauma, is scanty at best, and fails to explain observed patterns. 1 3. Environmental factors could explain population differences, but no patterns or indications of specific factors have been noted. 4. Population variations may play a role, as in a Spanish series 19 where mesiodentes were not the most common ST. 5. Single gene inheritance is doubtful. Although ST are common, familial cases are generally few (although this can occur in specific populations) 41 and findings of a single ST in two family members 1 may be coincidental, given general frequencies. 6. Hyperactivity of the dental lamina occurs in some situations, 9 but specific implications are wanting. 7. While a molecular etiology has been suggested, details are vague. 41 Certainly specific mutations cause ST, but no one gene is responsible, 2 and pathogenetic contributions, as with SHH, differ from a primary general cause. These proposals treat ST as a single entity with a single explanation, and fail to explain localizations or to differentiate mesiodentes from other ST. There is sufficient evidence for causal heterogeneity to reject such approaches, and the factors suggested here explain a far wider range of observations than any of these alternatives. QUESTIONS THE SUGGESTED MECHANISMS LEAVE SEVERAL QUESTIONS OPEN, INCLUDING 1. Do buckling effects on ST throughout the dentition suggest a role in normal initiation? This could involve localized areas of weakness related to normal structural or molecular inhomogeneities. 2. Do similar mechanical issues apply to hypodontia (although racial differences in commonest affected teeth45 suggest added levels of complexity here)? 3. Even though syndromic supernumeraries 2 show that Mendelian molecular processes can be involved, it is uncertain why non-syndromic familial multiples are so rare. 4. While mechanical effects on morphogenic fields similar to that suggested for intestinal crypts 23 are plausible, the Page - 5Open Access, Volume 11 , 2025

Mark Lubinsky Directive Publications relationships of specific molecular genes and mutations to buckling need to be elucidated. CONCLUSIONS The most common ST are premaxillary, where unique causative factors include a midline vulnerability accentuated by broadening of the area, as with diastemata, and absent in the mandible. Multifactorial effects from genetic variants also contribute, while SHH signaling related to midface induction is of particular importance, and promotes palatal locations. It may affect ST morphology, with more complex tuberculates in the primary dentition, and simpler conicals in the secondary. There are also contributions from dental lamina buckling. Growth differences in adherent layers of the lamina can also cause ST formation from buckling throughout the dentition. Mechanical factors control stress, with the greatest at the middle, least at the ends, and increases with greater lamina length. Effects are clearest with multiple (5 or more) ST, where premaxillary factors are minimized, and explain multiple ST predominance in the mandible, with mostly premolars, mostly upper jaw molars, and relatively few incisors. Contributions to normal tooth initiation are also possible. Methodological and epidemiological issues affect assessments, and reports are often incomplete. Tooth groups need to be separated, numbers of patients with specific findings included, and details on individual teeth with multiples provided. Although numbers are small, excess mesiodentes with familial ST suggest different pathogenetic processes with non-syndromic Mendelian forms. Acknowledgments I am grateful to Dr. Piranit Kantaputra for his support, insights, and suggestions. There was no grant support and there are no conflicts of interest. As the sole author, I contributed everything in the paper. REFERENCES 1. Anthonappa RP, King NM, Rabie AB. Prevalence of supernumerary teeth based on panoramic radiographs revisited. Pediatr Dent 2013 35:257-261. 2. Lubinsky M, Kantaputra PN. Syndromes with supernumerary teeth. Am J Med Genet 2016 170A: 2611-2616. 3. Mallineni SK, Nuvvula S, Cheung ACH. A comprehensive review of the literature and data analysis on hypo- hyperdontia. J Oral Sci 2014 56:295-302. 4. Muenke M, Beachy PA. Genetics of ventral forebrain development and holoprosencephaly. Curr Opin Genet Dev 2000 10:262-269. 5. Opitz JM, Gilbert EF. CNS anomalies and the midline as a “developmental field.” Am J Med Genet 1982 12:443- 455. 6. Lubinsky MS. Midline developmental “weakness” as a consequence of determinative field properties.. Am J Med Genet 1987 28(S3):23-28. 7. Ata-Ali F, Ata-Ali J, Peñarrocha-Oltra D, Peñarrocha- Diago M. Prevalence, etiology, diagnosis, treatment and complications of supernumerary teeth. J Clin Exper Dent 2014 6(4):e414. 8. Asaumi JI, Shibata Y, Yanagi Y, Hisatomi M, Matsuzaki H, Konouchi H, Kishi K. Radiographic examination of mesiodens and their associated complications. Dentomaxillofac Radiol 2004 33:125-127. 9. Gupta A, Nagar P, Khandeparker RV, Munjal D, Sethi HS. 2015. Hyperactive dental lamina in a 24-year-old female - a case report and review of literature. J Clin Diagn Res 9:ZE01-4. doi: 10.7860/JCDR/2015/14671.6356. 10. Thumati P, David CM, Tiwari R. Non-syndromic multiple supernumerary teeth: a case report and review of literature. IJSS Case Rep Rev 2014. 1:1-5. 11. Alvira-González J, Gay-Escoda C. 2012. Non-syndromic multiple supernumerary teeth: meta-analysis. J Oral Pathol Med 41:361-366. 12. Fernández Montenegro P, Valmaseda Castellón E, Berini Aytés L, Gay Escoda C.Estudio retrospectivo de 145 dientes supernumerarios. Med Oral Patol Oral Cir Bucal 2006 11:E339-344. 13. Hyun HK, Lee SJ, Ahn BD, Lee ZH, Heo MS, Seo BM, Kim JW. Nonsyndromic multiple mandibular supernumerary premolars. J Oral Maxillofac Surg 2008 66:1366-1369. 14. Mossaz J, Kloukos D, Pandis N, Suter VG, Katsaros C, Bornstein MM. Morphologic characteristics, location, and associated complications of maxillary and mandibular supernumerary teeth as evaluated using cone beam computed tomography. Eur J Orthod 2014 36:708-718. Page - 6Open Access, Volume 11 , 2025

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Mark Lubinsky Directive Publications maxillary and mandibular molars in a white population: a cone-beam computed tomography study in vivo. J Endod 2013 39:1545-1548. 37. Heyne GW, Melberg CG, Doroodchi P, Parins KF, Kietzman HW, Everson JL, Ansen-Wilson LJ, Lipinski RJ. Definition of Critical Periods for Hedgehog Pathway Antagonist-Induced Holoprosencephaly, Cleft Lip, and Cleft Palate. PloS one 2015 10(3):e0120517. 38. Kim YY, Hwang J, Kim HS, Kwon HJ, Kim S, Lee JH, Lee JH.Genetic alterations in mesiodens as revealed by targeted NGS and gene co-occurrence network analysis. Oral Dis 2017 23:966-972. 39. Santosh P, Pachori Y, Sumita K, Khandelwal S, Likhyani L, Maheshwari S. Frequency of mesiodens in the pediatric population in North India: A radiographic study. J Clin Exp Dent 2013. 5: e223–e226. doi: 10.4317/jced.51162 40. Walpole IR, Hockey A, Nicoll A. The Nance-Horan syndrome. J Med Genetics 1990 27:632-634. 41. McBeain M, Miloro M Characteristics of supernumerary teeth in nonsyndromic population in an urban dental school setting. J Oral Maxillofac Surg 2017 pii: S0278- 2391(17)31283-1. doi: 10.1016/j.joms.2017.10.013. 41. Lu X, Yu F, Liu J, Cai W, Zhao Y, Zhao S, Liu S. The epidemiology of supernumerary teeth and the associated molecular mechanism. Organogenesis 2017 13:71-82. 42. Chan MY, Shifteh K, Shanske AL.. Mesiodens, a new microform of holoprosencephaly? Am J Med Genet 2009 149A:268-271. 43. Luna LH. Interpretative potential of dental metrics for biodistance analysis in hunter-gatherers from central Argentina. A theoretical-methodological approach. HOMO - J Comparat Hum Biol 2015 66:432–447. 44. Chen L, Liversidge H, Chen K, Farella M, Sassani S, Patel D, Al-Ani Az, Brook A. Delay in dental development and variations in root morphology are outcomes of the complex adaptive system associated with the numerical variation of hypodontia. Int J Design Nat Ecodynamics 2018 13:101-106. 44. Larmour CJ, Mossey PA, Thind BS, Forgie AH, Stirrups DR, Colin J. Hypodontia–a retrospective review of prevalence and etiology. Part I. Quintessence Int 2005 36:263-270. 45. Rizutti N, Scotti S. 1997. A case of hyperdontia with twenty two supernumeraries: Its surgical-orthodontic treatment. Am J Orthod Dentofacial Orthop 111:471– 480. 46. Batra P, Duggal R, Parkash H. Non-syndromic multiple supernumerary teeth transmitted as an autosomal dominant trait. J Oral Pathol Med 2005 34:621–625. 47. Desai RS, Shah NP.Multiple supernumerary teeth in two brothers: a case report. 1998 J Oral Pathol Med 27:411– 413. 48. Mercuri LG, O’Neill R. Multiple impacted supernumerary teeth. Oral Surg Oral Med Oral Pathol 1980 50:293. 49. Orhan AI, Özer L, Orhan K. Familial occurrence of nonsyndromal multiple supernumerary teeth: a rare condition. Angle Orthod 2006 76:891-897. 50. Rosenthaler H, Beideman RW. Multiple supernumerary teeth. Oral Surg Oral Med Oral Pathol 1983 56: 227. Page - 8Open Access, Volume 11 , 2025

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