Maxillary first molar agenesis and other dental anomalies

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1 Originl Article Mxillry first molr genesis nd other dentl nomlies Ryot Abe ; Toshiy Endo b ; Shohchi Shimook c ABSTRACT Objective: To explore the ssocition of mxillry first molr genesis with other dentl nomlies in Jpnese orthodontic ptients. Mterils nd Methods: A totl of 32 subjects with one or two congenitlly missing mxillry first molrs (group M) were selected nd divided into group 1M (12 subjects with one mxillry first molr missing) nd group 2M (20 subjects with two mxillry first molrs missing). As controls, 32 sex-mtched subjects without genesis of mxillry first molrs were collected (group C). Pnormic nd peripicl rdiogrphs, cephlogrms, study models, introrl photogrphs, nd nmnestic dt were used to identify nomlies of permnent teeth. Chi-squre, Fisher s exct, Kruskl-Wllis, nd Steel-Dwss tests were used to mke sttisticl comprisons. Results: The prevlence rtes of tooth genesis other thn the mxillry first molrs nd dvnced tooth genesis, with third molrs excluded, were significntly higher in group 2M thn in group C. The bsence of second premolrs ws most common. The prevlence rte of third molr genesis ws significntly higher in groups 1M nd 2M thn in group C. The occurrence of symmetricl genesis of the mndibulr third molrs ws prticulrly notble in group 2M s compred to group 1M, in which mxillry third molr genesis ws predominnt. There ws no significnt ssocition between mxillry first molr genesis nd other dentl nomlies, except for genesis of teeth other thn mxillry first molrs. Conclusion: Agenesis of mxillry first molrs is ssocited with higher prevlence of other permnent tooth genesis nd dvnced tooth genesis. (Angle Orthod. 2010;80: ) KEY WORDS: Mxillry first molr genesis; Third molr genesis; Advnced tooth genesis; Dentl nomly INTRODUCTION Agenesis of mxillry first molrs does not occur frequently in generl nd orthodontic popultions. 1 The reported prevlence rte of mxillry first molr genesis ws 2.9% of the totl number of missing teeth in generl popultion 1 nd hs been reported to vry from 0.4% 2 to 4% 3 in orthodontic ptients. Mxillry first molr genesis ccounts for bout 0.5% of orthodontic ptients with tooth genesis. 2 Despite the low prevlence rte, mxillry first molr genesis presents cliniclly significnt problems ffecting tretment plnning nd outcome, becuse first molrs ply n importnt role in the mstiction of food, in supporting the verticl dimension of the fce, nd s nchorge teeth ginst orthodontic forces. Subjects with mxillry first molr genesis showed more remrkble skeletl nd dentl devitions thn those without genesis of this clss of tooth. 4 Some studies show tht the prevlence of mxillry first molr genesis is reltively high in orthodontic ptients with dvnced tooth genesis. 1,3,5 The prevlence rtes of mxillry first molr genesis re 4% nd 9.2% in Jpnese orthodontic popultions with tooth genesis nd dvnced tooth genesis, respectively. 3,5 These rtes re higher thn those reported in previous studies deling with other ethnic groups, 1,2,6 thus suggesting tht the mxillry first molrs re more commonly missing in Jpnese people. Severl studies hve reported n ssocition between tooth genesis nd other dentl nom Assistnt Professor, Orthodontic Dentistry, The Nippon Dentl University Niigt Hospitl, Niigt, Jpn. b Professor nd Chirmn, Orthodontic Dentistry, The Nippon Dentl University Niigt Hospitl, Niigt, Jpn. c Professor nd Chirmn, Deprtment of Peditric Dentistry, The Nippon Dentl University School of Life Dentistry t Niigt, Niigt, Jpn. Corresponding uthor: Dr Toshiy Endo, Professor nd Chirmn, Orthodontic Dentistry, The Nippon Dentl University Niigt Hospitl, 1-8 Hmur-cho, Chuo-ku, Niigt , Jpn (e-mil: endoto@ngt.ndu.c.jp) Accepted: Mrch Submitted: Jnury G 2010 by The EH Angle Eduction nd Reserch Foundtion, Inc DOI: /

2 MAXILLARY FIRST MOLAR AGENESIS 1003 Tble 1. Numbers nd Men Ages (Stndrd Devition) of Subjects t Registrtion Group 1M Group 2M Group M Group C Number of subjects Age 10 y (1 y 10 mo) 13 y 6 mo (4 y 2 mo) 12 y (4 y 1 mo) 8 y 10 mo (1 y 6 mo) lies. 1,2,6,7 Grib et l. 7 sttisticlly evluted the prevlence of other dentl nomlies in orthodontic ptients with second premolr genesis nd provided evidence tht genesis of other permnent teeth, microdonti, deciduous molr infrocclusion, nd certin dentl ectopis re the products of the sme genetic mechnisms tht cuse second premolr genesis. Grn nd Lewis 8 reported tht third molr genesis ws significntly ssocited with genesis of lterl incisors nd second premolrs. No literture on the ssocition of mxillry first molr genesis with other dentl nomlies ws found in PubMed serch. Severl studies hve furnished sufficient evidence tht genes ply criticl role in the etiology of tooth genesis. 6,9,10 Grhnen 6 stted tht in sibling reltionships in which the ptients or the prents hd six or more missing teeth, the penetrnce ppered to hve been high, thus supporting the hypothesis tht tooth genesis is geneticlly determined. Vstrdis et l. 9 reported tht MSX1 homeodomin missense muttion cused selective genesis of the second premolrs nd third molrs in n Americn fmily with severe form of utosoml-dominnt tooth genesis. Stockton et l. 10 ssocited frmeshift muttion in PAX9 with utosoml-dominnt oligodonti, which involved the bsence of most permnent molrs. The purpose of the present study ws to explore the ssocition of mxillry first molr genesis with other dentl nomlies in Jpnese orthodontic ptients. MATERIALS AND METHODS A totl of 32 Jpnese subjects with one or two congenitlly missing mxillry first molrs (the genesis group, Group M) were selected from the files of orthodontic ptients who hd visited the orthodontic clinic t Nippon Dentl University Niigt Hospitl. The group comprised 7 mle nd 25 femle ptients. On the first visit, ech subject ws given registrtion number. Where mxillry first molr genesis ws found, the djcent number of the sme sex ws included in control group (Group C). Group M ws further divided into two groups. One group consisted of 12 subjects (4 mle nd 8 femle) with genesis of one mxillry first molr (Group 1M), nd the other ws mde up of 20 subjects (3 mle nd 17 femle) with genesis of both mxillry first molrs (Group 2M). Group 1M comprised seven subjects with genesis of the mxillry right first molr nd five with genesis of the mxillry left first molr. The number nd men ges of the subjects in ech group t the time of registrtion re shown in Tble 1. Subjects who hd such developmentl nomlies s ectoderml dysplsi or cleft lip nd/or plte or who hd undergone orthodontic tretment were excluded from this study. Pnormic nd peripicl rdiogrphs, lterl cephlogrms, study models, introrl photogrphs, nd nmnestic dt were used to identify the dentl nomlies of permnent teeth in number, shpe, nd position (see Tble 2). The dentl nomlies were exmined by single investigtor. Anomlies in Number Tooth genesis ws exmined minly using longitudinl pnormic rdiogrphs, which were vilble for most ptients receiving orthodontic tretments. A tooth ws dignosed s presenting genesis when no minerliztion of the tooth crown could be identified on the pnormic rdiogrphs nd when no evidence of its hving been extrcted ws recognized. The study models nd nmnestic dt were used s reference mterils to prevent wrong dignoses. To exclude ny cses of lte minerlized teeth, pnormic rdiogrphic exmintions were performed only on subjects who were t lest 14 yers old. This criticl ge ws dopted following the suggestions of Grn nd Lewis 8 tht third molr genesis could not be confirmed in ptients under 14 yers of ge. Third molrs were included in this study. Agenesis of the mxillry first molrs ws dignosed when the most nterior mxillry molrs looked more like mxillry second molrs thn mxillry first molrs in crown morphology nd root development nd erupted t the ge of 9 to 10 yers, nd when only one or two molrs were identified in the ffected qudrnts. 1,5 Supernumerry teeth nd mesiodentes were dignosed on the pnormic rdiogrphs. Anomlies in Shpe The occlusl surfce morphology of mxillry first nd second molrs tht hd erupted ws evluted on study models in ech group ccording to the clssifiction of Dhlberg. 11 The occlusl surfce ptterns were divided into four clsses ccording to the number nd size of the cusps (Figure 1). Fused, concrescent, nd geminted teeth were determined using peripicl rdiogrphs nd study

3 1004 ABE, ENDO, SHIMOOKA Tble 2. Numbers nd Percentges of Subjects with Different Anomlies nd Sttisticl Comprisons Group 1M (N 5 12) Group 2M (N 5 20) Group M Group C Chi-Squre Test or Fisher s Exct Test/P Vlue 1M vs 2M 1M vs C 2M vs C M vs C Anomlies of number Tooth genesis (excluding third molrs) 2 (16.7) 8 (40.0) 10 (31.3) 2 (6.3) **.010* Mxillry lterl genesis 0 (0.0) 3 (15.0) 3 (9.4) 0 (0.0) Second premolr genesis 2 (16.7) 7 (35.0) 9 (28.1) 2 (6.3) *.020* Symmetricl tooth genesis 0 (0.0) 8 (40.0) 8 (40.0) 1 (3.1).014* ***.026* Third molr genesis 9 (75.0) 13 (65.0) 22 (68.8) 7 (21.9) **.002**.000*** Supernumerry tooth (excluding mesiodens) 0 (0.0) 2 (10.0) 2 (6.3) 1 (3.1) Mesiodens 1 (8.3) 0 (0.0) 1 (3.1) 1 (3.1) Anomlies of shpe Fused tooth 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Concrescent tooth 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Geminted tooth 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Peg-shped lterl incisor 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.1) Shovel-shped incisor 0 (0.0) 2 (10.0) 2 (6.3) 1 (3.1) Incisor tubercle 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Cnine tubercle 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Centrl cusp 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Prmolr tubercle 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Crbelli s cusp 0 (0.0) 0 (0.0) 0 (0.0) 1 (3.1) Anomlies of position Displcement of mxillry cnine 1 (8.3) 2 (10.0) 3 (9.4) 3 (9.4) Mesil ngultion of mxillry cnine 1 (8.3) 0 (0.0) 1 (3.1) 0 (0.0) Distl ngultion of mndibulr second premolr 4 (33.3) 7 (35.0) 11 (34.4) 12 (37.5) Ectopic eruption of molr 0 (0.0) 2 (10.0) 2 (6.3) 1 (3.1) Trnsposed teeth 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Percentges in prentheses. N indictes number of subjects. * P,.05; ** P,.01; *** P,.001. models. Peg-shped lterl incisors, incisor nd cnine tubercles, nd centrl cusps, prmolr tubercles, nd Crbelli s cusps were identified on the study models. Anomlies in Position Anomlies in position were dignosed minly using pnormic rdiogrphs tken t nerly the sme ge for the genesis nd control groups. Dignosis of pltlly or bucclly displced cnines ws mde on the pnormic rdiogrphs nd lterl cephlogrms. Figure 1. Four clsses of mxillry first molr occlusl surfce ptterns. Clss I fetures four well-developed cusps. Clss II hs reduced hypocone. Clss III hs cuspule on the distl border. Clss IV hs no hypocone. P indictes prcone; Me, metcone; Pr, protocone; nd Hy, hypocone. Imges obtined by computed tomogrphic scnning were lso used when it ws difficult to determine cnine displcements. Disloction of mxillry cnine ws regrded s mesil ngultion when the distl ngle formed between the long xis of the cnine nd the occlusl plne (defined by the mesiobuccl crests of the mxillry right nd left first [second] permnent molrs) ws 57.4 degrees or less on the pnormic rdiogrphs. The decision of this criticl ngle ws bsed on the findings by Grnde et l. 12 tht the men mesil inclintion of displced nd retined mxillry cnines ws 57.4 degrees (SD 13.3). Dignosis for mesil ngultion of mxillry cnines ws performed on subjects who were t lest 10 yers old. This criticl ge ws dopted on the bsis of the findings by Ericson nd Kurol 13 tht rdiogrphic exmintions of ptients under the ge of 10 did not provide relible bsis for prognosis of future unfvorble eruption pth of the mxillry cnines. A mndibulr second premolr ws dignosed s presenting distl ngultion when the distl ngle formed between the long xis of the second premolr nd tngent to the inferior border of the mndibulr body ws 73.9 degrees or less on the pnormic

4 MAXILLARY FIRST MOLAR AGENESIS 1005 Tble 3. Numbers nd Percentges of Subjects by Number of Missing Teeth nd with Advnced Tooth Agenesis nd Sttisticl Comprisons Group 1M (N 5 12) Group 2M (N 5 20) Group M Group C Sttisticl Comprisons Number of missing teeth (excluding third molrs nd mxillry first molrs) Kruskl-Wllis Test/P Vlue 0 10 (83.3) 12 (60.0) 22 (68.8) 30 (93.8).010** 1 2 (16.7) 0 (0.0) 2 (6.3) 1 (3.1) Steel-Dwss Test/Significnt Comprison/ P Vlue 2 0 (0.0) 2 (10.0) 2 (6.3) 1 (3.1) Group 2M vs Group C.011* 3 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) Group M vs Group C.044* 4 0 (0.0) 2 (10.0) 2 (6.3) 0 (0.0) 5 0 (0.0) 2 (10.0) 2 (6.3) 0 (0.0) 6 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) Fisher s Exct Test/P Vlue 1M vs 2M 1M vs C 2M vs C M vs C Number of subjects with dvnced tooth genesis (including missing mxillry first molrs) 0 (0.0) 6 (30.0) 6 (18.8) 0 (0.0) **.024* Percentges in prentheses. N indictes number of subjects. * P,.05; ** P,.01. rdiogrphs of subjects who were t lest 10 yers old. This criticl ngle ws bsed on the findings of Shlish et l. 14 tht the men distl inclintion of mndibulr second premolrs ws 85.5 degrees (SD 5.8). This ngle of 73.9 degrees 11.6 degrees smller thn 2 SDs from the men ws used s threshold for the clinicl significnce of distl inclintion. Ectopic eruption of molrs nd trnsposed teeth were identified on the pnormic rdiogrphs. All dentl nomlies were reexmined by the sme investigtor nd nother investigtor independently fter n intervl of 1 month. Either intrexminer or interexminer reproducibility ws 100% in the identifiction of ll dentl nomlies. Sttisticl Anlysis Sttisticl nlyses were performed by the use of SPSS for the Mcintosh, Version 17.0J (SPSS Jpn Inc, Tokyo, Jpn). The chi-squre test or Fisher s exct test ws used to determine the significnt differences in the prevlence rte of dentl nomlies between the groups. The Kruskl-Wllis nd Steel-Dwss tests were used to determine whether nd where significnt differences in the distribution of dentl nomlies occurred between the groups. All sttisticl tests were performed t the P,.05 level of significnce. RESULTS Anomlies in Number Tble 2 shows tht the prevlence rte of genesis of teeth other thn mxillry first nd third molrs ws significntly higher in groups 2M (40.0%) nd M (31.3%) thn in group C (6.3%). Tble 3 shows significnt differences in the distribution of subjects by the number of missing teeth between groups 2M nd C nd between groups M nd C. Tble 3 lso shows tht the prevlence of dvnced tooth genesis, which is defined s five or more missing permnent teeth, including mxillry first molrs nd excluding third molrs, 3 ws clculted t 30% nd 18.8% in groups 2M nd M, respectively, with significnt differences between groups 2M nd C nd between groups M nd C. As shown in Tble 4, the most commonly missing teeth were mxillry nd mndibulr second premolrs (22.6% for ech), followed by mxillry lterl incisors (19.4%) in group 2M, while in groups 1M nd C the only missing tooth ws mndibulr second premolrs. Tble 2 shows tht the prevlence rte of second premolr genesis ws significntly higher in groups 2M nd M thn in group C, while tht of mxillry lterl incisor genesis ws not significntly different between groups. Tble 2 lso shows tht the prevlence rtes of symmetricl tooth genesis, excluding third molrs nd mxillry first molrs, were significntly different between groups 1M nd 2M, between groups 2M nd C, nd between groups M nd C. The most common symmetricl genesis ws exhibited by mxillry lterl incisors nd second premolrs, followed by mndibulr second premolrs (Tble 4). Tble 2 shows tht the prevlence rte of third molr genesis ws significntly lower in group C thn in the other groups. Tble 5 shows significnt differences in the distribution of subjects by the number of missing third molrs between group C nd the other groups. As shown in Tble 5, there were significnt differences in the prevlence rte of missing mxillry

5 1006 ABE, ENDO, SHIMOOKA Tble 4. Numbers nd Percentges of Different Missing Teeth nd Symmetricl Tooth Agenesis Group 1M (N 5 12) Group 2M (N 5 20) Group M Group C Chi-Squre Test or Fisher s Exct Test/P Vlue 1M vs 2M 1M vs C 2M vs C M vs C FDI tooth number Mxill 11 or 21 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 12 or 22 0 (0.0) 6 (19.4) 6 (18.2) 0 (0.0) 13 or 23 0 (0.0) 2 (6.5) 2 (6.1) 0 (0.0) 14 or 24 0 (0.0) 1 (3.2) 1 (3.0) 0 (0.0) 15 or 25 0 (0.0) 7 (22.6) 7 (21.2) 0 (0.0) 17 or 27 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Subtotl 0 (0.0) 16 (51.6) 16 (48.5) 0 (0.0) Mndible 31 or 41 0 (0.0) 2 (6.5) 2 (6.1) 0 (0.0) 32 or 42 0 (0.0) 2 (6.5) 2 (6.1) 0 (0.0) 33 or 43 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 34 or 44 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 35 or 45 2 (100.0) 7 (22.6) 9 (27.3) 3 (100.0) 36 or 46 0 (0.0) 2 (6.5) 2 (6.1) 0 (0.0) 37 or 47 0 (0.0) 2 (6.5) 2 (6.1) 0 (0.0) Subtotl 2 (100.0) 15 (48.4) 17 (51.5) 3 (100.0) Totl 2 (100.0) 31 (100.0) 33 (100.0) 3 (100.0).000*** ***.000*** Symmetricl tooth genesis pttern Mxill 12 nd 22 0 (0.0) 3 (15.0) 3 (9.4) 0 (0.0) 13 nd 23 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) 15 nd 25 0 (0.0) 3 (15.0) 3 (9.4) 0 (0.0) Subtotl 0 (0.0) 7 (5.8) 7 (3.6) 0 (0.0) Mndible 31 nd 41 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) 35 nd 45 0 (0.0) 2 (10.0) 2 (6.3) 1 (3.1) 36 nd 46 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) 37 nd 47 0 (0.0) 1 (5.0) 1 (3.1) 0 (0.0) Subtotl 0 (0.0) 5 (3.6) 5 (2.2) 0 (0.0) Totl 0 (0.0) 12 (4.6) 12 (2.9) 1 (0.2).005** ***.002** Percentges in prentheses. FDI indictes Fédértion Dentire Interntionle. ** P,.01; *** P,.001. third molrs between groups 1M nd 2M, between groups 1M nd C, nd between groups M nd C; significnt differences in the rte of missing mndibulr third molrs between groups 1M nd 2M nd between group C nd the other groups; nd significnt differences in the rte of missing mxillry nd mndibulr third molrs between group C nd the other groups. Tble 5 lso shows tht there were significnt differences in the prevlence rtes of subjects with symmetricl third molr genesis, symmetricl genesis of mndibulr third molrs, nd symmetricl genesis of combined mxillry nd mndibulr third molrs between groups 2M nd C nd between groups M nd C. Tble 6 shows no significnt ssocitions between genesis of third molrs nd other teeth, or between genesis of third molrs nd mndibulr second premolrs in ech group. There were no significnt differences in the prevlence rte of supernumerry teeth or mesiodentes between groups (Tble 2). Anomlies in Shpe nd Position There were no significnt differences in the prevlence rtes of peg-shped lterl incisors, shovelshped incisors, Crbelli s cusps, displcement or mesil ngultion of mxillry cnines, distl ngultion of mndibulr second premolrs, nd ectopic eruption of molrs between groups (Tble 2). Tble 7 shows significnt differences in the distribution of occlusl surfce ptterns between the mxillry first molrs of group C nd the mxillry second molrs of ech group. DISCUSSION In this study, subjects with bilterl genesis of mxillry first molrs presented significntly higher prevlence rtes of genesis of other teeth, excluding third molrs (Tble 2), nd dvnced tooth genesis (Tble 3) thn those without genesis of mxillry first molrs. Aside from the third molr, the most commonly bsent tooth ws the second premolr (Tble 4). Prt of these results my be consistent with the findings of Grib et l. 7 tht there were strong ssocitions between genesis of second premolrs nd other permnent teeth. Bergstrom 1 reported tht, of six children with the bsence of mxillry nd/or mndibulr first molrs, two pirs of siblings hd the bsence of two mxillry first molrs nd four second premolrs

6 MAXILLARY FIRST MOLAR AGENESIS 1007 Tble 5. Distribution of Third Agenesis in Ech Group Group 1M (N 5 12) Group 2M (N 5 20) Group M Group C Sttisticl Comprisons Number of subjects by the number of Kruskl-Wllis Test/P Vlue missing third molrs 0 3 (25.0) 7 (35.0) 10 (31.3) 25 (78.1).001*** 1 3 (25.0) 0 (0.0) 3 (9.4) 2 (6.3) Steel-Dwss Test/Significnt Comprison/P Vlue 2 3 (25.0) 7 (35.0) 10 (31.3) 3 (9.4) Group 1M vs Group C 0.012* 3 2 (16.7) 4 (20.0) 6 (18.8) 1 (3.1) Group 2M vs Group C 0.007** 4 1 (8.3) 2 (10.0) 3 (9.4) 1 (3.1) Group M vs Group C 0.002** Chi-Squre Test or Fisher s Exct Test/P Vlue Number of different missing third molrs b 1M vs 2M 1M vs C 2M vs C M vs C 18 or (50.0) 10 (25.0) 22 (34.4) 9 (14.1).041*.000*** ** 38 or 48 7 (29.2) 24 (60.0) 31 (48.4) 6 (9.4).017*.038*.000***.000*** Totl 19 (39.6) 34 (42.5) 53 (41.4) 15 (11.7) ***.000***.000*** Number of subjects with symmetricl third molr genesis 5 (41.7) 12 (60.0) 17 (53.1) 5 (15.7) ***.002** Symmetricl third molr genesis pttern b 18 nd 28 3 (25.0) 3 (15.0) 6 (18.8) 4 (12.5) nd 48 3 (25.0) 11 (55.0) 14 (43.8) 2 (6.3) ***.001*** Totl 6 (25.0) 14 (35.0) 20 (31.3) 6 (9.4) ***.002** Percentges in prentheses. N indictes number of subjects. b 18, 28, 38, nd 48 indicte Fédértion Dentire Interntionle tooth numbers. * P,.05; ** P,.01; *** P,.001. coincidently, thus supporting our results. From genetic point of view, our results were in greement with the findings of Stockton et l. 10 nd Kpdi et l. 15 tht individuls with bilterl genesis of mxillry first molrs hd congenitlly missing mxillry nd/or mndibulr premolrs in fmily, unique form of dvnced tooth genesis in n utosoml-dominnt mnner cused by PAX9 muttions. Other investigtors stted tht mxillry first molr genesis occurred in individuls with dvnced tooth genesis, 1,3,5 s evidenced by this study. Still other reserchers reported tht dvnced tooth genesis ws cused by MSX1 muttions, with n verge of 11.0 teeth/ person, teeth/person, 16 nd 12.2 teeth/person, 17 nd by PAX9 muttions, with n verge of 13.7 teeth/ person, teeth/person, 15 nd 12.7 teeth/person. 18 Previous studies suggested tht subjects with dvnced hypodonti hd vrious types of symmetri- Tble 6. Number of Subjects with Other Tooth Agenesis (Excluding Mxillry First s) nd Mndibulr Second Premolr Agenesis by Third Agenesis Group 1M (12) Group 2M (20) Group M (32) Group C (32) With Third Agenesis (9) Without Third Agenesis (3) With Third Agenesis (13) Without Third Agenesis (7) With Third Agenesis (22) Without Third Agenesis (10) With Third Agenesis (7) Without Third Agenesis (25) With other tooth genesis Without other tooth genesis Fisher s exct test/ P vlue With second premolr genesis Without second premolr genesis Fisher s exct test/ P vlue Number of subjects in prentheses.

7 1008 ABE, ENDO, SHIMOOKA Tble 7. Distribution of Mxillry Occlusl Surfce Ptterns Group 1M Group 2M Group M (N 5 12) (N 5 40) (N 5 52) Group C (N 5 64) Second s (S) b Second s (S) b Second s (S) b First s (F) Second s (S) Sttisticl Comprisons Clss I 2 (16.7) 6 (15.0) 8 (15.4) 60 (93.8) 16 (25.0) Kruskl-Wllis Test/P Vlue.000*** Clss II 1 (8.3) 10 (25.0) 11 (21.2) 4 (6.3) 20 (31.3) Steel-Dwss Test/Significnt Clss III 4 (33.3) 5 (12.5) 9 (17.3) 0 (0.0) 13 (20.3) Comprison/P Vlue.000*** Clss IV 5 (41.7) 19 (47.5) 24 (46.2) 0 (0.0) 15 (23.4) Group 1M (S) vs Group C (F).000*** Group 2M (S) vs Group C (F) Group M (S) vs Group C (F).000*** Group C (S) vs Group C (F).000*** N indictes number of teeth exmined. b Second molrs locted in the ffected qudrnts. *** P,.001. cl tooth genesis. 6,9,10,15 18 In our study, those subjects with bilterl genesis of mxillry first molrs hd significntly higher prevlence rte of symmetricl tooth genesis, with third molrs excluded, thn those with unilterl genesis nd without genesis of mxillry first molrs (Tbles 2 nd 4). These results were consistent with the findings of previous investigtors 10,15,18 tht, in subjects with dvnced tooth genesis cused by PAX muttions, most ptterns of tooth genesis, including mxillry first molr genesis, were bilterlly symmetricl. In this study, those subjects with unilterl nd bilterl genesis of mxillry first molrs hd significntly higher prevlence rte of third molr genesis thn those without genesis of mxillry first molrs. These results my suggest tht mxillry first molr genesis nd third molr genesis re different phenotypes of the sme genetic defect nd support severl other studies 10,15,18 demonstrting tht s result of PAX9 muttions, lmost ll individuls with bilterl genesis of mxillry first molrs hd bilterl genesis of mxillry nd mndibulr third molrs in fmily with dvnced tooth genesis. From clinicl perspective, our finding tht the subjects with bilterl genesis of mxillry first molrs predominntly hd symmetricl genesis of mndibulr third molrs my be convenient for orthodontists to tret mlocclusions with mxillry first molr genesis, becuse there is no need to extrct molrs if mxillry third molrs re present nd mndibulr third molrs re bsent. On the other hnd, our finding tht the subjects with unilterl genesis of mxillry first molrs predominntly hd mxillry third molr genesis my indicte possibility of the eruption of only one molr in ech of the mxillry qudrnts. Previous studies showed significnt ssocition of third molr genesis with genesis of other teeth, prticulrly second premolrs nd lterl incisors. 7,8 Some investigtors showed tht MSX1 muttions predominntly ffected genesis of both second premolrs nd third molrs. 16,17 Their findings 7,8,16,17 my not support our results tht there were no sttisticlly significnt ssocitions between genesis of third molrs nd genesis of other teeth, including second premolrs nd excluding mxillry first molrs (Tble 6). Different phenotypes between MSX1 9,16,17 nd PAX9 10,15,18 muttions my ccount for the fct tht genesis of both first nd second molrs is observed in fmilies with the PAX9 muttion, thus indicting tht PAX9 muttions ply criticl role in severe molr genesis. Our study found no significnt ssocitions between mxillry first molr genesis nd other dentl nomlies, except for genesis of other teeth. These findings disgreed with those of the study published by Grib et l., 7 who observed sttisticlly significnt ssocitions of second premolr genesis with other dentl nomlies, including microdonti, deciduous molr infrocclusion, nd certin dentl ectopis s well s other permnent tooth genesis. Agenesis of the mxillry first molrs is differentited from delyed eruption of the mxillry first molrs due to immture formtion. 19 Our results showed significnt differences in the distribution of occlusl surfce ptterns between the mxillry first molrs of the control subjects (group C) nd the mxillry second molrs of those with tooth genesis (groups 1M nd 2M). These results reconfirmed our previous findings tht the most nterior mxillry molrs locted in the ffected qudrnts were the erly erupted second molrs cused by the first molr genesis rther thn the lte erupted first molrs cused by immture tooth formtion. CONCLUSIONS N Agenesis of mxillry first molrs is ssocited with higher prevlence of other permnent tooth genesis nd dvnced tooth genesis.

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