Panoramic Radiographic Evaluation of Dental Anomalies, Dental Mineralization Stage, and Mandibular Angle
www.scielo.br/jaos http://dx.doi.org/10.1590/1678-775720160170 Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle
Aida SABBAGH-HADDAD1, Denise Sabbagh HADDAD2, Edgard MICHEL-CROSATO3, Emiko Saito ARITA2
1- Associação Paulista de Cirurgiões-Dentistas, Departamento de Odontologia para Pacientes com Necessidades Especiais, São Paulo, SP, Brasil. 2- Universidade de São Paulo, Faculdade de Odontologia, Departamento de Estomatologia, Disciplina de Radiologia, São Paulo, SP, Brasil. 3- Universidade de São Paulo, Faculdade de Odontologia, Departamento de Odontologia Social, São Paulo, SP, Brasil.
Corresponding address: Denise Sabbagh Haddad - Av. Professor Lineu Prestes, 2227 - Cidade Universitária - São Paulo - SP - 05508-000 - Phone: 55(11)3091-7831 - e-mail: [email protected]
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ABSTRACT
ragile X syndrome (FXS) is a disorder linked to the chromosome X long arm (Xq27.3), FZKLFKLVLGHQWL¿HGE\DFRQVWULFWLRQQDPHGIUDJLOHVLWH,WGHWHUPLQHVYDULRXVFKDQJHV VXFKDVEHKDYLRUDORUHPRWLRQDOSUREOHPVOHDUQLQJGLI¿FXOWLHVDQGLQWHOOHFWXDOGLVDELOLWLHV Craniofacial abnormalities such as elongated and narrow face, prominent forehead, broad nose, large and prominent ear pavilions, strabismus, and myopia are frequent characteristics. Regarding the oral aspects, deep and high-arched palate, mandibular prognathism, and malocclusion are also observed. Objective: The purpose of this study was to evaluate the dental radiographic characteristics as described in 40 records of patients with panoramic radiography. Material and Methods: The patients were in the range of 6-17 years old, and were divided into two groups (20 subjects who were compatible with the normality standard and 20 individuals diagnosed with the FXS), which were matched for gender and age. Analysis of the panoramic radiographic examination involved the evaluation of dental mineralization stage, mandibular angle size, and presence of dental anomalies in both deciduous and permanent dentitions. Results: The results of radiographic evaluation demonstrated that the chronology of tooth eruption of all third and second lower molars is anticipated in individuals with FXS (p<0.05). In this group, supernumerary deciduous teeth (2.83%), giroversion of permanent teeth (2.31%), and partial anodontia (1.82%) were the most frequent dental anomalies. In addition, an increase was observed in the mandibular angle size in the FXS group (p<0.05). Conclusion: We conclude that knowledge of dental radiographic changes is of great importance for dental surgeons to plan the treatment of these individuals.
Keywords: Fragile X syndrome. Intellectual disability. Tooth abnormalities. Panoramic radiography. Dentistry.
INTRODUCTION region of the gene, which is located at the distal portion (Xq27.3) of the X-chromosome long arm. Fragile X (Martin-Bell) Syndrome (FXS) is an The fragile region is a gap, which is not stained inherited genetic disease, which is little known by cytological dyes and usually involves both by most professionals in the health area. For this chromatids at a point where the chromosome is reason, its actual incidence in the population is still susceptible to break. This characteristic can be unknown although its prevalence is known to be FRQ¿UPHG E\ NDU\RW\SH H[DPLQDWLRQ VLQFH WKH high. Recent studies have shown a pre-mutation VSHFL¿F LQYHVWLJDWLRQ WHFKQLTXH IRU IUDJLOH VLWHV prevalence in men (1:430) and women (1:209) in is used. In men, the diagnosis is made indirectly the USA16. through the polymerase chain reaction (PCR) The FXS designation is related to a fragile method. In women, however, this method is not
J Appl Oral Sci. 518 2016;24(5):518-23 Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle
VXI¿FLHQWWRLQGLFDWHPXWDWLRQLQWKHJHQHDQGWKH fragile X syndrome. use of Southern Blot and Hybridization methods LVQHFHVVDU\IRU¿QDOGLDJQRVLVRIWKHV\QGURPH1. MATERIAL AND METHODS 0ROHFXODU VWXGLHV LGHQWL¿HG WKLV PXWDWLRQ LQ the Fragile X Mental Retardation type-1 (FMR1) This study was approved by the Institutional gene, which is located on the X chromosome, Review Board (CAAE 46419215.7.0000.0075) of and explains the fragile site in the subterminal the School of Dentistry, University of São Paulo portion of its long arm. Variable effects can (FOUSP). be observed in the phenotypic constitution of Forty clinical forms were selected. They included individuals with the syndrome due to a gene panoramic radiographic exams of individuals aged permutation and expansions observed in the Fragile between 6-17 years. These forms are part of the X Mental Retardation Protein (FMRP) (greater database of the author’s private clinic. or smaller amount of CGG nucleotides)6,9. The The sample was divided into two groups: 20 alteration in the FMRP is repeated in body cells, SDWLHQWVGLDJQRVHGZLWK);6FRQ¿UPHGE\PROHFXODU affecting various organic structures and functions, analysis (method of double digestion of genomic mainly those linked to the cognitive ability. Thus, DNA by the EcoRI and Eagle enzymes, followed by intellectual disability is the most important clinical Southern blot and hybridization with the StB12.3 manifestation, which is caused because the FMRP is probe), named FXS group and 20 individuals absent in the brain of these patients18,19. The degree compatible with the normal pattern, which were of intellectual disability is extremely variable, even called control group. Both groups were matched among individuals from the same family. However, for gender and age, including individuals with VHYHUHGH¿FLHQF\VHHPVWREHWKHPRVWIUHTXHQW deciduous, mixed, and permanent dentition. All of manifestation, which occurs in 42.0% of men them had anamnesis, oral clinical examination, and affected by this mutation7. panoramic radiographic examination. Given the variable clinical aspects, the consensus By panoramic radiographic evaluation (Figure in the literature is that the chromosomal or molecular 1), two radiologists analyzed the mandibular study of individuals with intellectual disability angle size, chronology of eruption according to of unknown origin is mandatory to identify the Nolla’s criteria10, and the dental anomalies related individuals affected by the FXS mutation1,6,7,9,16,18,19. to changes in shape, volume, position such as In the FXS, the typical clinical presentation shows macrodontia, microdontia, fusion, gemination, a classic triad, formed by macroorchidism (in men), concrescence, taurodontism, root fusion and large and prominent ear pavilions, and elongated laceration, dens in dente, transposition, giroversion, and narrow face7. In these individuals, the face is imperfect amelogenesis, partial anodontia, longer because their mandibles suffer a downward dental, root supernumerary, dental number of all rotation4. Their cephalic perimeter is increased and deciduous and permanent teeth, whether erupted the bizygomatic diameter and internal intercanthal or not. The kappa and intraclass correlation (ICC) distance are diminished. In addition, their height, coeI¿cients were used to test the intra- and inter- wingspan, and length of hands, feet, and digits are rater reliability. DOVRVLJQL¿FDQWO\LQFUHDVHG2. Nolla10 calculated the dental mineralization The behavioral characteristics present in the stage dividing the development of each tooth in );6 LQFOXGH SRRU H\H FRQWDFW ÀDSSLQJ KDQGV 10 stages, since the presence of dental crypt until defensive physical contact, and impulsivity, as well the complete formation of the apex10. The author as hyperactivity aggressiveness, anxiety, and self- separated tables for men and women, where the mutilation5,13. DYHUDJHFDOFL¿FDWLRQVWDJHVZHUHUHFRUGHGIRUHDFK The oral and facial clinical examination is a tooth in the age range of 6-17 years. priority in Dentistry, but few studies were found in The panoramic radiographs were analyzed the databases addressing the oral manifestations using a negatoscope, and the dental mineralization of the FXS. However, some authors cite deep and stages were interpreted using the Nolla’s 10-stage high-arched palate and prominent jaw as the main diagrams of dental development10. characteristics of FXS5,11. Furthermore, the presence Measurements of the mandibular angle were of macroglossia, partial anodontia, stains and obtained by the intersection of linear measurements enamel hypoplasia, shape anomalies, macrodontia, tangential to the mandible ramus and inferior and unilateral and bilateral crossbite have also been border. reported13. All data were compiled into a spreadsheet using The purpose of this study was to evaluate the WKH2I¿FH0LFURVRIW([FHO 0LFURVRIW&RUSRUDWLRQ dental structure alterations, mandibular angle Redmond, WA, USA) program. The SPSS 19® (IBM measurements, and dental mineralization stage Corporation; Armonk, NY, USA) program was through panoramic radiography, in individuals with used to obtain the descriptive statistics, Pearson’s
J Appl Oral Sci. 519 2016;24(5):518-23 SABBAGH-HADDAD A, HADDAD DS, MICHEL-CROSATO E, ARITA ES correlation coefficients, and Student’s t test. intra- and interobserver agreement in all dental Differences, associations, and correlations were anomalies. ICC was used to test intra- and inter- FRQVLGHUHG VLJQL¿FDQW ZKHQ WKH WHVW GHVFULSWLYH rater reliability in the Nolla stage and mandibular level (p) was lower than 0.05. DQJOH PHDVXUHPHQWV %RWK FRHI¿FLHQWV LQGLFDWH The relationship between measurements was strong correlation (>0.8) between the parameters HYDOXDWHGE\WKH3HDUVRQ¶VFRUUHODWLRQFRHI¿FLHQW p), analyzed. ZKLFKZDVHYDOXDWHGZKHQVLJQL¿FDQWFRUUHODWLRQV In most panoramic radiographic exams of our were found. Absolute p values suggest weak sample, the age group included both deciduous (|p_ PRGHUDWH _p|<0.7), and strong and permanent dentition. Thus, we evaluated (|p_ FRUUHODWLRQV separately the frequency of dental anomalies in the deciduous and permanent dentitions in both RESULTS control and FXS groups (Table 1). The control group did not show dental anomalies in the The panoramic radiographs were analyzed by deciduous dentition (n=138). However, some WZRREVHUYHUV.DSSDFRHI¿FLHQWZDVXVHGWRWHVW alterations were present in the permanent dentition
Figure 1- Panoramic radiography with the mandibular angle lines
Table 1- Frequency of dental anomalies (per tooth) in the FXS and control groups
Dental Anomalies Deciduous teeth Permanent teeth Control group FXS group Control group FXS group (n=605) (n=138) (n=106) (n=608) %%%% Macrodontia 0 0 0 0 Microdontia 0 0 0.16 0 Fusion 0 0 0 0 Gemination 0 0 0 0 Concrescence 0 0 0 0 Taurodontism 0 0 0 0 Fused roots 0 0 0 0.99 Laceration roots 0 0 0.82 1.16 Dens in dente 0 0 0 0 Transposition 0 0 0 0 Giroversion 0 0.94 0.99 2.31 Amelogenesis imperfecta 0 0 0 0 Partial anodontia 0 0 0.49 1.82 Supernumerary tooth 0 2.83 0 0 Supernumerary root 0 0 0.99 0.33
J Appl Oral Sci. 520 2016;24(5):518-23 Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle
Table 2- Measurements of mandibular angles in patients of the control and fragile X syndrome (FXS) groups
Groups n Right side Left side M ± SD Min-Max M ± SD Min-Max Control 20 122.7 ± 5.7 112-132 123.0 ± 6.3 108-136 FXS 20 131.8 ± 5.9 120-144 130.4 ± 7.6 120-142 p<0.001; M: mean values; SD: standard deviations
Table 3- Pearson’s test for correlation between age and left and right mandibular angles
Age Right angle Left angle Age 1 Right angle -0.123* 1 Left angle -0.114 0.792 1
* p =0.449
(n=608): microdontia (0.16%), root laceration The radiographic examination is one of the (0.82%), giroversion (0.99%), partial anodontia most affordable complementary examinations (0.49%), and supernumerary roots (0.99%). In used in Dentistry for diagnosis, planning, and the deciduous dentition (n=106), the FXS group implementation of treatment, being useful in all presented giroversion (0.94%) and supernumerary dental specialties. Panoramic radiographs are tooth (2.83%). In the permanent dentition (n=605), among those examinations, being a part of dental we observed fused roots (0.99%), root laceration surgeon routine due to the operational simplicity (1.16%), giroversion (2.31%), partial anodontia of the equipment, low-dose radiation, low cost, yet (1.82%), and supernumerary roots (0.33%). allowing examination of a large area of the maxilla We evaluated all panoramic radiographic exams and mandible. Furthermore, it is widely used in for eruption chronology by the Nolla’s approach10, epidemiological studies in the evaluation of dental separated the two groups, and observed that injuries and anomalies, whose knowledge is of great individuals with the FXS showed accelerated value for studies in certain populations. eruption in the upper (18, p=0.063; 28, p=0.024) Analysis of digital panoramic radiographs (1937) and lower (38, p=0.033; 48, p=0.026) third of individuals aged 10-34 years showed that dental molars, and lower second molars (37, p=0.004; absence by tooth extraction, partial anodontia, 47, p=0.001). extrusion, migration, transposition, giroversion, The bilateral mandibular angle measurements and carious and periapical injuries were the most were evaluated and the FXS group showed an frequent injuries and alterations, with higher LQFUHDVH VWDWLVWLFDOO\VLJQL¿FDQWDVFRPSDUHG prevalence in women. The ones less common in with the control group (p<0.001; Table 2). this group were: changes in the condylar head, The Pearson’s test for correlation between age hypercementosis, mandibular fracture, odontoma, and mandibular angle indicated a weak correlation dentigerous cyst, keratocystic odontogenic tumor, (p=0.44) (Table 3). cement-bone periapical dysplasia, foreign body, and cleft palate17. DISCUSSION Isolated cases of dental radiographic evaluation RI);6KDYHDOVREHHQSXEOLVKHG2QHVWXG\LGHQWL¿HG The fragile X syndrome is a genetic disease with the presence of mesiodens and taurodontism in the a great variability in clinical presentation. Until the XSSHU¿UVWDQGVHFRQGSHUPDQHQWPRODUV8. Other 1990s, this syndrome was diagnosed by clinical author reported the presence of non-erupted signs and chromosomal study (karyotype). However, supernumerary tooth in the apical region of the UHFHQWVWXGLHVKDYHFRQ¿UPHGWKDWWKH3&5PHWKRG upper right central incisor, without change in the LVQRWVXI¿FLHQWWRLQGLFDWHPXWDWLRQLQWKH)05 eruption chronology4. gene in women affected by the disease. Since this ,QGLYLGXDOVZLWK);6VKRZVSHFL¿FFKDUDFWHULVWLFV discovery, the molecular exam has been included such as low caries prevalence, problems of cross IRU¿QDOGLDJQRVLVRIWKHV\QGURPH1,6,7,9,16,18,19. and open bite, severe occlusal wear and dental Due to the FMR1 gene permutation and FMRP changes including impacted canine, congenital expansions, variable effects have been observed in absence of premolar, premolar supernumerary, the phenotypic constitution of syndromic patients6,9. and a large hypoplastic defect in a tooth alone, as
J Appl Oral Sci. 521 2016;24(5):518-23 SABBAGH-HADDAD A, HADDAD DS, MICHEL-CROSATO E, ARITA ES compared with normal individuals15. diseases, infectious processes, climate, and In our study, supernumerary deciduous teeth constitutional types. Although dental eruption is (2.83%), giroversion (2.31%), partial anodontia LQÀXHQFHGE\JHQHWLFDQGHQYLURQPHQWDOIDFWRUV (1.82%), lacerated (1.16%) and fused roots in most cases it keeps a certain pattern, which (0.99%), and supernumerary root (0.33%) in the can be applied in legal medicine to estimate permanent teeth were the most frequent dental the chronological age of individuals without an anomalies in the FXS group. LGHQWL¿FDWLRQ GRFXPHQW DV ZHOO DV LQ WKH GHQWDO As observed in our study, partial anodontia treatment planning. is a disorder in which there is a failure in the Kotilainen and Pirinen3 (1999) evaluated the dental development of deciduous or, more often, dental development of 28 boys (aged 4.9-17.6 permanent dentition. Partial anodontia is associated years) with FXS and three girls (aged 5.8, 10.4, with certain disorders such as ectodermal dysplasia, and 12.7 years) who were FXS carriers. They used Down’s syndrome, and cleft lip and palate14. This the Demirjian and Goldstein (1976) criteria for association also occurs in supernumerary teeth tooth development and those of Hagg and Taranger related to the Gardner syndrome and cleidocranial (1985) for tooth eruption, and compared the stature dysplasia, which is caused by an autosomal data and bone maturity growth of the individuals. dominant gene. Although the exact prevalence They concluded that the clinical dental eruption of of isolated hypodontia or supernumerary teeth is deciduous and permanent teeth in men with FXS unknown, in many cases there is a familial tendency was precocious as compared with that observed in for this defect. It results from mutations in the FRQWUROVRIWKHVDPHDJH7KHGHQWDOFDOFL¿FDWLRQ polygenic system, which is most often transmitted stage was anticipated in men and heterozygous in an autosomal dominant manner, with incomplete carrier women, and the height and bone maturity penetrance and variable expression. Although FXS growth did not show an anticipated development. is an inherited genetic disease, these radiographic Our results were different from those of Kotilainen ¿QGLQJVFDQQRWEHDWWULEXWHGWRVSHFL¿FIHDWXUHVRI and Pirinen3 UHJDUGLQJGHQWDOFDOFL¿FDWLRQ the syndrome. Further studies should be done to which was anticipated, and dental eruption, which FRQ¿UPWKHVH¿QGLQJV was precocious in all teeth, because the evaluation In all studies involving the fragile X syndrome, criteria were different. the relationship between age and mandibular angle was not investigated. Measurement of the CONCLUSION mandibular angle, which is the angle between mandibular body and ramus, has been used as Individuals with the fragile X syndrome a tool to determine the age of individuals. In the showed a higher frequency of dental anomalies range of 3-13 years, age is inversely proportional (supernumerary deciduous teeth (2.83%), (in degrees) to the angle12. According to our study, giroversion (2.31%), partial anodontia (1.82%), individuals with the fragile X syndrome exhibit lacerated roots (1.16%), fused roots (0.99%), and an 8-degree increase in the mandibular angle supernumerary root (0.33%) in the permanent when compared with the normal range (p<0.05). teeth) when compared with the control group. However, Pearson’s correlation test indicated a Additionally, an increase was observed in the weak correlation between age and the measures of mandibular angle and acceleration in the eruption mandibular angle in both groups. This age group chronology of upper and lower third molars and was chosen based on the mandibular bone growth lower second molars. phase. However, the age range, compared with the Dental surgeons should consider the changes in sample size, is far too wide (6-17 years) to allow a WKHVH¿QGLQJVWRREWDLQDEHWWHUGHQWDOSODQQLQJDQG GH¿QLWLYHFRQFOXVLRQRQWKHLQFUHDVHLQPDQGLEXODU treatment in individuals with the fragile X syndrome. angle with age. We suggest that panoramic radiography is Some classic facial characteristics in individuals included in the usual skeletal radiographic analysis with FXS, such as long face4,7, downward mandibular of individuals with FXS to better analyze their rotation7 and skeletal open bite14, do not meet our mineralization stages, dental anomalies, and results regarding the increase in the mandibular mandibular angle measurements and thus better angle. Our results suggest that the long face classify their phenotypes. observed in the patients with FXS2,4,7,15 could explain the increase in mandibular angle. Further evaluation RIFHSKDORPHWULFVWXGLHVLVQHFHVVDU\WRFRQ¿UPWKH above mentioned hypothesis. The dental development and its eruption FKURQRORJ\ PD\ EH LQÀXHQFHG E\ D QXPEHU RI factors such as ethnic group, gender, diet, systemic
J Appl Oral Sci. 522 2016;24(5):518-23 Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle
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