Root lengths in the permanent teeth of Klinefelter (47,XXY) men

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<ul><li><p>t t</p><p>Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu and University Hospital of Oulu, Finland</p><p>a r ch i v e s o f o r a l b i o l o g y 5 2 ( 2 0 0 7 ) 8 2 2 8 2 7</p><p>avai lable at www.sc iencedi rec t .com</p><p>ls1. Introduction</p><p>Men with Klinefelter syndrome have two X chromosomes in</p><p>addition to one Y chromosome (47,XXY), or in rare cases three</p><p>or four X chromosomes. This is in fact the most common sex</p><p>chromosome abnormality, with an incidence of 1 in 576</p><p>newborn boys,1 and 1 in 769 has also been suggested.2 The</p><p>incidence of 47,XXY boys increases with maternal age finding</p><p>an explanation in maternal meiosis. Prenatal testosterone</p><p>level of 47,XXY boys does not differ significantly from normal</p><p>men. Later the production of testosterone is insufficient and</p><p>needs to be substituted already from the age of 11 until 50</p><p>years of age. The head circumference, body weight and length</p><p>have been found to be relatively reduced among 47,XXY boys</p><p>at birth.3 They show somewhat greater height growth</p><p>acceleration than normal boys between 5 and 8 years of age</p><p>owing to relatively greater leg growth. The magnitude and</p><p>timing of the pubertal growth spurt is like in normal boys.</p><p>47,XXY men grow taller than normal men, with a mean adult</p><p>height of 186 and 180 cm correspondingly, but remain 810 cm</p><p>shorter than 47,XYY men or males with an extra Y chromo-</p><p>some.2 In a Finnish study the final height in 47,XXY men was</p><p>182 cm.4 The somewhat greater growth acceleration in adult</p><p>height is due to relatively increased leg length and the</p><p>a r t i c l e i n f o</p><p>Article history:</p><p>Accepted 5 February 2007</p><p>Keywords:</p><p>Klinefelter man</p><p>X chromosome</p><p>Y chromosome</p><p>Humans</p><p>Aneuploidy</p><p>Tooth root</p><p>Growth and development</p><p>a b s t r a c t</p><p>Earlier studies on human teeth have provided proof of an expression of the X and Y</p><p>chromosome genes in tooth crown growth. The Y chromosome promotes the growth of</p><p>permanent tooth crown enamel and dentin, whereas the effect of the X chromosome seems</p><p>to be restricted mainly on enamel formation. Also, there are evidences that both of the sex</p><p>chromosomes are expressed in tooth root growth. The permanent tooth crowns in 47,XXY</p><p>males or individuals with an extra X or Y chromosome show increased size compared to</p><p>normal men, which is mainly due to increased enamel thickness, the dentin thickness is</p><p>somewhat reduced. There is some evidence of increased mesio-distal tooth crown size also</p><p>in their primary dentition. The aim of the present study was to determine their complete</p><p>permanent tooth root lengths. The study groups consisted of 49 47,XXY males, 22 relative</p><p>males, 8 relative females, 35 population control males and 46 population control females</p><p>from the Kvantti research project. Root length measurements were made from panoramic</p><p>radiographs on both sides of the jaw using a digital sliding calliper. The results showed</p><p>growth increase in the final tooth root sizes in 47,XXY males which conceivably become</p><p>evident beginning 8 years after birth up to the age of 14 years, at least. The present results</p><p>and earlier ones on 45,X and 45,X/46,XX females, normal females and males indicate that</p><p>the promoting effect of the Y chromosome on tooth root growth is greater than that of the X</p><p>chromosome. These differential effects are conceivably causative factors in the develop-</p><p>ment of the sexual dimorphism in tooth root size.</p><p># 2007 Elsevier Ltd. All rights reserved.</p><p>* Corresponding author. Tel.: +358 8 3153934; fax: +358 8 5375560.E-mail address: raija.lahdesmaki@oulu.fi (R. Lahdesmaki).</p><p>00039969/$ see front matter # 2007 Elsevier Ltd. All rights reserved.doi:10.1016/j.archoralbio.2007.02.002Root lengths in the permanenmen</p><p>Raija Lahdesmaki *, Lassi Alvesalo</p><p>journa l homepage: www. int l .eeeth of Klinefelter (47,XXY)</p><p>evierhea l th .com/ journals /arob</p></li><li><p>dental organ around the growing dental papilla to initiate the</p><p>differentiation of root odontoblasts. The formation of primary</p><p>possible. The other criteria were age, generation and the</p><p>number of the teeth available. The Institutional Review Board</p><p>of the Medical Faculty, University of Turku, Finland, had</p><p>reviewedand approved the protocol, ofwhich the patients and</p><p>their relatives were informed. All examinations were carried</p><p>out with the individuals consent, and the subjects were not at</p><p>risk in any way.</p><p>2.2. Measurements</p><p>Permanent tooth root lengths in maxilla and mandible were</p><p>measured from dental panoramic radiographs and crown</p><p>heights were measured at the same time for further study. All</p><p>the radiographs had been taken by the same person at the</p><p>Institute of Dentistry, University of Turku, following a</p><p>standardized procedure and with the same machine, an</p><p>Orthopantomograph 3, Palomex Corporation, Helsinki, Fin-</p><p>land. Themagnificationwas in the range 1.281.31 throughout</p><p>the image layer of the panoramic radiograph. A magnifying</p><p>lens (2) was used to determine the outlines of the tooth from</p><p>a r c h i v e s o f o r a l b i o l o g y 5 2 ( 2 0 0 7 ) 8 2 2 8 2 7 823physiological dentin continues until the external root form is</p><p>completed.14 Excluding third molars, in terms of population</p><p>developmental standards, permanent tooth roots complete</p><p>their growth on average between the ages of 8 and 14 years.</p><p>In the present study, complete permanent tooth root</p><p>lengths in Klinefelter men (47,XXY males) or individuals with</p><p>extra X or Y chromosome are determined to gain additional</p><p>information about their dental growth and the role of the X</p><p>and Y chromosomes in this process. It has been suggested</p><p>earlier that the genes on the X and Y chromosome that affect</p><p>tooth crown growth are also expressed in the following root</p><p>growth.15</p><p>2. Subjects and methods</p><p>2.1. Subjects</p><p>The patients, their relatives and population controls were all</p><p>participants in Alvesalos Kvantti dental research project on</p><p>individuals with sex chromosome abnormalities. The subjects</p><p>were from different parts of Finland and consisted of 49</p><p>47,XXY males (mean age 30.7 years, S.D. 11.71, minimum</p><p>10.16, maximum 57.61), 22 relative men (16 fathers and 6</p><p>brothers) (mean age 41.0 years, S.D. 15.53, minimum 13.52,</p><p>maximum 67.50), 8 relative women (mothers) (mean age 39.7</p><p>years, S.D. 5.64, minimum 31.17, maximum 50.55), 35 popula-</p><p>tion control men (mean age 25.5 years, S.D. 12.41, minimum</p><p>11.60, maximum 45.64) and 46 population control women</p><p>(mean age 27.6 years, S.D. 10.66, minimum 9.74, maximum</p><p>55.63), who were relatives of patients other than 47,XXY men</p><p>in the Kvantti research project. The diagnoses of the patients</p><p>were based on clinical and karyotypic evidence. All their</p><p>cytogenetic diagnosis had been carried out for medical</p><p>reasons. For comparisons the relatives were chosen on afeminine trunk proportions in 47,XXY males are caused by a</p><p>decrease in shoulder width, possibly affected by the double</p><p>dose of X chromosomes. Their adult head circumference is</p><p>under normal men, but above normal women,4 also, their</p><p>facial dimensions are smaller than those in normal men.4,5</p><p>Interestingly enough, 47,XXX females or femaleswith an extra</p><p>X chromosome also show reduced head and skull size,6 and</p><p>they are tall because of relatively increased leg length.</p><p>The total permanent tooth crown size increase in 47,XXY</p><p>males is caused by thicker enamel layer relative to normal</p><p>men or women, the dentin thickness is less than in men, but</p><p>above that of women.7 Larger tooth crown size in normal men</p><p>relative to women is due to the thicker dentin layer inmen,810</p><p>and men also show longer roots than women.11,12 A case</p><p>report of increased mesio-distal tooth crown size in the</p><p>primary dentition13 of a 47,XXY male is parallel with the</p><p>results of the permanent dentition.7 After the crown growth is</p><p>completed the epithelial cells in the tooth root sheath</p><p>determine the size, shape and number of the roots.14 Root</p><p>dentin is formed later than crown dentin and requires a</p><p>proliferation of epithelial cells from the cervical loop of thepaired basis, one relative of the same phenotypic sex for each</p><p>patient and comparisons were also extended to opposite sex ifthe radiograph on a light table, after which the outlines were</p><p>marked with a special pencil for plaster (Schwan All Stabilo</p><p>8008, Schwanhauber GmbH &amp; CO, KG Heroldsberg, Germany)</p><p>and the measurements made in the same manner with a</p><p>sliding digital calliper (Mitutoyo, digimatic 500-123U, CD-15B,</p><p>Andover, England) to an accuracy of 0.01 mm. The outlines of</p><p>the roots were hard to determine in places and the drawings</p><p>had to be made straight on the radiograph. All the drawings</p><p>and measurements were made by one of the authors (RL)</p><p>(Fig. 1a). The measurements of root lengths were made</p><p>perpendicular to two parallel lines, one touching the outer-</p><p>most part of the root and the other joining the mesial and</p><p>distal cervical margins of the enamel (Fig. 1b). Root length</p><p>refers to the longest root on the radiograph in the case of</p><p>premolars and the longest mesial root in the case of molars.</p><p>The aim was to measure all the teeth with complete root</p><p>formation on both sides of the jaws except for the third</p><p>molars. Teeth that were partly outside the plane-in-focus in</p><p>Fig. 1 Root lengths were measured by reference to linesmarked on the tomographic radiographs (a) as described</p><p>in the text and shown in the picture (b).</p></li><li><p>show numerically larger values in root length in 22 measure-</p><p>on dentin, can explain the expression of somatic sexual</p><p>a r c h i v e s o f o r a l b i o l o g y 5 2 ( 2 0 0 7 ) 8 2 2 8 2 7824the panoramic radiograph or showed obvious distortion</p><p>because of being on the inner or outer surface of the image</p><p>layer16 were excluded. Teeth with root resorption or incom-</p><p>plete root formation were also excluded, but teeth with large</p><p>restorations or large caries lesions with pronounced loss of</p><p>crown structure were measured whenever possible. Dilacer-</p><p>ated or crooked roots were measured in terms of perpendi-</p><p>cular length as explained above. Some impacted canine teeth</p><p>with a closed apex were measured. Acellular cementum is</p><p>formed on the root surface until the tooth reaches the</p><p>occlusion, at which time the proliferation of the epithelial</p><p>root sheath is reduced and it may become entrapped within</p><p>the forming matrix of cellular cementum.17 Cellular cemen-</p><p>tum formation continues after the root form is complete. The</p><p>line between apical cementum and dentin was evaluated</p><p>while marking the outlines of the roots and the apical</p><p>cementum layer was excluded from the present root length</p><p>determinations.</p><p>Permanent tooth root lengths may be affected by several</p><p>external factors, which could bias the results. Orthodontic</p><p>treatment, especially with fixed appliances, may cause root</p><p>resorption, as also can traumatic occlusion, bruxism, nail-</p><p>biting, trauma, apical infection or root treatment, for instance.</p><p>According to anamnestic information, the patients or their</p><p>relatives had not had any orthodontic treatment, at least with</p><p>fixed appliances, before the examination procedures. Simi-</p><p>larly, anamnestic information on the population controls</p><p>suggested that they had not undergone orthodontic therapy.</p><p>This is supported by the fact that at the time in question there</p><p>were only very few dental offices in Finland where fixed</p><p>appliance orthodontics, or orthodontics in general, were</p><p>carried out. Regarding the possible effects of other external</p><p>factors, an assumption was made of an even distribution</p><p>between the groups.</p><p>The reliability of the measurements was examined by</p><p>performing double determinations on a total of 45 dental</p><p>radiographs from the Kvantti research material representing</p><p>adult 45,X females and their relativemen and women, with 15</p><p>persons in each group. The measurements were made by the</p><p>same person (RL) at an interval of 2 weeks, the line joining the</p><p>mesial and distal cervical margins of the enamel marked on</p><p>each tooth being rubbed out after the first measurement and</p><p>determined again and re-drawn for the second. The reprodu-</p><p>cibility of the double determinations of root length was</p><p>expressed with the method error statistic (S) (x1 = original</p><p>measurement value, x2 = repeated measurement value,</p><p>n = number of patients) S P x1 x22=2n</p><p>q.18</p><p>The absolute error values for the root length measure-</p><p>ments ranged from 0.35 to 0.75 mm, the corresponding</p><p>percentages being 1.95 and 5.11. The largest differences in</p><p>the double determinations of root lengths were in the upper</p><p>second premolars and molars and mandibular incisors and</p><p>canines. The values were considered acceptable for further</p><p>measurements.</p><p>2.3. Statistical analysisThe Statistical Package for the Social Sciences 10.0 (SPSS, CA,</p><p>USA)was used for the statistical analysis. Mean values for rootdimorphism in the crown size, shape, maturation and in the</p><p>number of the teeth, e.g. supernumerary permanent teeth are</p><p>approximately twice as common in normal men than in</p><p>women, and ordinary teeth are more frequently missing in</p><p>women than in men.20,22,23 Also, assuming genetic pleiotropy,</p><p>sexual dimorphism in root size,12 in the expression of torusments out of 28 (Table 2), and the roots of relative men are</p><p>generally longer than those of relative women. It is notable</p><p>that the differences of root lengths between 47,XXYmales and</p><p>control women are larger with one exception than those</p><p>between 47,XXY males and control men. Visual inspection of</p><p>the root morphology on the radiographs of 47,XXY males did</p><p>not reveal any major deviations from normality. However,</p><p>minor deviation in the form of taurodontic teeth was present</p><p>in mild expression in 30% of the cases. Taurodontism is an</p><p>extension of the pulp chamber in which the furcation of the</p><p>roots takes place more apically in multirooted teeth. The fact</p><p>that themean root lengths of antimeric teeth differed to some</p><p>extentmay be due to the sample sizes, the varying numbers of</p><p>measurements available and general technical reasons.</p><p>Certainly, the measurements of natural tooth roots also show</p><p>differences between the mean lengths for antimeric teeth.11</p><p>4. Discussion</p><p>Studies on families19,20 and individuals with sex chromosome</p><p>abnormalities,8,2123 and molecular research,2426 have pro-</p><p>vided proof of an expression of the X andY chromosomegenes</p><p>in tooth crown growth. The Y chromosome promotes growth</p><p>of permanent tooth crown enamel and dentin, whereas the</p><p>effect of the X chromosome in tooth crown growth seems to be</p><p>restricted mainly on enamel formation.22,23 Enamel growth is</p><p>decisively influenced by cell secretory function and that of</p><p>dentin by cell proliferations.27 The promoting effect of the Y</p><p>chromosome genes on tooth crown development, particularlylength were calculated and compared between the 47,XXY</p><p>males, relative men (47,XXY male versus father or brother),</p><p>population control men and women using the t-test for</p><p>equality of means to indicate the significance of differences</p><p>between the groups. Results were considered statistically</p><p>significant when p was 0.05 or less.</p><p>3. Results</p><p>The results show that mean permanent tooth root lengths in</p><p>47,XXY males are generally longer than those in normal</p><p>control men (Table 1). In the mandibl...</p></li></ul>

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