effect of down syndrome on the dimensions of dental crowns and tissues

9
Effect of Down Syndrome on the Dimensions of Dental Crowns and Tissues EMMA BELL, 1 GRANT TOWNSEND, 1 * DAVID WILSON, 1 JULES KIESER, 2 AND TOBY HUGHES 1 1 The University of Adelaide, Dental School, South Australia 2 The University of Otago, School of Dentistry, Dunedin, New Zealand ABSTRACT Abnormal growth in Down syndrome (DS) is reflected by variable reduction in size and simplification in form of many physical traits. This study aimed to compare the thickness of enamel and dentine in deciduous and permanent mandibular incisor teeth between DS and non-DS individuals and to clarify how these tissues contribute to altered tooth size in DS. Sample groups comprised 61 mandibular incisors (29 permanent and 32 deciduous) from DS individuals and 55 mandibular incisors (29 permanent and 26 deciduous) from non-DS individuals. Maximum mesiodistal and labiolingual crown dimensions were measured initially, then the crowns were sectioned midsagittally and photographed using a stereomicroscope. Linear measurements of enamel and dentine thickness were obtained on the labial and lingual surfaces of the crowns, together with enamel and dentine–pulp areas and lengths of the dentino-enamel junction. Reduced permanent crown size in DS was associated with a reduction in both enamel and dentine thickness. After adjustments were made for tooth size, DS permanent incisors had significantly thinner enamel than non-DS permanent teeth. The DS permanent teeth also exhibited significant differences in shape and greater variability in dimensions than the non-DS permanent teeth. Crown dimensions of de- ciduous incisors were similar in size or larger in DS compared with non-DS deciduous teeth. Enamel and dentine thicknesses of the deciduous teeth were similar in DS and non-DS individuals. The findings indicate that growth retardation in DS reduces both enamel and dentine deposition in the permanent incisors but not in the earlier-forming deciduous predecessors. The results are also con- sistent with the concept of amplified developmental instability for dental traits in DS. Am. J. Hum. Biol. 13:690–698, 2001. © 2001 Wiley-Liss, Inc. Dental features associated with Down syndrome include microdontia of the perma- nent dentition (Cohen and Winer, 1965; Barden, 1980; Townsend, 1983), altered crown morphology including different cusp patterns on molars and flattened or concave labial surfaces on lower incisors (Prahl- Andersen and Oerlemans, 1976; Townsend and Brown, 1983; Brown and Townsend, 1984) simplified root canal morphology and reduced root and crown length (Kelsen et al., 1999), enamel hypoplasia, hypocalcifica- tion, and hypodontia (McMillan and Kash- garian, 1961; Kisling, 1966; Cohen and Co- hen, 1971). A generalised retardation in growth, consistent with reduced mitotic ac- tivity and proliferation of trisomic cells, has been proposed to be associated with the characteristic DS phenotype (Mittwoch, 1972; Antonucci et al., 1997). This has been supported by in vitro studies showing that the mitotic cycle of trisomic cells is longer than that of normal cells, principally be- cause the G2 period of the cycle is increased by approximately 3 hr compared with nor- mal (Paton et al., 1974). Other studies also lend support to the notion of a growth retar- dation in trisomic cells, including investiga- tions indicating delayed cellular activity during odontogenesis in trisomy 16 mice (Di Stefano and Provenza, 1993), and those showing a reduced number of cells in many body organs of fetuses with Down syndrome (Naeye, 1967). The critical stage of tooth development begins around 4 weeks in utero with the for- mation of deciduous enamel organs and pro- liferation of the inner enamel epithelium and concludes with mineralisation of the dental crowns (Nery et al., 1975). As calci- fication spreads in different directions to de- fine the future dentino-enamel junction, crown morphology is essentially determined (Dalhberg, 1971). Variations in growth rates of the different dimensions of forming *Correspondence to: Professor Grant Townsend, Dental School, The University of Adelaide, South Australia 5005. E-mail: [email protected] Received 14 December 2000; Revision received 28 March 2001; Accepted 16 April 2001 AMERICAN JOURNAL OF HUMAN BIOLOGY 13:690–698 (2001) © 2001 Wiley-Liss, Inc. PROD #M20089R

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Page 1: Effect of Down syndrome on the dimensions of dental crowns and tissues

Effect of Down Syndrome on the Dimensions of DentalCrowns and Tissues

EMMA BELL,1 GRANT TOWNSEND,1* DAVID WILSON,1 JULES KIESER,2 ANDTOBY HUGHES1

1The University of Adelaide, Dental School, South Australia2The University of Otago, School of Dentistry, Dunedin, New Zealand

ABSTRACT Abnormal growth in Down syndrome (DS) is reflected by variable reduction in sizeand simplification in form of many physical traits. This study aimed to compare the thickness ofenamel and dentine in deciduous and permanent mandibular incisor teeth between DS and non-DSindividuals and to clarify how these tissues contribute to altered tooth size in DS. Sample groupscomprised 61 mandibular incisors (29 permanent and 32 deciduous) from DS individuals and55 mandibular incisors (29 permanent and 26 deciduous) from non-DS individuals. Maximummesiodistal and labiolingual crown dimensions were measured initially, then the crowns weresectioned midsagittally and photographed using a stereomicroscope. Linear measurements ofenamel and dentine thickness were obtained on the labial and lingual surfaces of the crowns, togetherwith enamel and dentine–pulp areas and lengths of the dentino-enamel junction. Reduced permanentcrown size in DS was associated with a reduction in both enamel and dentine thickness. Afteradjustments were made for tooth size, DS permanent incisors had significantly thinner enamelthan non-DS permanent teeth. The DS permanent teeth also exhibited significant differences in shapeand greater variability in dimensions than the non-DS permanent teeth. Crown dimensions of de-ciduous incisors were similar in size or larger in DS compared with non-DS deciduous teeth. Enameland dentine thicknesses of the deciduous teeth were similar in DS and non-DS individuals. Thefindings indicate that growth retardation in DS reduces both enamel and dentine deposition in thepermanent incisors but not in the earlier-forming deciduous predecessors. The results are also con-sistent with the concept of amplified developmental instability for dental traits in DS. Am. J. Hum.Biol. 13:690–698, 2001. © 2001 Wiley-Liss, Inc.

Dental features associated with Downsyndrome include microdontia of the perma-nent dentition (Cohen and Winer, 1965;Barden, 1980; Townsend, 1983), alteredcrown morphology including different cusppatterns on molars and flattened or concavelabial surfaces on lower incisors (Prahl-Andersen and Oerlemans, 1976; Townsendand Brown, 1983; Brown and Townsend,1984) simplified root canal morphology andreduced root and crown length (Kelsen etal., 1999), enamel hypoplasia, hypocalcifica-tion, and hypodontia (McMillan and Kash-garian, 1961; Kisling, 1966; Cohen and Co-hen, 1971). A generalised retardation ingrowth, consistent with reduced mitotic ac-tivity and proliferation of trisomic cells, hasbeen proposed to be associated with thecharacteristic DS phenotype (Mittwoch,1972; Antonucci et al., 1997). This has beensupported by in vitro studies showing thatthe mitotic cycle of trisomic cells is longerthan that of normal cells, principally be-cause the G2 period of the cycle is increasedby approximately 3 hr compared with nor-mal (Paton et al., 1974). Other studies also

lend support to the notion of a growth retar-dation in trisomic cells, including investiga-tions indicating delayed cellular activityduring odontogenesis in trisomy 16 mice (DiStefano and Provenza, 1993), and thoseshowing a reduced number of cells in manybody organs of fetuses with Down syndrome(Naeye, 1967).

The critical stage of tooth developmentbegins around 4 weeks in utero with the for-mation of deciduous enamel organs and pro-liferation of the inner enamel epitheliumand concludes with mineralisation of thedental crowns (Nery et al., 1975). As calci-fication spreads in different directions to de-fine the future dentino-enamel junction,crown morphology is essentially determined(Dalhberg, 1971). Variations in growthrates of the different dimensions of forming

*Correspondence to: Professor Grant Townsend, DentalSchool, The University of Adelaide, South Australia 5005.E-mail: [email protected]

Received 14 December 2000; Revision received 28 March 2001;Accepted 16 April 2001

AMERICAN JOURNAL OF HUMAN BIOLOGY 13:690–698 (2001)

© 2001 Wiley-Liss, Inc.

PROD #M20089R

Page 2: Effect of Down syndrome on the dimensions of dental crowns and tissues

tooth crowns, therefore, tend to be reflect-ed in different final sizes and proportions(Peretz et al., 1997). Peretz et al. (1996, 1998)have shown that changes in molar size inDS tend to occur at an early stage of dentaldevelopment, whereas changes in shape oc-cur at a later stage of dental development.

Although microdontia of permanent toothcrowns in DS individuals is confirmed, it isnot known whether enamel and dentine areboth reduced proportionately or whetherthere is a differential effect. Reduced crownsize may be due to a reduction in enamelthickness, a reduction in the distance acrossthe dentino-enamel junction (so-called den-tine thickness), or a combination of both.Reduced enamel thickness reflects de-creased activity of secretory ameloblasts,whereas reduced dentine thickness reflectsdecreased proliferative activity of the cellsof the developing tooth germ (Alvesalo et al.,1991). There is evidence that deciduousteeth in DS are not reduced in size and thatthey may in fact be larger than normal(Townsend, 1983), but no information isavailable about enamel or dentine thicknessin these teeth.

This study, therefore, aimed to determinewhether the reported reduction in crownsize and altered crown shape of permanentmandibular incisors in DS individuals aredue to a proportional reduction in bothenamel and dentine thickness or whetherthe dimensions of these tissues are affecteddifferentially. The study also aimed toclarify how the trisomic condition affects de-ciduous dental dimensions. In addition, thedegree of variability of tooth size measure-ments and shape of incisor crowns in DSand non-DS individuals was investigated inorder to assess the level of stability of devel-opmental pathways and to clarify themechanisms involved in the formation ofthe DS phenotype which are still not wellunderstood (Reeves et al., 2001).

MATERIALS AND METHODS

Extracted permanent mandibular inci-sors and extracted/exfoliated deciduousmandibular incisors were investigated. TheDS sample comprised 61 teeth selected fromthe collection of Professor R.H. Brown andrepresented 48 DS patients of European an-cestry, 24 males and 24 females, living inmental institutions in New Zealand duringthe 1950s. The DS individuals were about 6to 30 years of age, and the permanent teeth

had been extracted mainly because of peri-odontitis. The non-DS sample comprised 55teeth, representing different individuals ofEuropean ancestry that were selected froma large collection of extracted teeth of un-known sex and age, housed at the AdelaideDental School. Only teeth without evidenceof gross caries, calculus, or wear that couldaffect the dental dimensions under consid-eration were included in the samples.

Maximum mesiodistal and labiolingualcrown dimensions of permanent and decidu-ous mandibular central and lateral incisorswere measured directly using Mitutoyo digi-tal callipers according to the method ofMoorrees et al. (1957). Replicate measure-ments were obtained from a sub-sample of40 teeth by the same investigator (E.B.) afew weeks after the initial measurementshad been obtained. Paired t-tests indicatedthat there was no significant systematic er-ror in measurement; none of the mean dif-ferences differed significantly from zero (P >0.05). The standard deviation of a single de-termination (Dahlberg, 1940) was calcu-lated to quantify the magnitude of randomerrors, with all values being less than0.1 mm.

Crowns were then sectioned midsagittallywith a motorized 1.5-mm stainless steel cut-ting blade and photographed under stan-dardised lighting conditions using a stereo-microscope (Wild-Lietz PhotomakroskopM400) with scale included. This enabled thelabial and lingual profiles of the toothcrowns to be examined as well as measure-ments of enamel and dentine thickness to beobtained. Measurements of enamel and den-tine thickness were made to the nearest0.01 mm at three reproducible locations oneach photograph. A line was drawn to jointhe labial and lingual cemento-enamel junc-tions, and then lines were constructed par-allel to this reference line at 1⁄4, 1⁄2, and 3⁄4 ofthe total crown height. Enamel and den-tine–pulp areas were computed after theiroutlines were digitised, and the length ofthe dentino-enamel junction (DEJ) was re-corded using a Kent curvimeter map mea-surer (Fig. 1).

The accuracy and reliability of the photo-graphic technique were confirmed by re-peating the whole procedure for 20 hemisec-tioned teeth and then comparing the secondmeasurements with those obtained on thefirst occasion and also with direct measure-ments. Paired t-tests indicated that all

DENTAL DIMENSIONS IN DOWN SYNDROME 691

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mean differences were non-significant (P >0.05), and standard deviations of a singledetermination were all less than 0.01 mm.

Tooth shape was assessed by calculatingratios of maximum mesiodistal:labiolingualcrown measurements and also by visual in-spection. In order to take account of toothsize when comparing enamel areas betweenthe DS and non-DS teeth, the ratio ofenamel area:length of the DEJ was calcu-lated, with the method of Martin (1985).

Preliminary comparisons of external orinternal dental measurements between DSmales and females using unpaired t-testsconfirmed that there were no significant sexdifferences (P > 0.05); the data for the sexeswere thus pooled for comparisons with thenon-DS sample. Previous studies have con-firmed that there is little evidence of sexualdimorphism in crown dimensions of DS andnon-DS mandibular incisors, supporting thedecision to pool the sexes for subsequentanalysis (Townsend, 1983). Mean values fortooth size variables were compared betweengroups using Student’s unpaired t-tests,and variances were compared using vari-ance ratio (F) tests. When correspondingteeth from both right and left sides wereavailable for either DS or non-DS individu-als, one side only was chosen at random forsubsequent comparisons between thegroups. Where a significant difference in

variability existed between the two groups,a modified t-test was used to determinewhether there was a significant differencein mean values between the samples. Thelevel of statistical significance was set at P <0.05.

RESULTS

Means, standard deviations, and rangesfor the external and internal tooth size vari-ables of permanent and deciduous mandibu-lar incisors in DS and non-DS samples arepresented in Tables 1–4.

Permanent mandibular centralincisors (Table 1)

No significant difference in mesiodistalcrown size was noted between DS and non-DS teeth, although the DS teeth showed sig-nificantly greater variability in this dimen-sion. DS teeth were significantly smaller inlabiolingual crown dimension than non-DSteeth, the percentage reduction beingaround 14%. The ratio of mesiodistal to la-biolingual crown dimensions was signifi-cantly greater in DS, reflecting their differ-ent shape compared to non-DS teeth.Average linear enamel and dentine thick-nesses were significantly smaller at allpoints of measurement in DS. Enamel areawas significantly smaller in DS by 38% andalso significantly more variable. Dentine-pulp area was also significantly smaller inDS by about 32%. When the influence oftooth size was taken into account, DS teethdisplayed significantly thinner enamel thannon-DS teeth. Figures 2 and 3 depict thelabiolingual crown profiles of a selected per-manent mandibular central incisors fromeach group, showing that DS teeth tended topresent a straight to almost concave labialprofile compared with the convex labialcrown profiles of non-DS teeth.

Permanent mandibular lateral incisors(Table 2)

Maximum mesiodistal and labiolingualcrown diameters of these teeth were signifi-cantly smaller, on average, in the DSsample compared with the non-DS sample(11% and 17% smaller, respectively). Theratio of mesiodistal to labiolingual crown di-

Fig. 1. Enamel and dentine thickness measurementswere obtained at three crown levels corresponding to 1⁄4,1⁄2, and 3⁄4 of the crown height. A line drawn between thecemento-enamel junction (CEJ) on the labial and lingualsurfaces of the crown served as a reference line. Totalenamel and dentine–pulp areas were also calculated, to-gether with the length of the dentino-enamel junction(DEJ).

692 E. BELL ET AL.

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mensions was significantly greater in DS,reflecting the different crown shape. Aver-age linear enamel and dentine thicknesseswere significantly smaller at all points ofmeasurement in DS. Both enamel and den-tine–pulp areas were significantly smallerin DS (37% and 39%, respectively) but sig-nificantly more variable. After correcting for

tooth size, the DS teeth displayed signifi-cantly thinner enamel. Figures 4 and 5 de-pict labiolingual crown profiles of a selectedpermanent mandibular lateral incisors fromeach group, showing again that the DSteeth tended to display a straight labial pro-file compared with the convex labial crownprofiles of non-DS teeth.

TABLE 1. Tooth size variables of permanent mandibular central incisors in DS and control subjects

Variable

Down syndrome(n 4 16)

Controls(n 4 15)

x̄ SD x̄ SDExternal measures

MD diam. (mm) 5.32 0.40b 5.31 0.25LL diam. (mm) 5.16a 0.30 5.99 0.28Ratio MD/LL 1.03a 0.08 0.89 0.06

Internal measures (mm)Labial enamel (¼) 0.30a 0.07b 0.41 0.04Labial enamel (½) 0.53a 0.08 0.70 0.09Labial enamel (¾) 0.60a 0.07 0.86 0.09Ling enamel (¼) 0.29a 0.08 0.37 0.05Ling enamel (½) 0.41a 0.08 0.47 0.07Ling enamel (¾) 0.42a 0.05 0.57 0.07Dentine (¼) 3.80a 0.37 4.74 0.23Dentine (½) 1.89a 0.36 2.45 0.39Dentine (¾) 0.57a 0.19 0.77 0.15

Enamel and dentine areasTotal enamel area (mm2) 6.22a 0.88c 10.12 0.25Total dentine–pulp area (mm2) 16.78a 1.87 24.84 1.35DEJ length (mm) 15.11a 0.75 18.62 0.85Enamel area/DEJ length (mm) 0.41a 0.05 0.54 0.03

aSignificant difference between mean values at P < 0.01.bSignificant difference between variances at P < 0.05.cSignificant difference between variances at P < 0.01.

TABLE 2. Tooth size variables of permanent mandibular lateral incisor tooth crowns in Down syndrome andcontrol subjects

Variable

Down syndrome(n 4 16)

Controls(n 4 15)

x̄ SD x̄ SDExternal measures

MD diam. (mm) 5.34b 0.45c 6.00 0.25LL diam. (mm) 5.22b 0.35 6.26 0.30Ratio MD/LL 1.02b 0.06 0.96 0.05

Internal Measures (mm)Labial enamel (¼) 0.34a 0.09 0.40 0.09Labial enamel (½) 0.56b 0.07 0.78 0.12Labial enamel (¾) 0.69b 0.07 0.96 0.09Ling enamel (¼) 0.33b 0.05 0.39 0.06Ling enamel (½) 0.39b 0.10 0.49 0.07Ling enamel (¾) 0.41b 0.07 0.57 0.07Dentine (¼) 4.00b 0.65 5.04 0.33Dentine (½) 1.91b 0.45 2.56 0.31Dentine (¾) 0.54b 0.17c 0.88 0.08

Enamel and dentine areasTotal enamel area (mm2) 6.90b 0.66d 11.02 0.31Total dentine–pulp area (mm2) 16.84b 3.16d 27.59 1.80DEJ length (mm) 14.40b 1.00 19.24 0.88Enamel area/DEJ length (mm) 0.48b 0.04 0.57 0.03

aSignificant difference between mean values at P < 0.05.bSignificant difference between mean values at P < 0.01.cSignificant difference between variances at P < 0.05.dSignificant difference between variances at P < 0.01.

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Deciduous mandibular central incisors(Table 3)

Maximum mesiodistal and labiolingualcrown dimensions of these teeth tended tobe larger in DS (2% and 11%, respectively).The crown size ratios of the two sam-ples were also significantly different al-

though in the opposite direction to thatnoted in the permanent teeth, i.e., the me-siodistal dimensions of the DS teeth tendedto be smaller than labiolingual dimensions.None of the linear enamel thickness mea-sures differed significantly between thegroups, but there were significant differ-ences between means and one of the vari-

TABLE 3. Tooth size variables of deciduous mandibular central incisor tooth crowns in Down syndrome andcontrol subjects

Variable

Down syndrome(n 4 16)

Controls(n 4 15)

x̄ SD x̄ SDExternal measures

MD diam. (mm) 4.08a 0.40 4.00 0.30LL diam. (mm) 4.24b 0.35 3.79 0.29Ratio MD/LL 0.96b 0.05 1.06 0.06

Internal measures (mm)Labial enamel (¼) 0.17 0.06 0.20 0.05Labial enamel (½) 0.29 0.09 0.30 0.09Labial enamel (¾) 0.35 0.12 0.37 0.10Ling enamel (¼) 0.16 0.04 0.14 0.05Ling enamel (½) 0.20 0.08 0.17 0.06Ling enamel (¾) 0.21 0.08 0.22 0.07Dentine (¼) 3.19a 0.32 3.38 0.19Dentine (½) 2.17a 0.21 1.99 0.17Dentine (¾) 1.04a 0.21c 0.86 0.11

Enamel and dentine areasTotal enamel area (mm2) 2.72 0.67 2.74 0.66Total dentine–pulp area (mm2) 11.19 1.99 10.05 1.16DEJ length (mm) 10.74 1.02 10.84 1.04Enamel area/DEJ length (mm) 0.25 0.07 0.25 0.04

aSignificant difference between mean values at P < 0.05.bSignificant difference between mean values at P < 0.01.cSignificant difference between variances at P < 0.05.

TABLE 4. Tooth size variables of deciduous mandibular lateral incisor tooth crowns in Down syndrome andcontrol subjects

Variable

Down syndrome(n 4 16)

Controls(n 4 15)

x̄ SD x̄ SDExternal measures

MD diam. (mm) 4.77 0.35 4.63 0.30LL diam. (mm) 4.25 0.33 4.20 0.22Ratio MD/LL 1.13 0.07c 1.10 0.04

Internal measures (mm)Labial enamel (¼) 0.19 0.06 0.23 0.04Labial enamel (½) 0.32 0.08 0.38 0.11Labial enamel (¾) 0.41a 0.13 0.55 0.16Ling enamel (¼) 0.14b 0.06 0.21 0.04Ling enamel (½) 0.20a 0.07 0.28 0.09Ling enamel (¾) 0.21 0.08 0.27 0.08Dentine (¼) 3.52 0.37 3.55 0.23Dentine (½) 2.13 0.22 2.07 0.18Dentine (¾) 1.00 0.36c 0.88 0.14

Enamel and dentine areasTotal enamel area (mm2) 2.93 0.58c 3.24 0.24Total dentine–pulp area (mm2) 11.80 1.68c 12.04 0.62DEJ length (mm) 10.89 1.02d 11.10 0.37Enamel area/DEJ length (mm) 0.27 0.06c 0.29 0.02

aSignificant difference between mean values at P < 0.05.bSignificant difference between mean values at P < 0.01.cSignificant difference between variances at P < 0.05.dSignificant difference between variances at P < 0.01.

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ances for dentine thickness. There was nosignificant difference in enamel area or den-tine–pulp area between DS and non-DSsamples.

Deciduous mandibular lateral incisors(Table 4)

Although values for average maximummesiodistal and labiolingual crown sizewere larger in DS (3% and 1%, respectively),the differences were not significant. The DSteeth also displayed greater variability inexternal crown measures, with the variancefor the crown ratio being significantlygreater in DS. Three linear enamel mea-sures differed significantly between thesamples, but dentine thickness did not dif-fer significantly between the DS and non-DS samples. Enamel area was not signifi-cantly different between DS and non-DSsamples, and dentine–pulp areas did notdiffer significantly between the two

samples. However, enamel and dentine ar-eas were significantly more variable in DS.

DISCUSSION

In developing incisor teeth, the spread ofcalcification from incisal to cervical regionsfixes the maximum mesiodistal crown di-mension at an early stage of formation be-cause this dimension is usually positionednear the incisal edge. In contrast, the maxi-mum labiolingual dimension, which is lo-cated near the cingulum in the cervical re-gion of the crown, is one of the lastcomponents of the crown to be permanentlyset. Assuming that the reported decrease inmitotic activity of cells in DS affects devel-oping tooth germs, one would expect thatlater determined dimensions of toothcrowns would be more reduced in size thanearlier determined dimensions. This is whatwas found in permanent mandibular inci-sors: the labiolingual dimensions of DScrowns were reduced in size to a greater ex-tent than the mesiodistal dimensions. Theresult of this differential reduction in sizewas that the crowns of permanent mandibu-lar incisors tended to be a different shape in

Fig. 2. Labiolingual crown profile of a selected perma-nent mandibular central incisors from a DS individual dis-playing straight to concave labial profile.

Fig. 3. Labiolingual crown profile of a selected perma-nent mandibular central incisors from a non-DS individualdisplaying a typical convex labial profile.

DENTAL DIMENSIONS IN DOWN SYNDROME 695

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DS; they were relatively broader mesiodis-tally but narrower labiolingually, the oppo-site relationship to normal. This findingbased on extracted DS teeth is consistentwith the results of an earlier study based ondental models (Townsend, 1983). Further-more, crown measures of DS permanent in-cisors tended to show greater variabilitythan those in the non-DS permanentsample, a result consistent with Shapiro’s(1975, 1983) contention that developmentalinstability is increased in DS associatedwith a disruption in homeostasis.

Although it has generally been assumedthat microdontia is characteristic of DS, thisstudy and previous investigations (e.g.,Barden, 1980; Townsend, 1983) confirmthat certain dimensions of deciduous teethin DS are similar in size to non-DS decidu-ous teeth or even larger. This suggests thatthe DS fetus may be relatively unaffected bythe triplicate dose of chromosome 21 duringthe first trimester of pregnancy, when thedeciduous teeth are undergoing criticalstages of odontogenesis. This is supportedby studies of general growth in DS fetusesthat have shown that growth retardation is

not evident until the second trimester(Kucera and Dolezalova, 1973; Globus,1978; Fitzsimmons et al., 1990). The levelsof variability for deciduous dental traitswere also similar between the DS and non-DS samples, suggesting that metabolic con-ditions may be more favourable during thecritical period of development of the decidu-ous incisors than later when the permanentteeth begin to form.

It has been suggested that there may be atransitory stage of acceleration in mitoticactivity of trisomic tooth germs during the8–10th weeks of fetal life that persists dur-ing the initial stages of mineralisation of thedeciduous teeth and is then followed by thecharacteristic retardation in growth(Barden, 1980). While this explanation can-not be discounted, another possibility is thatthe findings for deciduous incisors may rep-resent a sampling effect (Townsend, 1983).The teeth available for study in this inves-tigation were collected from DS individualswho had survived to reach childhood orearly adulthood. Given that DS is associatedwith an increased mortality rate, estimatesof spontaneous abortion ranging from 24%

Fig. 4. Labiolingual crown profile of a selected perma-nent mandibular lateral incisor from a DS individual dis-playing a straight labial profile.

Fig. 5. Labiolingual crown profile of a selected perma-nent mandibular lateral incisor from a non-DS individualdisplaying a typical convex labial profile.

696 E. BELL ET AL.

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to 65% (Creasy and Crolla, 1974; Hook,1978), the teeth that we measured were rep-resentative of survivors or the fitter DS in-dividuals. One could hypothesise that theseindividuals might have experienced lessgrowth retardation than those who failed tosurvive, and this could then be reflected intheir dentitions, particularly their earlyforming deciduous teeth.

Results of the metric analyses of perma-nent mandibular incisors from DS individu-als indicate that growth retardation and re-duction in mitotic activity of trisomic cellsmay commence in the second trimester ofpregnancy and continue thereafter. This isthe period of time when the crowns of thepermanent teeth are forming. The finding ofa reduction in tooth size in permanent man-dibular incisors in DS compared with non-DS permanent teeth is consistent with pre-vious investigations (Barden, 1980;Townsend and Brown, 1983). Enamel anddentine were both responsible for the labio-lingual size reduction, reflecting altered ac-tivity of ameloblasts and odontoblasts andprobably their progenitor cells. The findingsare also consistent with those of Zilberman(2000), who compared enamel and dentinethickness of permanent first molars and de-ciduous second molars between DS and non-DS individuals using radiographs. Enamelheight and width, as well as dentine thick-ness, were reduced in DS, indicating thatthe trisomic condition influenced both ecto-dermal and mesenchymal tissues.

We propose that there is a decrease in mi-totic activity (proliferation) of trisomic cellsin developing permanent tooth germs thatproduces a smaller number of ecto-mesenchymal cells needed to create dentine.Because dentine forms the bulk of the den-tal crown, a decrease in mitotic activityseems logical as the main reason for micro-dontia of permanent incisors in DS indi-viduals. It is also likely that there would befewer inner enamel epithelial cells at theDEJ to differentiate into ameloblasts andsecrete enamel matrix. Indeed, after adjust-ments were made for the influence of toothsize, enamel was significantly thinner in thepermanent incisors of DS individuals, indi-cating that the secretory activity of amelo-blasts is reduced.

The differences observed in crown profilesof permanent incisors between DS and non-DS individuals suggest that the activity ofcells contributing to the inner enamel epi-

thelium may be altered at the time that theDEJ is forming. There was no clear trend forthe enamel to be differentially reduced inthickness in the middle or cervical regionsof the crown, so the straighter labial profilesof DS permanent incisors would seem to re-flect a decreased curvature of the labial as-pect of the inner enamel epithelium. Thismay be due to fewer cells in the internalenamel epithelium of DS teeth resultingfrom a decrease in mitotic activity.

The trend for increased variability oftooth size measurements in incisors fromDS individuals is consistent with the con-cept that homeostasis is disrupted in thecondition. Shapiro (1975) showed that thosepalatal and dermatoglyphic features thathave most environmental variance in nor-mal individuals were most deviant in DSand proposed that a generalized decrease indevelopmental homeostasis occurred in DS.It was termed amplified developmental in-stability. No clear trend was noted in thepresent study for certain dental dimensionsto display greater variability in DS thanothers, although maximum mesiodistal di-ameters were significantly more variable intwo of four comparisons and total enamelareas were significantly more variable inthree of four comparisons. Further studiesare required to clarify whether there is adifferential effect on variability of dental di-mensions in DS.

CONCLUSION

Information gained through this study ofmandibular incisors in individuals withDown syndrome indicates that there is a re-duction in cellular activity during the pro-liferative and secretory phases of odonto-genesis in the second trimester of fetal life.Reduced mitosis leads to a generalised re-tardation in growth, evidenced by thesmaller size of permanent tooth crowns inindividuals with Down syndrome. In addi-tion, differences in crown proportions andprofiles are evident. The deciduous teeththat form earlier on seem to be relativelyprotected from these size-reducing effects.Increased variability for dental dimensionsobserved in DS is consistent with the con-cept that widespread physiological pertur-bation throughout the body leads to devel-opmental disharmony and instability in thephenotype of individuals with Down syn-drome.

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ACKNOWLEDGMENTS

The support of the National Health andMedical Research Council (NHMRC) in theform of a Dental Undergraduate Scholar-ship to E.J.B. is gratefully acknowledged.The teeth of the Down syndrome childrenwere collected by Professor Harvey Brown,and we thank him for allowing us access tothis valuable collection.

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