craniofacial patterning in klinefelter (47 xxy) adults

European Journal of Orlhodoitllcs IS 0993) 183-194 © 1993 European Orthodontic Society

Craniofacial patterning in Klinefelter (47 XXY) adults

T. Brown*, L Alvesalo**, and G. C. Townsend*'Department of Dentistry, The University of Adelaide, South Australia, and "Institute of Dentistry,University of Oulu, Finland

SUMMARY Radiographic cephalometry incorporating a pattern profile analysis was used tocompare 26 adult Klinefelter males from Finland with first degree adult relatives, 15 males and14 females. Compared with female relatives, the 47 XXY males were larger in almost allcraniofacial linear dimensions, but were similar in facial shape apart from greater mandibularprognathism. Mandibular dimensions in particular differed between the Klinefelter and unaffectedmales, the corpus length being larger, the ramus shorter and the gonial angle more obtuse inthe 47 XXY group. The prominent facial profile, most marked in the mandible, was a dominantfeature of the Klinefelter subjects who also displayed a more acute median cranial base anglethan each control group. Generally, Klinefelter morphology was marked by greater variability orpatterning of the craniofacial structures compared with relatives, possibly due to decreaseddevelopmental canalization. It is proposed that the 47 XXY complex may affect endochondralgrowth in the cranial base, as well as having a direct influence on jaw growth.

Introduction

The syndrome described by Klinefelter et al.(1942) is characterized primarily by hypogonad-ism, gynaecomastia, aspermatogenesis, andsometimes a lowered Leydig cell function.Several male karyotypes with additional Xchromosomes may show similar clinical signsbut true Klinefelter syndrome, with a 47 XXYkaryotype, is confirmed by cytogenetic examina-tion. The syndrome occurs with a frequency ofabout 1 in 500 males and approximately 80 percent of subjects showing the clinical signs havethe 47 XXY karyotype (Klinefelter, 1984;Perwein, 1984). An extensive literature on theclinical, genetic and psychological aspects ofKlinefelter syndrome has accumulated withcomprehensive reviews provided by Bandmannand Breit (1984), and Serensen (1988).

The facial appearance of 47 XXY subjectswas described by Gorlin et al. (1965) who drewattention to the shallow palate and relativemandibular prognathism. A cephalometricstudy of 36 Danish adults with Klinefeltersyndrome was reported by Ingerslev and Krei-borg (1978). In comparisons with 102 normalyoung adult Danish males, the Klinefeltersubjects displayed several distinctive character-istics, namely a smaller calvaria, increasedcranial base flexion, larger gonial angle andmore pronounced maxillary and mandibular

prognathism. When compared graphically withfemale controls, the Klinefelter males weresimilar in calvarial size, but larger in overallsize of the jaws. The authors suggested thatthe increased prognathism of the Klinefeltersubjects might be related to shape of the cranialbase.

Twenty-two adult Klinefelter males werecompared by radiographic cephalometry with28 male and 49 female young adults, all subjectsfrom Belgrade (Babic et al., 1991). On the basisof significant decreases in the size of the anteriorcranial base, face heights and mandibular ramusin Klinefelter subjects compared with normalmales, the authors suggested that the extra Xchromosome reduced craniofacial growth.However, all linear dimensions, apart frommaxillary length, were greater in the Klinefeltergroup than in normal females.

It is noteworthy that further recent resultsclearly indicate that mesial molar occlusion wasa relatively frequent occlusal anomaly in Kline-felter syndrome men (Alvesalo and Laine,1992).

Tooth crown size characteristics of the syn-drome and other sex chromosome aneuploidieswere discussed by Alvesalo (1985) and Town-send et al. (1988). For example, reductions inmesiodistal and buccolingual diameters of per-manent teeth by 6.1 and 2.6 per cent, respect-

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186 T. BROWN ET AL.

ively, were demonstrated in Turner syndrome.In contrast, Klinefelter males showed a 1.8 and1.7 per cent increase in the respective toothdiameters. There appeared to be direct butdifferential effects of X and Y chromosomeson tooth development. Crown size was generallyincreased by additional X or Y chromosomesand reduced by loss of these chromosomes, butthe relative proportions of enamel and dentinediffered depending on the chromosome.

General physical growth is also affected inKlinefelter syndrome. Serensen (1988) foundthat five Klinefelter boys, examined from age3 to 10 years, were approximately 5 cm tallerthan normal male children at each age. Afurther 16 Klinefelter school-boys were signi-ficantly taller than controls from 7 to 15 years.The observed height increase, however, waspredominantly in leg length relative to upperbody segment, a trend that was present beforepuberty. The aberrant growth patterns in chil-dren with abnormalities of the sex chromosomesmight be due to interference with commonmechanisms of growth control according toMiller et al. (1980). This abnormality, theysuggested, might result from a change insensitivity of the growth mechanism or fromprenatal gonadal dysfunction and altered endo-crine control.

As little is known of the craniofacial charac-ters of Klinefelter males from other populations,or the morphological relationships betweenKlinefelter subjects and unaffected members oftheir families, the present study of Finnishindividuals was carried out. The sample of47 XXY subjects was augmented by recordsfrom" a number of first degree relatives —parents, brothers and sisters. The analysis islimited to adult members of the study popu-lation.

Subjects and methods

The study was part of a larger investigation ofdental and craniofacial growth and develop-ment, oral health, and anthropometries inFinnish individuals with various sex chromo-some anomalies and their families. Up-to-date313 patients and 371 first-degree relatives havebeen examined. Cytogenetic confirmation ofKlinefelter patients had been made from bloodsamples taken for medical purposes prior to

the dental project. The propositi were ascer-tained through hospitals, cytogenetic units, orthe doctors involved. Hormonal therapy, whenrequired, was usually administered atadulthood.

Standardized lateral head radiographs ofKlinefelter males and their family memberswere examined. However, radiographs wereexcluded if the imaging of important referencepoints was inadequate for their unambiguouslocation, if either jaw was edentulous, or if thedentition was impaired by missing teeth orrestorative procedures to such an extent thatthe position of intercuspal occlusion wasdoubtful.

Radiographs of 40 subjects with Klinefeltersyndrome, who ranged in age from 5 to 58years, were selected for cephalometric analysis.First degree relatives represented by acceptableradiographs totalled 33, comprising 6 fathers,11 brothers, 6 mothers, and 10 sisters. Of the40 Klinefelter subjects, 22 had one relativerepresented, four had two relatives and onehad three relatives; radiographs were either notavailable or unsuitable for any relatives of theremaining 13 Klinefelter subjects.

A subset of 26 lateral head radiographs wasretained for tracing and measurement to repres-ent adult Klinefelter males aged 18-58 yearsand averaging 31 years. Male relatives wererepresented by seven fathers and eight brothers,aged 18-67 years and averaging 37 years. Forthe female relatives, radiographs representingsix mothers and eight sisters, aged 26-51 yearsand averaging 36 years were suitable. Theseadult relatives were accepted for the purposesof the present comparison as the normal Finnishcontrol group.

Pattern Profile Analysis (PPA) as describedby Gam et al. (1984) was the main system forcephalometric analysis. Our implementation ofPPA requires the measurement of 16 key lineardistances representing features of the cranialvault, facial heights and facial depths. Thereference points and variables used in PPA areshown in Figs 1 and 2 and Table 1. A patternprofile is calculated for each subject byexpressing the variables as standard deviatescores, that is z-scores, in relation to a popula-tion standard. For this purpose Gam el al.(1984) used standards calculated from subjectsof the Ann Arbor, Michigan, Growth Study,


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CRANIOFACIAL PATTERN OF KLINEFELTER MALES 187

Figure 1 Cephalometric reference points: 1, gnathion (gn);2, infradentale (id); 3, prosthion (pr); 4, spinal point (sp);5, nasion (n); 6, glabella (gl); 7, sella (s); 8, opisthion (op);9, condylion (cd); 10, condyle-nasion point (cd-n); 11,posterior nasal spine (pns); 12, upper molar cemento-enamel junction (udj); 13, upper alveolar point (uap); 14,lower molar cemento-enamel junction (ldj); 15, mandibularplane point (mp); 16, tangent gonion (tgo); 17, coronoidprocess (cp); 18, incision superius (is); 19, apex superius(as);20, incision inferius (ii); 21, apex inferius (ai); 22, subspinale(ss); 23, supramentale (sm); 24, pogonion (pg); 25, progna-thion (pgn); 26, basion (ba); 27, articulare (ar). Fordefinitions see Gam el al. (1984), and Brown and Travan(1988).

Figure 2 Linear dimensions used in pattern profile analysisand defined in Table 1.

using a larger sample than reported by Rioloet al. (1974). In the present analysis, however,the respective means and standard deviationscomputed for the normal Finnish controls weresubstituted. An index of pattern variability,

calculated as the standard deviation of the 16z-scores, was also derived for each subject. Thisindex, according to Gam et al. (1985), servesas a useful indicator of the extent of craniofacialvariability, the median index for a normalpopulation being around 0.8.

An expanded version of the semi-automaticcomputer-driven program described by Brownand Travan (1988) was used to calculate therequired linear distances from the digitized co-ordinates of reference points. Automatic com-pensation for radiographic enlargement, estim-ated to be 8.7 per cent for structures locatedin the median sagittal plane, was carried out.

To supplement the PPA, the additional 22variables also listed in Table 1 were computedfrom the co-ordinates of the reference pointsdelineating them. These variables were selectedto describe regions not adequately covered bythe standard PPA — the facial profile, dimen-sions and inclinations of the jaws, anterior faceheights, and cranial base.

Double determination evaluations were car-ried out on 20 radiographs selected at randomfor repeat tracing and digitizing. Experimentalerrors were assessed by calculating the distribu-tions of the differences between first and seconddeterminations of the variable scores, and byestimating the standard deviations of singledeterminations after the method of Dahlberg(1940).

For the 16 linear distances included in thePPA, the absolute mean differences betweendeterminations ranged from 0.06 to 1.22 mmand averaged 0.42 mm; only two of these meandifferences were statistically significant at the/><0.05 level. The standard deviations of singledeterminations ranged from 0.41 to 2.41 mm,averaging 1.18 mm. Differences between deter-minations for the additional 22 variables,ranged from 0.01 to 0.99 mm or degrees,averaging 0.27, and the standard deviations ofsingle determinations ranged from 0.49 to1.65 mm or degrees averaging 1.00.

Generally, the effect of experimental erroron mean values was small and the standarddeviations of single determinations were lessthan 1.25 mm or degrees for all except 10 ofthe 38 variables. Although the medial andlateral cranial base angles, n-s-ba and n-s-ar,were subject to the largest experimental errors,probably due to poor radiographic imaging inthe region, they were retained because of the


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188 T. BROWN ET AL.

Table 1 Variables used for cephalometric analysis.

A. Pattern profilePSTSASSNFDPLSRMCRHMHSHAHADGSPFSF

B. Supplementarys-n-sps-n-sss-n-prs-n-ids-n-sms-n-pgss-n-sm

ss-pmpm-baar-tgopg-tgoML/NSLCL/MLRL/ML

n-gnsp-gnn-bas-bas-arn-arn-s-ban-s-ar

Variable

analysisPosterior skull base lengthTotal skull base lengthAnterior skull base lengthSella-nasionFacial depthPalatal lengthSuperior ramus lengthMandibular corpus lengthRamus heightMandibular heightSymphyseal heightAlveolar heightAnterior dental heightGonion-scllaPosterior face heightSuperior face height

analysisMaxillary prognathismMaxillary basal prognatrusmMaxillary alveolar prognathismMandibular alveolar prognathismMandibular basal prognathismMandibular prognathismBasal jaw relationship

Maxillary basal lengthPharyngeal depthRamus heightCorpus lengthMandibular inclinationChin angleGonial angle

Total face heightLower face heightMedial cranial base lengthPosterior medial cranial base lengthPosterior lateral cranial base lengthLateral cranial base lengthMedial cranial base angleLateral cranial base angle

Reference points

8-78-67-67-59-54-119-171-169-16

14-151-23-42-3

16-712-104-5

7-5-47-5-227-5-37-5-27-5-237-5-24

22-5-23

22-1111-2627-1624-16

1-16/5-72-24/1-16

27-16/1-16

5-14-15-267-267-275-275-7-265-7-27

interest shown in the cranial base by previousinvestigators of the chromosomal aneuploidies.

Results

Results of the PPA and supplementary analysisfor Finnish Klinefelter adults and the adultcontrols are listed in Table 2 and illustrated bycomputer plots in Figs 3 and 4. The averagelinear dimensions in the Klinefelter group weregreater than the corresponding values for thefemales, all but two of the differences in means

being significant. Apart from mandibular pro-gnathism which was significantly more pro-nounced in the syndrome subjects, there werefew contrasts in facial shape between theKlinefelter and female groups.

When compared with the male controls byPPA, the Klinefelter individuals displayed ageneral similarity in craniofacial size with themajority of the mean values falling betweenthose of the male and female controls. Themost striking feature of the Klinefelter malesresided in the mandible which was significantly


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Table 2 Comparison of Finnish KJinefelter adults and controls. Sample sizes are 26 for Klinefelter,15 for male relatives, and 14 for female relatives except where indicated.

Variable

A. Pattern profileAge

PSTSASSNFDPLSRMCRHMHSHAHADGSPFSF

B. Supplementarys-n-sps-n-sss-n-prs-n-ids-n-sms-n-pgss-n-sm

ss-pmpm-baar-tgopg-tgoML/NSLCL/MLRL/ML

n-gnsp-gnn-bas-bas-arn-arn-s-ban-s-ar

Klinefelter

Mean

analysis30.98

76.66151.5577.2870.2586.1454.0337.2976.5661.2324.142

31.9216.0021.4182.3456.063

51.62

analysis90.9086.3289.2086.7785.1084.45

1.23

50.1847.0451.0681.3628.47 •70.57

123.22

J 18.6268.38

105.65 '47.0635.0393.10

127.73120.35

SD

8.41

2.894.583.303.364.233.093.265.724.413.332.763.271.985.504.353.36

4.774.584.794.995.065.123.40

2.733.894.165.967.057.026.99

6.78. 5.77

4.283.083.594.526.225.68

Male relatives

Mean

37.44

76.391

151.931

77.7470.3587.9453.2637.2571.30*63.9625.7232.1417.0321.8187.04*54.7852.11

87.9882.81*86.35*82.15**80.45**81.88"2.36

48.7044.10**53.99*76.19*27.8571.18

121.51

120.8170.21

104.3345.8037.4195.53

126.78122.03

SD

13.60

3.279.522.802.883.224.883.526.654.792.812.502.632.555.243.982.95

5.023.793.233.062.912.913.56

3.602.414.207.305.096.778.18

7.315.674.072.852.603.794.554.39

Female relatives

Mean

35.87

71.16**142.59**72.72**65.80**82.35*49.97**35.6466.80**55.05**22.20*28.64**14.8320.16*74.41**49.00**47.35**

88.1083.0186.0981.96"79.90"80.91*

3.11

45.93"43.77*45.96**72.08**30.0872.68

123.17

108.60**62.89**98 .41"41.49**32.78*88.69**

132.19*125.22*

SD

7.48

3.445.292.733.114.273.182.883.895.501.622.552.261.366.623.303.03

6.636.805.824.734.985.352.96

3.572.515.224.147.574.775.73

4.463.543.742.422.714.125.916.43

'Observations for male relatives= 14.2 Observations for Klinefelter subjects = 25.Observations for Klinefelter subjects = 24.*Mean value differs significantly from Klinefelter mean at P<0.05."Mean value differs significantly from KJinefelter mean at /><0.01.

larger in corpus length, but shorter in gonion-sella length (P<0.05). Ramus, mandibular, andsymphysis heights of the mandible, RH, MH,and SH, were also smaller in the Klinefelter

group, but the differences were not statisticallysignificant. Average posterior facial height (PF)was greater and superior facial height (SF)shorter in the Klinefelter subjects. Dimensions


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190 T. BROWN ET AL.

-FEMALE RELATIVES-KLINEFELTER-MALE RELATIVES

Figure 3 Average craniofacial polygons of Klinefeltermales and relatives.

4-

3-

2-

u ooi

-2

-3

-4 I DEPTHS 1 , HEIGHT9[SKULL G FACE) , MANDIBLE , , FACEH—I—I—t—t—I—I—I—I—I—I—I—I—I—I—I-

VARIABLE

Figure 4 Pattern profile of z-scores for Klinefelter males

of the cranial vault and base, PS, TS, AS, andSN were almost identical in the syndrome andcontrol groups.

The supplementary analysis indicated thatKlinefelter subjects were more prominent in thefacial profile relative to the cranial base thanboth male and female controls, the groupdifferences in mean values extending to about5 degrees for the angle of mandibular basalprognathism, s-n-sm. Most of the differencesin the mean angles of facial prognathism werestatistically significant. As a consequence of therelative mandibular prognathism, the angle ofsagittal jaw relation, ss-n-sm, was smallest inthe Klinefelter males.

With respect to the remaining variables, otherfeatures of Klinefelter craniofacial morphologycompared with that of the male relativesincluded the deeper nasopharynx, pm-ba;shorter mandibular ramus, ar-tgo; longer man-dibular body, pg-tgo; wider gonial angle, RL/ML; and slightly shorter anterior face heights,n-gn, and sp-gn. There were no significantdifferences in the cranial base dimensionsalthough the lengths, s-ar and n-ar wereslightly shorter in the Klinefelter subjects. Themedial and lateral cranial base angles weremore acute in the Klinefelter males than intheir female relatives, the differences in meanvalues being statistically significant at P<0.05.However, the Klinefelter subjects did not differgreatly from their male relatives in mean valuesfor these angles.

It is interesting to note that the craniofacialpattern in the Finnish Klinefelter males wassimilar to that described in the Danish Kline-felter group by Ingerslev and Kreiborg (1978).Of the 18 variables common to each study,only three displayed statistically significantdifferences in mean values. These were thelinear distances pharyngeal depth, pm-ba,sella-nasion, SN, and posterior medial cranialbase length, s-ba all of which were all about2 mm greater, on average, in the Finnish group.

Table 3 summarizes intra-family comparisonsfor the PPA. The indices of pattern variabilitydiffered between the 47 XXY subjects and theirrelatives. Klinefelter males displayed indicesranging from 0.76 to 1.62, averaging 1.12,whereas the male relatives ranged from 0.60 to1.12, averaging 0.76, and the female relativesranged from 0.72 to 1.29, averaging 1.04, forthe variability index. Five of the 16 Klinefelterindividuals had a lower index than his relative,but in two of these instances the difference inindex values was small. For the remainingcomparisons, the pattern variability index wasclearly greater in the Klinefelter subject con-firming the impression gained from examiningKlinefelter radiographs that craniofacial mor-phology tended to be more highly patterned orvariable in the syndrome subjects than in theunaffected relatives. However, only in six47 XXY males did the pattern variability indexexceed the value of 1.20 suggested by Garnet al. (1985) to be the upper limit of normalvariability.

With respect to the morphological similarities


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Table 3 Craniofacial patterning in Klinefelter subjects and first-degree relatives.

Klinefeltersubject

K03K07K09K16K32K33K34K36K39

Average index

K02K06K14K15K17K18K28

Average index

Age

291937322858292638

36182034413827

Variabilityindex

1.080.911.150.621.261.500.950.760.89

1.01

1.221.341.421.271.620.791.07

1.25

Relative

fatherbrotherbrotherbrotherfatherbrotherbrotherbrotherbrother

sistermothersistersistersistersistersister

Age

682029344856311839

51452639314231

Variabilityindex

0.910.600.600.650.730.831.120.790.61

0.76

1.010.921.290.940.721.121.29

1.04

Correlationcoefficient

0.290.450.670.680.860.020.670.840.55

0.420.440.450.090.45

' 0.580.57

between the Klinefelter subjects and theirrelatives, the correlations were moderate formost pairs, the average coefficients, by z-transformation, being 0.61 and 0.44, respect-ively, for male and female relatives. It isinteresting that Brook et al. (1977) reportedcorrelation coefficients between, mid-parentaland offspring stature measured in adult Turnerand Klinefelter subjects, and their parents of0.61 and 0.62, respectively.

Figure 5 illustrates family associationsrevealed by a PPA of a 28-year-old Klinefeltersubject and his 48-year-old father. For thiscomparison, the pattern profiles were relatedto the North American standards from AnnArbor reported by Gam et al. (1984). Thesyndrome characteristics are well-displayedhere: mandibular prognathism, altered mandib-ular shape and shorter anterior facial heights.The family similarities, however, are evident inthe z-score pattern profiles which tend to beapproximately parallel even though they differin z-score values.

Discussion

Compared with the unaffected male and femalecontrols, the Klinefelter subjects tended to bemore variable in craniofacial build, which mayreflect decreased developmental canalization

due to the unbalanced chromosome constitu-tion. Craniofacial pattern was particularly dis-tinctive in the mandible which, on average,displayed a shorter ramus, longer body, largergonial angle, and greater prognathism relativeto the maxilla and cranial base. Although therewas a tendency towards a reduction in faceheights, the other size differences between theKlinefelter and normal males were smaller and,in the main, statistically non-significant. TheKlinefelter males, however, were larger in alllinear dimensions than the female controls.

Previous reports of the craniofacial character-istics of Klinefelter syndrome also includedreference to the mandibular prominence. Forexample, Gorlin et al. (1965) summarizeddescriptions of the facial appearance found invarious chromosomal aneuploidies pointing outthat with additional X chromosomes the palatetended to become progressively shallower andthe mandible more prognathic in relation tomaxilla and cranial base.

Ingerslev and Kreiborg (1978), in theircephalometric study of Danish 47 XXY sub-jects, drew attention to morphological featuresadditional to the increased prognathism, namelya smaller calvaria, smaller cranial base angle,and larger gonial angle. The size of the calvariaappeared to be similar in the Finnish Klinefelterand control groups, but in the absence of more


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192 T. BROWN ET AL.

KJ2

I 06PTKS 1 i HEIGHTS| SKULL C FACEi i MANDIBLE i i FACE

K12

K12F Z-SCORES: SUBJECTS 1 TO 2

1K32M

28.501.81

.2K32F

H48.271.11

SUBJECT:REG:SEX:AGE:SD-Z:

1 POST. SKULL BASE2 TOTAL SKULL BASE3 ANT. SKULL BASE4 SELLA-NASION5 FACIAL-OEPTH6 PALATAL-LENGTH7 SUPERIOH-RAKUSB HANDIBULAR-CORPUS

9 HAMUS-HEIGHT10 HANDIBULAR-HEI6HT11 SYHPHYSEAL-HEISHT12 ALVEOLAH-HEIGHT13 ANT. DENT. HEIGHT14 GOMON-SELLA13 POST. FAC. HEIGHT16 SUP. FAC. HEIGHT

1234587891011121314ISIE

PSTSASSNFDPLSP.HCBHHHSHAHAOGSPFSF

1.1.0.

-1.-0.-0.1.0._o-2

1B354100463762BBO66.07

-2.01-300-2-1

.31

.87

.82

.01

.68

1.

_o0-1100-1-0-101

-0-0

266.27OB.95.77.40.82.39.75.07.56.91.61.31.46.27

Figure 5z-scores.

Comparison of KJinefelter male K.32 and father K32F showing craniofacial polygons and pattern profile of

comprehensive measurement data this couldnot be verified. Whereas the Danish Klinefeltermales displayed a gonial angle that was, onaverage, 5 degrees larger than normal, the anglewas only about 2 degrees larger in the FinnishKlinefelter males.

Observations of cranial base flexion in Kline-felter syndrome are interesting in the light ofprevious reports. For example, Ingerslev andKreiborg (1978) found an increase in flexionof over 3 degrees for both medial and lateralcranial base angles in the Danish Klinefeltermales compared with normal males. In theKlinefelter males from Belgrade, Babic et al.(1991) found that the medial cranial base anglewas reduced by over 6 degrees when comparedwith normal males and females. The Finnishand Danish males were almost identical inflexion of the cranial base, the average medialand lateral angles differing by less than 1 degreebetween groups. Although the cranial baseangles were considerable smaller, by almost 5degrees, in the Finnish Klinefelter males com-

pared with female controls, this was not thecase with male controls who were similar tothe Klinefelter subjects in medial cranial baseangle and only 2 degrees larger in lateral cranialbase.

This finding of similar cranial base flexionin the Klinefelter males and the male relativeswas unexpected as it did not parallel theobservations in the other populations referredto above. Small sample sizes, particularly forthe relatives, combined with relatively largeerrors of measurement would have affected thereliability of the values for the Finnish subjects.Alternatively, there may be a familial basis forthe observed similarity in cranial base. As thisreport is the first cephalometric study ofcraniofacial morphology in relatives of Kline-felter males, further clarification of cranial baserelationships must await additional data.

The developmental events underlying thecraniofacial pattern in Klinefelter syndrome arenot yet completely understood although withincreasing evidence from studies of this and


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other chromosomal aneuploidies interestingtrends are emerging. Ingerslev and Kreiborg(1978) suggested that the maxillary and mandib-ular prognathism observed in the Danish Kline-felter males might be due to the altered sizeand shape of the cranial base rather thanmorphological differences in size and positionof the jaws. While these associations werecertainly present, a causative relationship is notcertain. In the Danish and Finnish Klinefeltergroups, the altered mandibular shape andtendency towards shorter face heights andincreased facial depths, particularly in the lowerface, appear to be important determinants ofthe anterior prognathism. In the light of theobservations from the Finnish subjects, it islikely that the size and shape of the facialstructures were major contributors to the char-acteristic lower facial prominence of Klinefeltersyndrome. Certainly, these appear to be equallyas important as any regional change in thecranial base shape. Although this report dealswith adult subjects, the characteristic facialappearance was also noted in the pre-adolescentKlinefelter boys available for analysis leadingto the view that the increased mandibularprognathism was not solely related to growthevents and hormonal changes taking placearound adolescence, if at all.

Recent cephalometric analyses of Turnersyndrome females by Jensen (1985) and Pelto-maki et al. (1989) have thrown further light onpossible relationships between X chromosomeaneuploidy and craniofacial morphology. Inthe first of these, 41 Danish 45 X individualswere compared with 51 normal adult Danishwomen. In the syndrome subjects, the calvariaand jaws were small, the cranial bases wereshorter and flatter, and both the maxillae andmandibles were retrognathic.

In the second study Peltomaki et al. (1989)compared Finnish 45 X women with first-degree female relatives and controls, findingthat the syndrome women displayed a shortenedcranial base clivus and a flatter cranial baseangle. In addition, although the face wasretrognathic it was not rotated posteriorly. Themandible was shorter in the Turner subjects,but the size of the calvaria was similar to thatof normal women. The results from Finlandsupported the view of Jensen (1985) that thecranial base in particular was affected in theTurner syndrome women and that the other

facial features apparently were partly a con-sequence of the primary cranial base morpho-logy. The Finnish authors suggested thatretarded cartilaginous growth might be thedevelopmental disorder responsible • for theobserved cranial base configuration.

Considering the results from the cephalo-metric analyses of Turner and Klinefelter syn-dromes collectively together with those of thenormal relatives, there is no doubt that loss oraddition of X chromosomes affects craniofacialmorphology. The consequence of the particularform of aneuploidy is most obvious in thelateral facial profile which displays increasingrelative mandibular prognathism in a progress-ive sequence from the 45 X through 46 XX,46 XY to 47 XXY genotypes. The work ofGorlin et al. (1965) referred to above suggeststhat this trend continues with an increase inthe number of X chromosomes beyond thatfound in true Klinefelter syndrome. Generally,compared to normal males the additional Xchromosome in Klinefelter syndrome appearsto have a slightly depressing effect on lineargrowth of the face except for some depthdimensions, for example, mandibular corpuslength, which are enhanced. On the other hand,compared to normal females, the additional Ychromosome in Klinefelter males has an enhan-cing effect on facial growth, increasing all lineardimensions.

The precise way in which the XXY chromo-some complex affects craniofacial growth,including the possible role of hormones, andthe time of onset and duration of the disturb-ances are, however, conjectural. While it islikely that the cranial base is affected, possiblythrough interference with endochondral growthactivity at the spheno-occipital synchrondrosis,a direct influence on the jaws appears to beinvolved as well. The changes in facial andmandibular dimensions, and the resulting effecton shape of the mandible and sagittal jawrelationships could also arise from a disturbanceto cartilaginous or membranous growth of thefacial skeleton. Additional investigations ofvarious chromosome anomalies are needed forfurther clarification of the role of sex chromo-somes in craniofacial growth and to determinehow the alteration in facial morphology isassociated with a more generalized growthdisturbance.


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Address for correspondence

Emeritus Professor T. BrownDepartment of DentistryThe University of AdelaideGPO Box 498AdelaideSouth Australia 5001

Acknowledgements

We acknowledge with gratitude financial sup-port for the study from the Academy of Finlandand The University of Adelaide.

References

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