Differences in the Eruption Angle of Palatally Displaced Canines in Klinefelter Syndrome: a Retrospective Study on Panoramic Radiographs.

OBJECTIVE: To investigate the eruption angle of maxillary canine in patients with Klinefelter syndrome (KS) in which high prevalence of palatally displaced canine anomaly (PDC) has been found by clinical assessment. SUBJECTS AND METHODS: The sample consisted of 37 KS males aged 20-34 years (mean 27 years) and the control group which consisted of 78 healthy males aged 20-27 years (mean 23 years). A pioneer method was used to measure the eruption angle. It was based on determining the topographic construction of mandibular gonion line called GO-GO method on panoramic radiograph.
RESULTS: The mean of eruption angle was increased for 10.58° in the right side and 9.69 ° in left side in patients with KS compared to those in the control group. The difference of mesioangular inclination of palatally displaced canines in Klinefelter patients was statistically significant (p< 0.01). When eruption angle in the control group was compared to Klinefelter patients, the statistical difference was confirmed for respective sides (P <0.01 for both).
CONCLUSIONS: The difference between eruption angle values in KS patients as well as in those belonging to the control group seemed to identify a developmental disturbance, thus confirming the fact that an extra X chromosome has an influence. The GO-GO method might be used for males when it is difficult to define occlusal planes, or for comparison. If this method is used, the eruption angular values should not exceed 56.74°.

Introduction

The term Klinefelter syndrome describes a group of chromosomal disorders in which there is at least one extra X chromosome added to a normal male karyotype, 46, XY. The classic form is the most common chromosomal disorder, in which there is one extra X chromosome resulting in the karyotype of 47, XXY. Klinefelter syndrome is one of the most common sex chromosome disorders affecting approximately one in every 500 men (). Klinefelter syndrome (KS) is an under-diagnosed chromosomal disorder resulting in important challenges for health and medical management. Unfortunately, only 25% of the expected number of patients with KS are diagnosed and only a minority before the puberty onset. Early identification and anticipatory guidance are extremely helpful in managing the patient with KS. Androgen replacement therapy is an important aspect in treating this disorder, which usually starts at puberty, around 12 years of age (, ).

Klinefelter syndrome patients are tall. They have narrow shoulders, broad hips, and gynecomastia. Less distinct phenotypes have also been described (). The KS males are affected by endochondral growth in the cranial base that has a direct influence on jaw growth (). Males with KS have differences in craniofacial shape and morphogenesis (, ), and orofacial morphology (). The difference was found in increased length of hard palate, which is shallow ( - ), larger alveolar arch dimensions () increased tooth size (, ). An increased growth of the final tooth root length in 47, XXY males was also confirmed (, ). So far, different dental anomalies such as taurodontism (, ), multiple impacted teeth (), high prevalence of PDCs () and severe malocclusion have been reported (, ).

A palatally displaced canine manifests itself through positional anomalies and appears to be a product of polygenic, multifactorial inheritance model (). Although the canine develops high near the orbit and sinus, and is buccal to adjacent tooth roots, 85% of impacted canines are located palatally (, ). The palatal- to-buccal impaction ratio ranges from 3:1 to 12:1 (, ).

Traces of genetic influence have focused on bilateral expression of PDC, sex predilection (), familial occurrence (), and on argued evidence of orofacial genetic fields (), on tooth size variation in dentitions with palatal canine displacement (, ), on association with dental and occlusal anomalies (), and on relationship between palatal displacement and the maxillary skeletal width ().

In order to determine whether impaction will occur, different measurement methods using sectors and angular measurement were devised (-). Various radiographic exposures, cone-beam computed tomography and three-dimensional computed tomography can help in evaluating the position of the canines (-). In most cases, panoramic views are reliable to localize impacted teeth in all three planes of space, to view the relationship to the midline and adjacent teeth and to evaluate any resorption (), with the understanding that the source of radiation comes from behind the patient. In this way, the movements are reversed for position.

The aim of this study was to examine the differences of the eruption angle of palatally displaced canines in KS patients and the control group. For this purpose, panorex images were analyzed.

Subjects and methods

This retrospective study examined panorex images of 69 maxillary impacted canines in 38 KS patients aged 20-34 (mean 27 years). The patients were part of a large sample of Croatian individuals with various sex chromosome disorders examined within “Characteristics of the Craniofacial Complex in Gonadal Dysgenesis” research project, which was conducted from 1991 to 1996 in order to investigate dental and craniofacial growth and development of the abovementioned population. A total of 38 men with KS (34 karyotype constitution 47, XXY, one karyotype constitution 48, XXXT, two with mosaic karyotype constitution 47, XXYq), were examined and diagnosed. Their karyotypes had been determined at the Clinic for Gynecology and Obstetrics, University Clinical Centre, Zagreb, Croatia. The karyotype was determined by cytogenetic tests and a chromosome analysis of peripheral lymphocytes and skin fibroblasts. The control group consisted of 78 phenotypically healthy no syndromic males aged 20 -27 (mean 23 years) dental students or patients of the University Clinical Hospital and part of the collection used for the same project from the Department of Dental Anthropology, School of Dental Medicine, University of Zagreb. All individuals had no systemic disease related to bones, and they presented with at least one maxillary impacted canine. Some subjects from the control group had previously undergone orthodontic treatment. The selection criterion for the inclusion in the present study was the presence of maxillary canine. Therefore, one patient with KS was excluded because of earlier extraction of both maxillary canines. Informed consent was obtained from all participants in the study. Ethical approval was obtained from Ethics Committee prior to commencement of the study.

Due to difficulties in locating the original occlusal plane position in 47, XXY males (), the eruption angle of the maxillary canine was measured with the use of a pioneer geometrical method based on construction of Gonion points on panoramic radiographs. Panoramic radiographs were taken by panoramic scanning dental imaging device- Orthopantomograph. A ruler, bow divider, tracing plate, and tracing pencil 0.5 mm lead was used on an acetate tracing foil A4 on a negatoscope. Firstly, the form of the mandible and the maxillary permanent canines were traced out. The Go point was constructed and determined on tracing paper for right and left side and it was connected by a line. The virtual midline of the jaw (S) was determined geometrically, using a bow divider to measure the length of the connection line between the gonions. After measuring the line on the ruler, one half of the distance was used with the bow divider centralized on the Go point of right, subsequently of left side to draw a point above and a point below the Go-Go line. The intersection of these points results in virtual midline of the jaw (S).

The axial line was drawn from the tip of the canine root across the point of the incisal cusp of the canine crown to the reference line between the Go - point and the virtual midline of the jaw for each side. The measured angle was opened distally (Figure 1).

Figure 1

Go – Go points. S: Virtual Medline. A: axial line of canine, the measured angle is opened distally. The right PDC shows a highly increased eruption angle

The means and standard deviations for the two groups were calculated for all values using the Statistical Package for Social Sciences (Mann-Whitney U Test). The differences between the two groups were determined using a Non-parametric Mann Whitney U Test.

Results

69 maxillary canines were found in 37 KS subjects, (five maxillary canines were missing before the examination). Seven KS individuals were found to be affected with PDC; eight canines were displaced in the palatal side. The distribution of unilateral and bilateral subjects in the PDC sample showed that three individuals were affected on the left side, three individuals were affected on the right side, and one patient had PDC on both sides (no significant difference considering the sides). No buccally displaced canines were found in both groups. Statistically, the eruption angle measurements of PDC in the KS patient were marked by a greater variability and distribution (Figure 2). A 95% confidence interval was constructed for mean of each group, the right side of patient group had a wider range of about (60.14°-74.51°) compared with the control group in which it amounted to (55.86°-57.63°), while the left side of the patient group was of (60.64°-72.11°) and the control group was of about (55.96°-57.42°). The minimum value of the eruption angle in KS patients was 44° on the right and 42° on the left side, and the maximum value was 180° on the right side and 162° on the left side. The minimum value of the eruption angle in the control group was 43° on the right side and 44° on the left. The maximum value was 80° on the right side and 76° on the left side (Table 1) (Figure 3).

Figure 2

Comparison of patient and control of right and left sides

Table 1

Description of the samples according to right and left sides of KS patients and controls

SideMeasurement		Rt		Lt
		Patient	Control	Patient	Control
Mean		67.32	56.74	66.38	56.69
95% Confidence Interval for Mean	Lower Bound	60.14	55.86	60.64	55.96
	Upper Bound	74.51	57.63	72.11	57.42
Std. Deviation		21.551	3.939	17.204	3.229
Minimum		44	43	42	44
Maximum		180	80	162	76

Figure 3 Q-Q

plot of right and left sides of patient and control

The mean value of the eruption angle of the maxillary canine in KS was 67.32° on the right side and 66.38° on the left side with no statistical difference (Table 2). In the control group, the eruption angle on the right side was 56.74° and it was 56.69° on the left side with no significant statistical differences between them (Table 3). Although the standard deviation values differ in groups, they were higher in the patient group (21.551) than in the control group (3.939) on the right side. Slightly different results were found on the left side, which means that the KS patient group was not homogeneous regarding the eruption angle on the left side, while values in the control group were alike on both sides. From Table 2 it can be seen that there was a significant difference between those two groups on the right side (P-value <0.01). Table 3 shows a significant difference in results between the two groups, particularly those related to the left side (P-value <0.01).

Table 2

Comparison of KS patients and controls of the right side

SideMeasurement		Rt		Lt
		Patient	Control	Patient	Control
Mean		67.32	56.74	66.38	56.69
95% Confidence Interval for Mean	Lower Bound	60.14	55.86	60.64	55.96
	Upper Bound	74.51	57.63	72.11	57.42
Std. Deviation		21.551	3.939	17.204	3.229
Minimum		44	43	42	44
Maximum		180	80	162	76

Table 3

Comparison of KS patients and controls of the left side

			N		Mean Rank		Sum of Ranks		Mann-Whitney		P-value
Rt	Patient		37		87.20		3226.50		362.500		0.000
	Control		78		44.15		3443.50
	Total		115
				N		Mean Rank		Sum of Ranks		Mann-Whitney		P-value
Lt		Patient		37		89.86		3325.00		264.00		0.000
		Control		78		42.88		3345.00
		Total		115

Discussion

The current study tested the hypothesis that the eruption angle of PDC in KS patients differs from the eruption angle in casual patients. Our results showed increased eruption angle values of PDC in KS patients (by 10.58°) compared with eruption angle values in the casual male control group. Various dentoskeletal features in KS patients have been reported, but, to the authors' knowledge, this is the first study analyzing the eruption angle of PDC in patients with Klinefelter syndrome.

Previous studies (-), have reported characteristic differences of the hard palate size and shape in patients with karyotype 47, XXY chromosome. The results of those studies pointed to significantly increased length of the maxillary base, shallow hard palate, and significantly increased maxillary intermolar width. A large number of studies were focused on casual patients in order to demonstrate a clear association between the PDC of the maxillary canine and anomalous or congenital tooth absence. The results of those studies were different and they pointed to genetic components (, , ) and environmental factors (, ).

In the literature, there are numerous studies with controversial conclusions regarding the available space in dental arches and its contribution to the PDC. Langberg and Peck () investigated into the maxillary dental arch width in subjects with palatally displaced canines. They did not find any significant differences in interpremolar and intermolar widths either in PDC patients or controls. They have provided evidence for refuting previous conclusions which stated that deficiency in maxillary transverse arch width is an associated contributing factor in genesis of the anomaly of palatally displaced canines. Anic-Milosevic et al () investigated into dental and occlusal features associated with PDC in casual age group patients and their contribution to the etiology of PDC. They concluded that there was no statistically significant difference between the groups with regard to maxillary transverse dimensions, maxillary mesiodistal widths, or palatal height for either gender. Thus, considering all these observations, there is no doubt that the extra X chromosome controls and influences the genes responsible for canine size and position as well as it does over the genes responsible for bone growth of the maxilla resulting in palatal displacement of canine / impaction. Furthermore, by relating the effect of genetic factor to general epigenetic factor (sex and growth hormone), control of an extra chromosome over the growth of the craniofacial structures at the time of sexual maturation becomes obvious.

Men with KS have excessive tooth growth. They have taurodontism and radiculomegaly. It has been confirmed that the root elongation of maxillary canine becomes evident between the ages of 8 to 14 (, ), and with regard to the eruption sequence (), and with regard to the remodeling process of the hard palate and maxilla that take place simultaneously. The interrelation between PDC and palatal bone growth shows interference by presence of genes on the extra X chromosome. Suda N and Moriyama K (), have discussed all root abnormalities in a review article and they postulated that root abnormality is seen syndromically but not solely as a dental condition. However, they have not denied the presence of specific molecules that are only expressed during the process of root formations. Also, they have not denied involvement of tooth development regulators. Kanavakis et al. () investigated into the crown-root angulation of lateral incisors adjacent to palatally impacted canines in two groups: one with impacted and one without canine impaction. They found significant differences in crown-to-root angulation between the groups. The root of lateral incisors adjacent to palatally impacted canines was angulated more mesially compared to adjacent lateral incisors in the ‘not impacted’ canine group. Our results confirm this finding if we take into consideration the time of eruption sequence, palatal root inclination and completion of laterals that occur concomitantly with bone formation mechanisms during growth spurt timing.

Radiographs are required to view impacted canines in three dimensions (vertical, mesio-distal and buccopalatal), to view the relationship to the midline and adjacent teeth and to evaluate any resorption (). If an advanced apparatus or software solution cannot be acquired, panoramic radiographs combined with linear and angular measurements are still valuable and accurate. The Go-Go method allows a two dimensional evaluation of PDC and spatial relationships relative to adjacent structures. Localization and measurements of PDC by the Go-Go method on panoramic radiographs contributes to accurate exhibition of inclinations of the PDCs and provides information regarding the adjacent structures. The Go-Go method is a simple, cheap, and constructive method that can be performed in ordinary dental clinics. An increased value of the canine eruption angle may help clinicians in some situations and give guidelines for the assessment of the patient and to estimate the treatment difficulty.

A limitation of this study is associated with the use of panoramic radiographs to determine eruption angle of PDC and missing comparability with other methods on casual patient or with more sophisticated technology. Previous studies have suggested that measurements on panoramic radiographs tend to overestimate the mesiodistal root angulation when compared to a three-dimensional image (). In addition, there is an inherent error in using a two dimensional image to depict three-dimensional structures since the bucco-distal tooth angulations might influence mesio-distal measurements on panoramic radiographs (). Possible age dimorphism in PDC eruption angle could have also affected the results of this investigation. Despite these limitations, there is substantial clinical value to the findings of this study, especially because the panoramic radiograph is still most commonly used radiograph in dentistry. Early detection of disturbed canine eruption in males might alert to the presence of other associated dentoskeletal feature(s). In some instances, the patient should be referred for genetic examinations, determining genotype and karyotype.

In a study by Yu et al (), which was carried out on casual patients, the mesial inclinations angle values of the impacted canines to the occlusal plane were reported to be between 53.8° and 68.5° on average. Significant statistical differences in eruption angle values were observed in KS men. By comparing our findings with the results of other studies performed on casual patients with PDC, the increased mesioangular inclination of PDC seems to have arisen from dental growth genes within the extra X chromosome. The gene(s) influencing dental growth have also control over other events in the process of growth and development. Therefore, the additional X chromosome in KS patients appears to have an influence on the maxillary canine position and its eruption pathway compared with unaffected males.

Conclusions

By using the Go-Go method, dental clinicians can easily and quickly measure and confirm the fact that the eruption angle value exceeds 56.74°. Dental practitioners and orthodontists should be aware of the Klinefelter syndrome when examining males for eruption disturbances of maxillary canines. Early recognition of PDC can lead to early identification and anticipatory guidance that is extremely helpful in treatment of this syndrome. Genetic mechanisms underlying PDC need to be further elucidated with regard to the phenotype of PDC.