Influence of the cranial base flexion on Class I, II and III malocclusions: a systematic review

ABSTRACT Objective: The aim of this study was to perform a systematic review on the morphological characteristics of the skull base (flexion, anterior length and posterior length) and the concomitant development of malocclusions, by comparing differences in dimorphism, ethnicity and age. Methods: The articles were selected by means of electronic search on BBO, MEDLINE and LILACS databases from 1966 to 2016. A qualitative evaluation of the methodologies used on the articles was also performed. Results: Although the literature on this topic is abundant, only 16 articles were selected for the present systematic review. The cranial base angle itself does not seem to play a significant role in the development of malocclusions. In fact, the cranial base angle is relatively stable at the ages of 5 to 15 years. Conclusions: A more obtuse angle at the skull base, in association or not with a greater anterior length of the cranial base, can contribute to the development of Class II division 1 malocclusions. On the other hand, a more acute angle at the skull base can contribute to a more anterior positioning of the mandible and to the development of Class III malocclusions.


INTRODUCTION
The skull base plays a key role in the craniofacial growth, thus helping to integrate different growth patterns both spatially and functionally, regarding several regions adjacent to the skull -such as brain components, nasal cavity, oral cavity and pharynx. 1 In this way, the skull base supports the brain and allows the neurocranium and viscerocranium to adapt and develop during growth. 2,3 It is reported that the first growth spurt of the skull base occurs between 14 and 32 weeks of intra-uterine life, and the second one occurs during the first year of life. 4 The development of the skull base is closely related to both middle region of the face and mandibular positioning, with its anterior-posterior growth playing an important role in mandibular and nasomaxillary growth, thus directly contributing to the degree of facial prognathism. 5 Based on geometrical relationships, it would be reasonable to say that any change in the skull base flexion might affect the positioning of maxilla and mandible, thus influencing skeletal pattern and occlusion as well. 6 The literature is abundant, but controversial, regarding the influence of the skull base flexion on the development of malocclusions. 6 Although there are studies supporting that the skull base flexion is not a factor in the etiology of malocclusions, others suggest the contrary. 2,7 In fact, several authors 2,[8][9][10][11][12] showed evidence that the skull base has a considerable influence in the inter-maxillary relationships. Ricketts 9 reported that the skull base area has an important influence on total facial prognathism and development of anteroposterior relationship between maxilla and mandible. According to the same author, the Class II malocclusion worsens with age. To Hopkin et al, 10  Among studies showing no influence of the skull base on malocclusions, Hildwein et al 13 found no significant difference in the BaSN angle in individuals with Class II and Class I malocclusions. Kasai et al 14 investigated the relationship between skull base and maxillofacial morphology in Japanese subjects and found no difference between Class I and Class II malocclusions. Similarly, Wilhelm et al 15 observed no difference in the measurements of the skull base regarding Class I and Class II malocclusions. 1 There are many studies corroborating the finding that skull base flexion has an influence on malocclusions, whereas others show no such evidence. Different factors can contribute to these divergent findings, such mixed samples -in terms of age and gender -as well as the use of chronological age instead of skeletal age. Other factors possibly contributing to these divergent findings include the following: lack of radiographic standardization, small sample size, and number of inter-group comparisons. In this way, the influence of the skull base flexion as an etiological factor influencing inter-maxillary relationships is still a matter of debate and investigation. 16 The objective of the present study was to perform a systematic review on the relationship between skull base (flexion, anterior length and posterior length) and the development of malocclusions, by comparing differences in gender dimorphism, ethnicity and age.

Search strategy
The articles selected for this systematic review of the literature were found by means of electronic search on BBO, MEDLINE and LILACS databases, from 1966 to 2016. The keywords used for this bibliographic search were the following: skull base, cephalometry, malocclusion, Class I malocclusion, Class II malocclusion, Class III malocclusion.
Next, a manual search was also performed by analyzing the bibliographic references of the articles according to the systematic review.

Criteria for study selection
The inclusion criteria were the following: » Studies using lateral cephalometric radiography. » Meta-analysis, randomized clinical studies, retrospective and prospective studies. » Studies published from 1966 to 2016.
Influence of the cranial base flexion on Class I, II and III malocclusions: a systematic review original article » Studies addressing non-treated Class I, Class II and Class II malocclusions.
» Studies with subjects aged between 6 and 12 years old (mixed dentition) and those aged between 12 to 18 years old (permanent dentition).
» Studies on skull base using linear (S-N, S-Ar, S-Ba) or angular (NSAr and NsBa) measurements.
» Articles written in Portuguese, English or Spanish idioms.
The exclusion criteria were the following: » Clinical cases, descriptive studies, opinion articles or abstracts.

Article selection
Four researchers have independently examined titles, keywords and abstracts of the articles found in the databases, according to the inclusion and exclusion criteria aforementioned. The articles were consensually selected and integrally considered, and after reading them a final decision was made regarding their inclusion or not in the present study. The articles were classified according to the criteria summarized in Table 1.

RESULTS
A total of 315 articles were initially identified, 8 from BBO, 12 from LILACS and 295 from MED-LINE. After reading the abstracts, only 55 were selected: no article from BBO, 2 from LILACS and 53 from MEDLINE. These were fully considered and after applying the inclusion and exclusion criteria, 39 articles were excluded and 16 remained, all from the MEDLINE database (Table 2). Next, another article was excluded due to lack of the measurements considered for review.
A qualitative evaluation of the methodology used by these articles was performed according to previous studies. 17,18 The variables being considered for review are listed in Table 1, including corresponding values. Table 2 shows the articles presenting more accurate methodologies. Each article was given points according to the items evaluated, as can be seen in Table 1. Each item had a maximum score of 2 points if there was a consensus on it, otherwise 1 point was given. This procedure was applied to each article. Therefore, each article could reach a maximum score of 20 points, thus allowing the study quality to be ranked as follows: ≤ 10 points = low score; > 10 and ≤15 = average score; > 15 and ≤ 18 = moderately high score; and > 18 points = high score. Table 3 shows the sample characteristics, including the objective of each article, and Table 4 lists the epitomes. In this last table, a study 22 was excluded because it did not present total measures, but rather growth increments.

Age
Seven studies have investigated the growth of the skull base by comparing the data obtained from dif-ferent age groups 16,20,22,23,24,28,37 with three 22,24,28 of them using samples of individuals with Class III malocclusion and whose age ranged from 5 to 18 years old. These individuals were found 22 to have a yearly increment in the length of the anterior skull base in all age groups (6 to 18 years old), which was smaller than 1 mm for women and approximately equal to 1 mm for men, similar to the growth estimated for individuals with Class I malocclusion. In another study 24 comparing Class III malocclusion to Class I malocclusion in individuals aged 5 to 11 years old, it was found that NSBa angle was more acute in the latter at ages of 5, 8, and 9 years old, and that NSAr angle had the same trend; but no statistically significant difference was found at 8 years old. Researchers 23 have reported that the skull base of Japanese individuals with Class II division 1 malocclusion had a significantly smaller anterior length at 10 years and 10 months to 15 years and 10 months old compared to other age groups,    involving individuals with same malocclusion and race (Group 1: 7 years and 6 months to 13 years and 6 months old; and Group 2: 9 years and 1 month to 13 years and 6 months old). On the other hand, another study 29 compared individuals with Class II division 1 malocclusion to controls and found that the length of the anterior skull base was statistically greater in all six age groups studied (females aged 10, 12, 14 years old, and males aged 10, 12, 14 years old). Two studies 20,28 had samples with different age groups, but it was not possible to use all data because the first study 20 had compared age groups of 1 month, 2 years and 14 years old, whereas the second study 28 had assessed neither flexion nor the skull base length at different age groups. For Yoon and Chung, 37 which compared Class I with Class II at three different ages (9, 14 and 18 years -all female), no difference was observed in the flexion or length of the anterior skull base.

Ethnic group
Three studies have assessed different ethnic groups, 26,28,29 with Asian being compared to Caucasian individuals in most cases, and significant differences being found. The length of the anterior skull base was found to be greater for Japanese than for Caucasian females. 26 However, a study 28 reported a greater anterior skull base as well as a more acute NSAr angle in European/American than in Korean individuals. Similarly, with regard to the length of the anterior skull base, a study 29 showed this measurement was smaller in Chinese than in Swedish individuals for both types of malocclusions (Class I and Class II), with the posterior length (S-Ba) being also smaller in Chinese individuals with Class II malocclusion. Another study 24 evaluated two ethnic groups but no comparison was possible because of the lack of data on skull base structures regarding Caucasian individuals.

Dimorphism
Six studies have evaluated the relationship between sexual dimorphism and development of the skull base, 22,25,27,30,16,29 but no significant difference was found in the angular measurements. However, one study 25 showed that linear measurements (S-N, S-Ar and S-Ba) were significantly greater in Icelander male children compared to female ones with Class I and Class II malocclusions.

Malocclusion differences
Of the 16 articles selected, only one has not compared flexion or length of the skull base to some type of malocclusion. 22 Two studies 1,19 compared flexion or length of the skull base in individuals with Class I, Class II and Class III malocclusions. One of these studies 19 found greater angular measurements for the skull base in Class II division 1 malocclusion, compared to Class I malocclusion. In this same study, no difference was found between Class I malocclusion and other ones, regarding such angular measurements, whereas the length of the anterior and posterior skull base were greater in the cases of Class II malocclusion. However, the other study 1 reported significant differences in the skull base length between the three types of malocclusion. Studies 21,24,31 have also compared Class III malocclusion to normal occlusion, whereas another one 28 compared this condition between Caucasian and Korean individuals. All these studies found similar results, with the length of the anterior skull base being smaller in Korean individuals with Class III malocclusion and skull base flexion tending to be more acute in Caucasian individuals with the same condition.
Among these seven studies 16,20,23,25,27,30,37 comparing Class II malocclusion to Class I malocclusion, similar results have been reported. For example, individuals with Class II malocclusion had greater anterior and posterior lengths and more obtuse angular measurements regarding the skull base. However, one study 23 reported a smaller length of the skull base in Japanese girls with Class I malocclusion presenting permanent dentition, whereas another 30 found no significant differences in the skull base flexion compared to normal occlusion. In the study, the compared groups (Class I and Class II) showed no differences in the length of the anterior skull base and flexion of the cranial base.

DISCUSSION
The skull base not only supports and protects the brain but also articulates the cranium with vertebral column, maxilla and mandible. One of its key functions has to do with adaptation and protection, including a shock-absorbing area between brain, face and pharyngeal region, whose growths occur differently. The growth of the skull base occurs by means of a complex balance between sutural growth, prolongation of synchondroses, extensive cortical sliding, and remodelling. This combination allows an increase in the differential growth between base and vault of the skull, expansion of the contours of the various endo-cranial fossae, maintenance of vessel and nerve pathways, and prolongation of the processes, such as hypophysis. Prolongation of the skull base occurs with the growth of synchondroses and direct cortical growth. The cortical sliding of the skull floor produces several degrees of growth movement at different regions, usually towards the ecto-cranial direction, with apposition proportional to the external surface. 5 Enlow 32 has shown that maxilla growth is influenced by the skull base, which in turn, is influenced by the growth of the brain. The mandible, because of its distant positioning, acts more independently, despite being articulated with glenoid fossa, thus being a potential factor influencing the skull base.
To better understand the cephalometric aspects, the skull base is divided into anterior and posterior lengths, the former extending anteriorly from sella turcica (S) to nasofrontal suture (N), and the latter extending from sella turcica to the anterior edge of the foramen magnum, defined as Ba. 21 There is a consensus that the length of the anterior skull base corresponds to the linear N-S distance, but the same cannot be said about the posterior region, which corresponds to either S-Ba or S-Ar linear distances. 19 Björk 2 supported the use of the latter, as it is more easily visualized, with most studies using this measurement. Verjanne and Koski 33 suggested the use of Ba to measure the skull base angle as they considered the S-Ar measurement too distant; Kerr and Adams 34 used Ba to measure the skull base angle. Bhatia and Leighton 35 used N-S-Ba, N-S-Art as well as S-Ba and S-Art, and found similar measurements.
According to the other authors, 19 the skull base follows a neural (anterior region) and somatic (posterior region) growth pattern despite its cartilaginous origin (chondrocranium). After birth, especially in the early childhood, the growth of the anterior portion occurs mainly due to the increase in frontal sinus and remodelling of the nasal region, whereas the growth of the posterior region is related to the interstitial growth occurring in the spheno-occipital synchondrosis.