Journal of

Anatomy

J. Anat. (2011) 218, pp426438

doi: 10.1111/j.1469-7580.2011.01346.x

Morphological integration between the cranial base

and the face in children and adults
Nikolaos Gkantidis1,2 and Demetrios J. Halazonetis1
1

Department of Orthodontics, School of Dentistry, University of Athens, Athens, Greece

Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Switzerland

Abstract
The primary aim of the present study was to assess morphological covariation between the face and the basicranium (midline and lateral), and to evaluate patterns of integration at two specific developmental stages. A
group of 71 children (610 years) was compared with a group of 71 adults (2035 years). Lateral cephalometric
radiographs were digitized and a total of 28 landmarks were placed on three areas; the midline cranial base,
the lateral cranial base and the face. Geometric morphometric methods were applied and partial least squares
analysis was used to evaluate correlation between the three shape blocks. Morphological integration was tested
both with and without removing the effect of allometry. In children, mainly the midline and, to a lesser extent,
the lateral cranial base were moderately correlated to the face. In adults, the correlation between the face and
the midline cranial base, which ceases development earlier than the lateral base, was reduced. However, the
lateral cranial base retained and even strengthened its correlation to the face. This suggests that the duration
of common developmental timing is an important factor that influences integration between craniofacial structures. However, despite the apparent switch of primary roles between the cranial bases during development,
the patterns of integration remained stable, thereby supporting the role of genetics over function in the establishment and development of craniofacial shape.
Key words: covariation; development; geometric morphometrics; malocclusion.

Introduction
The craniofacial complex serves a multitude of functional
demands in a tightly packed space and is, therefore, a challenging area where the concepts of modularity and integration can improve our understanding of developmental and
evolutionary issues. At the coarsest scale, three main units
can be identified: the cranial base, the cranial vault and the
face. These units, each deriving from embryologically distinct regions and serving separate functional purposes, can
be considered modules. The concept of modularity is difficult to define explicitly (Bolker, 2000). The term module,
as used here, denotes a unit that is internally coherent due
to strong interactions among its parts, but is relatively independent from other such units with which, if connected, it
has weaker or fewer interactions (Klingenberg, 2009).
Strong internal coherency leads to relatively independent

Correspondence
Nikolaos Gkantidis, Department of Orthodontics, School of Dentistry,
University of Athens, 2 Thivon Street, Goudi, Athens, GR-11527,
Greece. T: + 306947262688; F: + 302310999549; E: nikosgant@
yahoo.gr
Accepted for publication 14 January 2011
Article published online 16 February 2011

morphological variation, as has been demonstrated for

functional modules in general, and for the skull modules in
particular (Cheverud, 1996; Lieberman et al. 2000b;
Hallgrmsson et al. 2004; Sardi et al. 2007). In addition to
serving functional demands, the independence of modules
allows morphological evolution through separate, and thus
more flexible, processes (Wagner et al. 2005; Smith, 2006;
Hallgrmsson et al. 2007; Sardi et al. 2007).
However, morphological units cannot be completely isolated from each other as they exist within the coherent
framework of the organism. Anatomical modules are considered integrated when there are mechanisms (embryological, developmental, functional or genetic) that create
interactions between them and thus connect them in morphological and or evolutionary respects (Cheverud, 1996;
Rolian & Willmore, 2009). Such interactions can impose different levels of morphological integration (Moss & Young,
1960; Cheverud, 1982; Enlow, 1990; Hallgrmsson et al.
2007). The term integration, as used in the present study,
refers to the morphological covariation between anatomical parts of individuals within a population. It is the interplay between modularity and integration that determines
the final shape of the organism.
Considering the craniofacial complex, the cranial base
module has been regarded as a major external determinant

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Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 427

of the morphology of the facial module (Enlow, 1990; Lieberman et al. 2000a,b; Goodrich, 2005; Bastir & Rosas, 2006;
Rosas et al. 2008). The cranial base is the center upon which
the rest of the skull grows and attaches, and shows morphological and developmental conservatism in mammals
compared with other regions of the skull (Lieberman et al.
2000a). During growth and development, the neurocranium interacts with the face and vice versa through the basicranium. Thus, the basicranium may have some influence on
the growth and development of the face (Enlow, 1990).
However, recent research, which has mainly focused on
the midline cranial base, has failed to establish a definite
relationship between it (its shape, size and or flexion) and
the morphology of the face, including malocclusion patterns (Lieberman et al. 2000a; Bastir & Rosas, 2006; Polat &
Kaya, 2007; Proff et al. 2008). In an attempt to resolve this
issue, morphometric studies have focused on the role of
the lateral cranial base structures instead (Bastir et al. 2004;
Bastir & Rosas, 2005). These studies have analyzed basicranial and mandibular covariation and suggested that,
because of spatial and temporal relations, the middle cranial fossa (encompassing lateral structures), rather than the
midline cranial base, may be more relevant to the morphological development of the mandible. Also, findings of high
morphological integration between lateral base and facial
structures, compared to almost no integration between
midline base and face in adults (Bastir & Rosas, 2006), and
studies of ontogenetic maturation (Chang et al. 2005)
all indicate that the effective interface between the neurocranium and the face might be the lateral basicranium. A
more recent study of endocranial base variation in modern
humans strengthened the evidence for the dissociation
between midsagittal and lateral components of the basicranium (Bruner & Ripani, 2008).
Developmental and ontogenetic factors that may account
for low correlations between facial patterns and basicranial
angulation (Lieberman et al. 2000a), or low integration
between facial and midline base shape in adults (Bastir &
Rosas, 2006) have not been adequately investigated so far.
However, it is important to explore variations in patterns of
integration during growth and development (Arthur, 2002)
and to know the processes that underlie integration in the
mature organism (Boughner & Hallgrmsson, 2008). This
helps to understand mechanisms that are responsible for
the final shape configuration of the craniofacial complex.
Bastir et al. (2006) investigated the ontogeny of the
human skull in a longitudinal sample using 2D geometric
morphometric methods and concluded that the midline cranial base achieves adult shape at 78 years, while the lateral
cranial floor attains adult shape at 1112 years. The face
achieves adult shape at 1516 years (Bastir et al. 2006), thus
sharing more common developmental timing with the lateral cranial floor compared to that of the midline basicranium. These findings are generally in line with those of
traditional studies that used linear or angular measure-

ments (Buschang et al. 1983; Lieberman & McCarthy, 1999).

In the present study, the term common developmental time
is used to express common ontogenetic periods when
shape changes occur within structures. These biological
procedures occur through coordinated developmental processes, which may finally result in increased morphological
integration.
To test these interpretations, we studied two different
aged human groups using geometric morphometric methods and partial least squares analysis. According to longitudinal ontogenetic data of morphological maturation of the
human skull (Bastir et al. 2006), the younger group (prepubertal children) contained subjects with all three modules
in active growth and development (exhibiting common
developmental timing), whereas in the older group (adults),
the shape of all structures had been completed long ago
(first the middle cranial base, then the lateral base and
finally the face), presumably giving sufficient time for loss
of any transitory morphological integration due to development to occur. Nevertheless, this second group incorporated
a longer period of common developmental timing for the
lateral base and the face. According to the authors knowledge there is no other study evaluating and comparing
patterns of morphological covariation between the face
and the lateral basicranium (anterior, middle and posterior
cranial fossa) with covariation patterns between the face
and the midline cranial base from an ontogenetic and
developmental point of view. The study of Bastir & Rosas
(2006), which first showed the different covariation patterns
between midline base shape and face compared to lateral
basicranium and face, included only adult subjects with
acceptable occlusion that derived from geographically distinct regions. Another unique characteristic of the present
study is that the two groups included subjects of the same
origin, who presented a wide range of dentofacial deformities. The inclusion of subjects with different facial patterns
in the study groups aimed to test for possible interrelationships between cranial base shape and certain malocclusion
patterns (Class I, I, and III), and to assess whether and how
these covariation patterns change through ontogeny. When
we refer to malocclusion we focus on skeletal jaw discrepancies and not on dental relationships.
The primary objective of the present study was to test
the null hypothesis of no difference in strength and
patterns of morphological covariation between the lateral
basicranium and the face compared to that of the midline
basicranium and face, in subjects with various skeletal
malocclusions at two specific developmental stages. By this,
we aimed to investigate whether common developmental
timing is a factor that significantly affects morphological
integration patterns between these structures (increased
morphological integration associated with increase duration of common developmental timing), and to evaluate
the way these patterns change during the development of
the organism.

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428 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

Materials and methods

Sample
The records of the Department of Orthodontics of the Dental
School, University of Athens, were searched to identify orthodontic patients for inclusion in the study. At first, subjects aged
610 and 2035 years before orthodontic treatment were
selected, irrespective of sex and type of malocclusion. Cases with
congenital malformations, systemic diseases or syndromic conditions were excluded. None of the selected patients had previously undergone any kind of orthodontic intervention or had
any kind of pathological disorder. The skeletal maturation stage
of each child was evaluated using the CVM method (Baccetti
et al. 2005) to retain only children before the peak of pubertal
growth (stage CS1 or CS2). The pretreatment lateral cephalometric radiographs of the selected patients that were of good
quality and depicted a reference ruler on the cephalostat for
exact measurement of the magnification factor were used for
the study.
In total, 153 pretreatment radiographs of 82 children and 71
adults fulfilled the inclusion criteria. These subjects presented a
wide range of dental and craniofacial patterns as expected for
an orthodontic population (Proffit et al. 2007). This option was
adopted because, considering the large percentage of malocclusions compared to what is considered ideal occlusion in humans
(Proffit et al. 1998), some scientists consider aspects of malocclusion not to be a true pathological entity, but in many cases a
part of physiologic variation (Mew, 2004). Furthermore, disagreement among epidemiological studies regarding malocclusion reveals the difficulty of establishing a definite limit that
separates normal from abnormal dental or skeletal traits (Proffit
et al. 2007). In the present study, all subjects were considered
healthy, in terms of pathology, according to their medical and
dental history, diagnostic radiographs and photographs. Thus,
any malocclusion was regarded as normal skeletal variation and
not as an abnormal condition or pathological entity.
Reduction of the sample was deemed necessary because, in 2block partial least squares analysis (PLS), the correlation
between PLS scores increases with the number of variables and
decreases with the number of cases (Mitteroecker & Bookstein,
2007). Thus, to obtain valid comparisons, it was necessary to
exclude 11 children to achieve an equal number of subjects in
each group. We opted to retain the younger children, to ensure
that all three modules (midline base, lateral base and face) were
still in active growth and development, or, in the case of the
midline cranial base, when it had just completed its adult shape
configuration (Bastir et al. 2006). Consequently, the younger
group comprised subjects with all modules having common
developmental timing. In contrast, the older group included
subjects with a longer common developmental period for the
lateral base and the face compared to that of the midline base
and the face. Furthermore, the older group was characterized
by the establishment of adult facial morphology and the developmental and functional maturity of all structures of the craniofacial complex. In this group, a considerable amount of time
had passed since all structures had attained their adult shape
(Bastir et al. 2006), presumably giving sufficient time for any
transitory covariation attributed to common developmental
time to fade.
The final material consisted of 142 pretreatment lateral cephalometric radiographs of white patients of Greek ethnic origin,

divided into two age groups: 71 pre-pubertal children (32 males

and 39 females) aged 610 years (mean age 8.5, SD 1.0, range
6.49.8), and 71 adults (23 males and 48 females) aged 20
35 years (mean age 25.4, SD 4.0, range 20.034.5).
The cephalometric radiographs were scanned at 150 dpi, a
resolution considered sufficient for accurate landmark identification (Held et al. 2001), and a set of 30 landmarks was digitized on screen using the VIEWBOX 4 software (dHAL Software,
2009) (Fig. 1). Paired bilateral landmarks were digitized by averaging the left and right sides (Enlow & Hans, 1996). The landmarks represented three craniofacial units, reflecting the threedimensional form of the head; the lateral cranial floor (Latbase:
six landmarks), the midline cranial base (Midbase: five landmarks) and the face (Face: 17 landmarks). The midline cranial
base and the lateral cranial base were represented by similar
number of landmarks because, when studying integration
among several anatomical regions, comparable results can be
obtained only when those regions are captured by the same
number of landmarks (Mitteroecker & Bookstein, 2007). These
cephalometric points (Allpoints: 28 landmarks) were adopted
from Bastir & Rosas (2006) to obtain comparable results. The
two landmarks (Porion and Orbitale) which define the Frankfurt

Fig. 1 Lateral cephalometric radiograph showing the craniofacial

regions and landmarks analyzed in the study. The blue line illustrates
facial structures represented by 17 landmarks: Glabella, Nasion,
Rhinion, ANS, A Point, Supradentale, Posterior maxillary alveolar (most
posterior cementoenamel junction not including 3rd molars), PNS,
Infradentale, B Point, Pogonion, Menton, Inferior mandibular border,
Antegonial notch, Gonion, Ramus flexion, Mandibular Condyle (most
superior point). The green line illustrates midline cranial base
structures represented by five landmarks: Anterior Cribriform,
Posterior Cribriform, Posterior Spenoid plane, Base of Dorsum Sellae,
Basion. The red line illustrates lateral cranial base structures
represented by six landmarks: Anterior orbital roof, Posterior orbital
roof, Spheno-parietal junction (center), Anterior greater sphenoid,
Inferior on MCF, Petroso-parietal junction (center). The black dotted
line illustrates Frankfurt horizontal plane defined by two landmarks:
Porion, Orbitale.

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Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 429

Horizontal plane were not included in the analyses, but were

essential for digitization of Type III landmarks (Bookstein, 1991),
such as Pogonion.

Method error
To test the error of point identification, 20 radiographs were redigitized 10 days after the first digitization by the same investigator (N.G.). Random error was evaluated by assessing: (i) differences between repeated measures of x and y landmark
coordinates using Dahlbergs formula (Houston, 1983), and (ii)
Euclidean distances between the first and second location of
each landmark. The average random error of the x and y point
coordinates was 0.70 mm (range 0.123.74 mm, SD 0.69 mm).
The average value of the landmark distances between repeated
measurements was 1.03 mm (range 0.284.32 mm, SD 0.94 mm).
Systematic error was evaluated by paired t-tests of the x and y
coordinates of each landmark (Houston, 1983). Because of the
large number of t-tests, we performed a Bonferroni correction
of the traditional level of statistical significance (P = 0.05) to
avoid Type I errors. The P-value was adjusted by dividing the initial P-value by the number of t-tests (60) (Zelditch et al. 2004).
No systematic error was detected in any measurement.

Geometric morphometrics and statistical analysis

The four landmark sets (Allpoints, Latbase, Midbase, Face) were
subjected to generalized least squares (GLS) Procrustes superimposition (Rohlf, 1990; Bookstein, 1991; Dryden & Mardia, 1998)
to obtain a set of shape variables. Another set of variables was
obtained from thin-plate splines (TPS) interpolation, which provided the partial warps and uniform component scores for the
sample. Size was determined by using the natural logarithm of
centroid size (lnCS) (Bookstein, 1991; Dryden & Mardia, 1998).

Sexual dimorphism and size differences

Because of the unbalanced male female ratio (approximately
1 : 2) in the adult sample, we tested the presence of sexual
dimorphism within groups. This was performed by permutation
tests using the Procrustes distances between group means as the
test criterion (VIEWBOX 4 software, 10 000 permutations) (Good,
2000).
Furthermore, because allometry is a factor that may influence
morphological integration between structures (Klingenberg,
2009), size differences between groups (children vs. adults) and
within groups (males vs. females) were evaluated by unpaired ttests on lnCS.

Principal components analysis (PCA)

PCA was used to assess the overall variation in the sample and
the distribution of individuals in shape space (Rohlf, 1996) using
VIEWBOX 4 software. Partial Procrustes superimposition was
applied to all 142 subjects, including all 28 landmarks. Principal
components (PC) were supplied as both deformations (coefficients of how the shape coordinates jointly shift) and scores. PC
scores were visualized with plots, and shape differences with
TPS transformation grids.

Allometry regression analysis

Patterns of morphological integration can be influenced by the
presence of allometry (Klingenberg, 2009). Ontogenetic growth

allometry is expected for the child group because it encloses a

long period of active growth (610 years), and static allometry is
expected for the adult group because of the male female ratio
(1 : 2), males being on average larger than females (Rosas &
Bastir, 2002).
Thus, to test for ontogenetic growth allometry in children
and static allometry in adults, we performed multivariate regression of shape variables on size (Monteiro, 1999), independently
for the two groups, using tpsRegr (Rohlf, 2009). The landmark
coordinates were imported into tpsRegr and subjected to GLS
Procrustes superimposition and TPS interpolation, which provided the partial warp and uniform component scores. These
capture the shape variation of the sample and constitute the
dependent variables of multivariate regression, with size (lnCS)
as the independent variable. The multivariate tests of significance for the general linear model are provided by Wilks
Lambda.
Because size differences were found both within and between
groups, and allometry was evident in both developmental
groups (see Results), we decided to remove the effect of size on
shape and obtain a new set of shape variables that were not
influenced by allometry. These new shape variables were
obtained as the residuals of the aforementioned multivariate
regression of shape variables on lnCS and represent shape variation after subtracting allometry. This procedure was performed
six times, separately for each block of shape variables (Face,
Midbase, Latbase; one each for children and adults). Thus, we
were able to explore morphological integration with and without the effect of allometry.

Partial least squares and singular warp analysis

PLS and singular warp analysis were performed to assess patterns of covariation morphological integration between the lateral, the midline cranial base and the face, in the two age
groups. Separate GLS Procrustes superimpositions were performed in each case to examine the individual shape variation
of each structure irrespective of its position within the craniofacial system, and thus other structures. The PLS analysis was performed twice, first including the effect of size on shape and
secondly after removing the effect of allometry on shape variables as described above. In this analysis, the blocks of landmarks are defined a priori. In the present study, 12 blocks of
shape variables (Face, Midbase and Latbase, for children and
adults, with and without allometry) were constructed to make
eight assessments: (i) Face Midbase 610 years, (ii) Face Latbase
610 years, (iii) Face Midbase 2035 years, and (iv) Face Latbase
2035 years, with and without the effect of allometry.
To further test the possibility that the mixed sex effects in our
sample (unbalanced male female ratio in adults) might have
influenced the results, we also repeated the PLS and singular
warp analysis including only female subjects (39 children and 39
adults). We selected this option instead of applying any statistical correction to our original data because we preferred to
retain them in their actual biologic form.
Shape variables were imported into tpsPLS (Rohlf, 2006) for
PLS analysis, which provided pairs of covariance-maximizing linear combinations (singular values) between two blocks of variables. PLS treats the variables of both blocks symmetrically, and
therefore we obtained variables within one block most relevant
for predicting the variables in the other block and vice versa.
These new paired latent variables, or singular warps (SW) (one

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Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

430 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

potentially confounding factor for studying patterns of

morphological integration.

per block) account for as much as possible of the covariation

between the two original sets of variables. The singular warps
display the maximal covariance between both the within-block
shape variables and the shape variables of the other block (Rohlf & Corti, 2000).
The amount of covariance explained by each pair of latent
variables and the cross-set correlations r for paired variables
(singular wrap scores of individuals) determine the biological
significance of each observation covariation detected in each
dimension and the level of integration between blocks. Consequently, these values also determine the dimension(s) that
might be meaningful when interpreting the results (Rohlf &
Corti, 2000). In the present study, we evaluated the first two
dimensions, which represented approximately 80% of the total
covariance. A permutation test (9999 permutations) was used to
assess whether the covariation in the first two dimensions was
statistically significant (Rohlf & Corti, 2000).
Two-block PLS and singular warp analysis were also performed with PLSMAKER6G (Sheets, 2006) to confirm results and
obtain transformation grids. Only the statistically significant
(P < 0.05) or marginally significant (P 0.10) singular warps are
presented.

Principal components analysis

Concerning the configuration of all the landmarks (Allpoints), the first five PCs, accounting for 59.2% of the
total variance, were considered meaningful, based on
inspection of the scree plot. The subjects were graphed
along the PC1 and PC2 axes, which accounted for 37.9%
of the total variance (21.7 and 16.2%, respectively) (Fig. 2).
TPS grids show the wide range of skeletal configurations
included in the sample, in the anteroposterior and vertical
dimensions. Regarding age-related differences, separation
between children and adults was evident along an oblique
direction between PC1 and PC2, but mainly along PC2. It
seems that PC1 mainly describes variation in basicranial
flexion and divergency of skeletal planes, whereas PC2
describes the anteroposterior intermaxillary relationship.
The main characteristic that differentiated children from
adults was a tendency for facial convexity for children
(Fig. 2).

Results
Sexual dimorphism and size differences

Allometry regression analysis

Regarding sexual dimorphism, no statistically significant

separation was found between the sexes in the young
group. The adult group showed sexual dimorphism for the
Allpoints landmark set (P = 0.00), the Face (P = 0.02) and
the Latbase set (P = 0.01). However, sexual dimorphism
and its potential effect on morphological integration were
not directly investigated in the present study because of
inadequate size of the sex subgroups (but see Discussion
for female results). Thus, subjects of both sexes were
pooled in each age group. Although sex is not expected to
influence patterns of integration in adults, this remains to
be tested.
Size (lnCS) differed significantly between children and
adults (P < 0.00) for all landmark sets (Allpoints, Midbase,
Latbase, Face). Within groups, size differences between
males and females were also evident for all landmark sets,
except for Midbase in children (Table 1). Thus, the test for
allometry within groups is justified to control another

Multivariate regression of shape (dependent variables) on

size (lnCS independent variable) demonstrated the significant presence of allometry in both groups and in all landmark configurations examined (Allpoints, Latbase, Face),
except for Midbase in children. In adults, Midbase showed
marginally significant allometry (Table 2). The shape variance that was explained by allometry ranged from 2.2 to
13.0% for Midbase and Latbase in adults, respectively. For
all the remaining landmark configurations that showed significant allometry, the variance explained by the regression
model was approximately 4%, which is considered a rather
small value (Table 2).

PLS and singular warp analysis

Results obtained from 2-block PLS analysis, with and without removing the effect of allometry, are shown in Table 3.

Table 1 Mean of logarithm of centroid size (standard deviation in parentheses) by age group and sex. Unpaired t-tests comparing male and
female subjects within age groups.
lnCS children 610 years
Males
All points
Face
Midbase
Latbase

5.543
5.196
4.238
4.461

(0.037)
(0.040)
(0.033)
(0.051)

lnCS adults 2035 years

Females

P-value

Males

5.516
5.167
4.222
4.436

0.00
0.00
0.07
0.04

5.690
5.347
4.319
4.549

(0.038)
(0.043)
(0.040)
(0.050)

(0.031)
(0.034)
(0.058)
(0.063)

Females

P-value

5.614
5.270
4.274
4.497

0.00
0.00
0.00
0.00

(0.047)
(0.049)
(0.057)
(0.063)

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Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 431

Fig. 2 Scatter plot of the PC scores of the

142 specimens. The x-axis is the first PC axis,
explaining 21.7% of the variance, the y-axis is
the second PC axis, explaining 16.2% of the
variance. Red circles: children, black squares:
adults. The deformed grids illustrate the thinplate spline interpolation of the entire form
showing the transformations implied by
changes along the PC axis 1 and 2 scores
(right and middle top), as well as the
combination of the axes (top left and top
right). The large squares show the position of
each specimen that corresponds to the
deformation showed by each nearby TPS grid.

Table 2 Multivariate regression of shape variables on lnCS,

percentage of the variance explained by the model and P-value
provided by Wilks Lambda.

All points
Face
Midbase
Latbase

Children 610 years

Adults 2035 years

Variance
explained (%)

P-value

Variance
explained (%)

P-value

3.5
4.1
0.7
4.6

0.05
0.01
0.37
0.02

4.5
4.4
2.2
13.0

0.00
0.00
0.05
0.00

The null hypothesis of no difference in morphological integration between the lateral basicranium and the face compared to the midline basicranium and the face at the two
developmental stages (childhood and adult life) was
rejected, supporting the idea that common developmental
timing is an important factor that influences patterns of
integration between craniofacial structures. When only
female subjects were analyzed, the results indicated the
same patterns of integration as those presented for our original mixed sex sample. These data are not presented or
analyzed here due to space considerations.
The presence of allometry influenced the strength of
morphological covariation in specific cases (mainly in
covariation between Latbase and Face, at dimension 2) in
children and adults. However, this did not substantially
affect the patterns of integration and the sequence of
changes through the development and maturation of the
organism (Table 3). Thus, for reasons of clarity, we mention

here only significant (P < 0.05) or marginally significant

(P 0.10) results that were obtained after removing the
effect of allometry (see Materials and methods section).
Regarding statistical significance, one exception is made
for adults, in the case of covariation between Latbase and
Face, at dimension 2, where allometry expressed the most
extensive influence in terms of strength of integration
(r = 0.64, P = 0.00 with allometry, and r = 0.44, P = 0.13
after removing the effects of allometry), reducing covariation below statistical significance. However, because covariation patterns, as evaluated by singular warp analysis, were
similar in both circumstances, the findings are nevertheless
analyzed.
In children, mainly the midline basicranium, but also the
lateral cranial base structures, showed covariation with the
face (Midbase: Dimension 1, r = 0.48, P = 0.10, Latbase:
Dimension 2, r = 0.47, P = 0.02). As midline cranial base
attains adult shape early during ontogeny (Bastir et al.
2006), the morphological integration with the face was
restricted to Dimension 2 (r = 0.46, P = 0.07) in the mature
organism. However, the lateral cranial base structures
strengthened their integration with the face in adulthood
(r = 0.56, P = 0.00 and r = 0.44, P = 0.13, for the first two
dimensions, respectively). These findings indicate that
developmental processes, studied in terms of common
developmental timing, have a significant influence on morphological integration and are in some degree responsible
for the covariation patterns observed in adults. This influence is further explored by singular warp analysis, which is
described below.
Results of the singular warp analysis are presented only
for the statistically significant or marginally significant

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Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

432 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

Table 3 Two-block PLS analysis results based on 9999 permutations.

Age group

Blocks of data

Dimension

Correlation r

P-value

Covariance
explained %

610 years

Midbase Face

1
2
1
2
1
2
1
2

0.49 0.48
0.36 0.38
0.43 0.46
0.41 0.47
0.43 0.40
0.44 0.46
0.56 0.56
0.64 0.44

0.08 0.10
0.52 0.42
0.21 0.15
0.17 0.02
0.17 0.32
0.14 0.07
0.00 0.00
0.00 0.13

44.0 43.5
27.8 26.0
47.7 52.6
29.9 30.5
60.2 50.4
16.6 21.1
61.2 50.5
23.2 31.5

Latbase Face
2035 years

Midbase Face
Latbase Face

First value is without removing allometry and second value is after regressing out allometry. Dimensions represent SW axes,
correlations (r) represent the strength of integration between blocks, P-value shows the statistical significance (permutation test) of
the correlation coefficient (r), and the last column presents the percentage of covariance explained by each dimension. Numbers in
bold signify statistical significance at P 0.10.

correlations, with the exception of covariation between Latbase and Face, at dimension 2 for adults, for reasons
explained earlier. We did not detect appreciable differences
between TPS grids obtained with and without removing
the effect of allometry. It seems that allometry exerts an
influence only on the strength of morphological covariation
between structures, but does not affect the way structures
are morphologically integrated. For consistency, we present
the TPS grids that resulted after regressing out allometry
(Figs 37).
Concerning singular warp analysis, one important finding is that the main characteristics of the morphological
covariation patterns between cranial base structures and
the face remain stable through ontogeny, even though
the strength and amount of integration between structures change.
SW1 explained 43.5% of the covariance of the midline
cranial base with the face in children (Table 3). The correla-

tion observed was moderate (r = 0.48) and close to the

upper limit of marginal significance (P = 0.10). TPS deformation grids showed that a more flexed midline cranial
base and a posteriorly positioned cribriform plate were
associated with a Class III skeletal pattern (i.e. relatively retruded maxilla and protruded mandible) and an increased
lower anterior facial height (Fig. 3).
Concerning covariation patterns between lateral cranial
base shape and facial shape in children, only SW2 was significant (P = 0.02) and revealed a moderate correlation
(r = 0.47), explaining 30.5% of the covariance (Table 3). It
seems that a relatively flat and more anteriorly positioned
middle cranial fossa was associated with a Class II skeletal
pattern (protruded maxilla and slightly retruded mandible
with decreased ramus and corpus flexion) with relatively
increased lower facial height (Fig. 4).
In adults, midline base structures were moderately correlated with the face (r = 0.46, P = 0.07), but only in SW2,

Fig. 3 Plot of singular axis 1 scores for the

face (x-axis) and the midline cranial base
(y-axis) in children that explains 43.5% of
total covariance, after removing allometry.
The associated TPS transformation grids show
the pattern of covariance between these
structures.
2011 The Authors
Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 433

Fig. 4 Plot of singular axis 2 scores for the

face (x-axis) and the lateral cranial base (yaxis) in children, explaining 30.5% of total
covariance, after removing allometry. The
associated TPS transformation grids show the
pattern of covariance between these
structures.

Fig. 5 Plot of singular axis 2 scores for the

face (x-axis) and the midline cranial base (yaxis) in adults, explaining 21.1% of total
covariance, after removing allometry. The
associated TPS transformation grids show the
pattern of covariance between these
structures.

Fig. 6 Plot of singular axis 1 scores for the

face (x-axis) and the lateral cranial base (yaxis) in adults, explaining 50.5% of total
covariance, after removing allometry. The
associated TPS transformation grids show the
pattern of covariance between these
structures.
2011 The Authors
Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

434 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

Fig. 7 Plot of singular axis 2 scores for the

face (x-axis) and the lateral cranial base (yaxis) in adults, explaining 31.5% of total
covariance, after removing allometry. The
associated TPS transformation grids show the
pattern of covariance between these
structures.

which explained 21.1% of the total covariance. As shown

by the transformation grids, a more inclined midline base
with an upward rotated cribriform plate is associated with
a prognathic mandible (Class III pattern), and an increased
lower anterior facial height (Fig. 5). At the anteroposterior
level, this covariation pattern was similar to that observed
for children (Fig. 3).
Correlation between the lateral cranial base shape and
the face was relatively strong, (r = 0.56, P = 0.00) for SW1
in adults, and explained a large amount of the covariance (50.5%) between the two structures. A relatively flat
middle cranial fossa and slightly shortened lateral cranial
base, with the frontal structures more upwardly positioned, was associated with a slight Class II tendency and
a reduced anterior facial height (Fig. 6). SW2 also
revealed a relatively strong (r = 0.64) and statistically significant (P = 0.00) correlation between the lateral cranial
base and the face, but only when allometry was included
in the analysis. The removal of the effect of allometry
weakened the existing correlation (r = 0.44), which also
lost statistical significance (P = 0.13), although it increased
the amount of covariance explained from 23.2 to 31.5%.
This was the greatest influence of allometry on the
strength of morphological integration observed in the
present study. However, the pattern of integration is presented and analyzed here, as it was found unaltered
whether allometry was present or not. A deeper, shorter
and more posteriorly positioned middle cranial fossa was
associated with a retruded maxilla and a protruded mandible (Class III pattern) with increased corpus length, and
decreased lower anterior facial height (Fig. 7). As was the
case for Midbase and Face, the covariation pattern
between the Latbase and Face in adults was similar to
the one observed for children.

Discussion
The present study was conducted on subjects that presented a wide range of dental and skeletal patterns. A matter of concern was whether the sample included subjects
with extreme morphological patterns, resulting perhaps
from undiagnosed pathologies that would skew the results.
We sought these potential outliers by performing PCA analyses on the four landmarks sets, separately for each age
group. After removing those outliers identified by visual
inspection of the PCA plots and equalizing the number of
subjects between groups, we arrived at an alternative study
sample of 65 children and 65 adults. This produced similar
results to those obtained from the original sample (71 children, 71 adults), so it will not be discussed further.
Concerning the variation present in the sample, PCA
clearly demonstrated the wide range of skeletal malocclusion patterns included in the sample, in the anteroposterior
and vertical dimension. The first two PCs described divergency of skeletal planes and anteroposterior intermaxillary
relationship, in accord with previous findings from a different orthodontic sample (Halazonetis, 2004). TPS grids showing variation in overall shape revealed that children, on
average, had a relatively more retruded mandible and protruded maxilla (Class II pattern) than adults (Fig. 2). These
findings are consistent with present knowledge regarding
normal growth and development of the human craniofacial
complex (Bjork & Skieller, 1983; Enlow & Hans, 1996). Individuals with different levels of jaw discrepancies are demonstrated along PC1 axis, but this is expected as the shape
variation of the sample according to skeletal relations is
considerable.
The different male female ratio between the two groups,
the size differences between sexes, and the detected sexual

2011 The Authors

Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 435

dimorphism in the adult sample raise the question of the

presence of ontogenetic or static allometry in the sample.
The influence of allometry on morphological integration
was restricted to the strength of integration (Table 3),
whereas covariation patterns remained unaltered. In general, allometry accounted for only a small percentage of
variation in the present sample (approximately 4%). In the
case of Latbase in adults, where allometry explained 13%
of total variance (Table 2), allometry exerted the greatest
influence on the strength of the detected covariation (SW2
for Face to Latbase).
Considering the possible mixed sex effects on the results,
PLS and singular warp analysis only in females indicated the
same patterns of integration as those presented for the
mixed sex sample. Thus, this potential confounding factor
was excluded. However, a direct comparison of the magnitude of integration is not possible, as sample size considerably affects the strength of morphological covariation
between structures (Mitteroecker & Bookstein, 2007).
As patterns of integration were not significantly influenced by allometry, singular warp analysis is only discussed
without including the effect of size on shape. The findings
in children (Figs 3 and 4) indicate specific roles of each basicranial element in the development of malocclusions (Enlow et al. 1969), already present at least before puberty.
The almost constant relationships between cranial base and
facial structures from childhood to adulthood, despite the
change in primary roles from Midbase to Latbase observed
through ontogeny and developmental maturation, reveal a
potentially strong genetic background that determines the
craniofacial shape configuration from early stages. The
genetic control of certain craniofacial traits was also identified by heritability studies (Sherwood et al. 2008). It is possible that this genetic influence dominates morphogenesis,
setting specific constrains to functional demands that may
only exert secondary influences on that basis. This speculation is further strengthened by the findings of Jeffery &
Spoor (2004) that demonstrated the association of maxillary
protrusion with cranial base retroflexion in the prenatal
period; a pattern also observed in our data for children
(SW1, Fig. 3) and adults (SW2, Fig. 5). The findings concerning the strength of integration in adults are supported by
the study of Bastir & Rosas (2006), who analyzed 2D cephalometric data from 144 adult human skulls using the same
landmark configurations. Their subjects were from geographically distinct regions and were characterized by
acceptable occlusion.
A principal mechanism that results in phylogenetic
changes is the accumulation of variations in growth and
development (Arthur, 2002). Thus, an additional reason for
investigating ontogenetic changes of the craniofacial complex is to explore processes that underlie cranial evolution.
It is known that the angle of the midline cranial base is
established early in ontogeny, but that the face is developing for much longer. As the midline basicranium grows, it

elongates and flexes in the synchondroses (Scott, 1958).

After the eruption of M1, there are no significant increases
in any measure of cranial base flexion in Homo sapiens,
which is consistent with the neural growth trajectory
expansion of the brain (Lieberman & McCarthy, 1999). On
the other hand, the lateral basicranium matures until later
in puberty (Sgouros et al. 1999; Goodrich, 2005) and thus
shares a longer ontogenetic trajectory in common with the
face (Buschang et al. 1983; Bastir et al. 2006). Increases in
basicranial breadth and length also occur in sutures (e.g.
the occipito-mastoid), and the endocranial fossa of the basicranium deepens through drift, in which resorption and
deposition occur along the superior and inferior surfaces,
respectively (Enlow, 1990; Bastir & Rosas, 2009). Data from
the present study suggest that patterns of integration
remain to some degree constant through ontogeny even
though there is a positional change in the primary roles of
covariation patterns from midline base to lateral elements,
which is at least partially explained by the duration of common developmental timing between structures.
From an ontogenetic point of view, the basicranium and
neurocranium grow in tandem in a rapid neural growth
trajectory, forming a highly integrated morphological unit,
the neuro-basicranial complex (Duterloo & Enlow, 1970;
Lieberman et al. 2000a). In contrast, the maxilla and
mandible mostly follow the skeletal growth curve (Buschang et al. 1983). Thus, on one hand, because of spatial
and temporal reasons, the basicranium may set some preconditions on the development of the face. On the other
hand, it is widely supported that facial growth is partially
independent of the neuro-basicranial complex because it
occurs along a skeletal growth trajectory that, to a large
extent, continues after the completion of neural growth
(Moss & Young, 1960; Watts, 1985; Farkas et al. 1992). The
findings of the present study bring into agreement both
viewpoints by presupposing the dissociation of the cranial
base into midline and lateral structures. The midline cranial
base, accompanied by the lateral base to a lesser degree,
seems to be associated with the development of facial
morphology in children, whereas in adults, it is the lateral
cranial base structures that dominate the integration
patterns with the face (Table 3).
Our data indicate that whereas middle cranial base structures are related to facial patterns in children, lateral cranial
base elements assume the primary role later in life, possibly
through developmental and or functional mechanisms
during maturation of the human craniofacial complex.
However, although the specific covariation patterns were
identified and remained relatively stable throughout
ontogeny, the determination of the exact role of the cranial
base structures on the development and establishment of
skeletal jaw discrepancies may require more specific, and
maybe larger, longitudinal samples. Furthermore, the direct
evaluation of the impact of function through a more experimental design would be really informative. However, this is

2011 The Authors

Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

436 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

quite difficult if not impossible for human subjects because

of ethical constraints.
Apart from the common developmental timing hypothesis, the strong integration of the lateral cranial base and the
face in adults may also be attributed to the direct connections between these structures through the masticatory
apparatus. Muscles of mastication grow throughout later
ontogeny under the influence of the growth hormone, and
features affected by this growth might become integrated
through development and function (Marroig & Cheverud,
2001). The role of masticatory muscle function on craniofacial growth and development has been emphasized by several authors (Kiliaridis, 1995, 2006; Raadsheer et al. 1996).
Animal studies demonstrated the influence of masticatory
muscles on bone remodeling and condylar and sutural
growth, whereas human studies have connected the capacity of the masticatory apparatus, and especially of the masseter muscle, with incidences and types of malocclusions at
the vertical, sagittal and transverse planes (Kiliaridis & Kalebo, 1991; Kiliaridis, 1995, 2006; Raadsheer et al. 1996).
An additional reason for the existing differences in
strength and patterns of morphological integration of the
face with midline and lateral aspects of the basicranium
may be the type of growth of the basicranial structures. The
midline basicranium grows mostly via endochondral ossification at synchondroses. In contrast, the lateral basicranium, along with the face and neurocranium, grow via
intramembranous ossification in sutures. Evidence from
recent studies suggests that endochondral ossification may
be less subject to epigenetic interactions (such as relative
brain size) with nearby organs compared with intramembranous ossification. Intramembranous ossification seems to
be influenced by organ growth through mechanical forces
which upregulate transcription factors in sutures to induce
osteogenesis (Opperman, 2000; Wilkie & Morriss-Kay, 2001;
Yu et al. 2001; Spector et al. 2002), but synchondroses elongate much like endochondral growth plates incorporating
some intrinsic growth potential (Cohen et al. 1985; Kreiborg et al. 1993; Jeffery & Spoor, 2002). However, human
and animal studies have suggested that growth of the face
and, mainly, the brain also influences, to some respect,
endochondral growth of the cranial base (Lieberman &
McCarthy, 1999; Hallgrmsson et al. 2007; Lieberman et al.
2008; Bastir et al. 2010; Holton et al. 2010). This supports
the hypothesis that variations in neural and facial growth
patterns express notable influences on the whole craniofacial morphology.
The processes that underlie integration are a key to
understanding the mechanisms of normal or pathological
craniofacial development and evolutionary morphology
(Boughner & Hallgrmsson, 2008). From the present study, it
is evident that lateral cranial base structures consolidate
their role regarding facial morphology in adults through
developmental and maybe functional maturation. On the
other hand, midline cranial base has a primary role in this

field in early developmental stages, possibly setting some

constraints and general directions for further development.
The null hypothesis of no difference in the strength of morphological integration between the face and the lateral
basicranium compared to the face and the midline cranial
base in two developmental stages (childhood and adulthood) was rejected. The face and the lateral basicranium,
which comprise structures with more common developmental timing, presented increased morphological integration
in adults. At present it is not clear whether and to what
degree the processes that produce adult integration are
developmental vs. functional in origin. However, the results
of this study indicate that developmental mechanisms, acting during periods of common developmental timing, are a
key factor in shaping morphological integration.
Future research regarding the role of cranial base structures in facial morphology and malocclusion patterns
should take into account the developmental stage of subjects studied, as well as the dissociation of the cranial base
in middle and lateral structures. Studies of morphological
variation, modularity and patterns of integration between
cranial base structures through ontogeny would also offer
further insights into these issues. Finally, investigation of 3D
data might enhance our knowledge about the developmental mechanisms that lead to the establishment of adult
craniofacial morphology in humans.

Acknowledgements
We are grateful to Markus Bastir for helpful comments on a
first draft of the manuscript. We also thank the Editor and two
anonymous reviewers for their efforts and their valuable comments. This research was supported by the European Virtual
Anthropology Network, a Marie Curie Research Training Network (MRTN-CT-2005-019564).

References
Arthur W (2002) The emerging conceptual framework of
evolutionary developmental biology. Nature 415, 757764.
Baccetti T, Franchi L, McNamara JA Jr (2005) The cervical
vertebral maturation (CVM) method for the assessment of
optimal treatment timing in dentofacial orthopedics. Semin
Orthod 11, 119129.
Bastir M, Rosas A (2005) Hierarchical nature of morphological
integration and modularity in the human posterior face. Am J
Phys Anthropol 128, 2634.
Bastir M, Rosas A (2006) Correlated variation between the
lateral basicranium and the face: a geometric morphometric
study in different human groups. Arch Oral Biol 51, 814
824.
Bastir M, Rosas A (2009) Mosaic evolution of the basicranium in
Homo and its relation to modular development. Evol Biol 36,
5770.
Bastir M, Rosas A, Kuroe K (2004) Petrosal orientation and
mandibular ramus breadth: evidence of a developmental
integrated petroso-mandibular unit. Am J Phys Anthropol 123,
340350.

2011 The Authors

Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

Cranial base and face integration, N. Gkantidis and D. J. Halazonetis 437

Bastir M, Rosas A, OHiggins P (2006) Craniofacial levels and the

morphological maturation of the human skull. J Anat 209,
637654.
Bastir M, Rosas A, Stringer C, et al. (2010) Effects of brain and
face size on basicranial form in human and primate evolution.
J Hum Evol 58, 424431.
Bjork A, Skieller V (1983) Normal and abnormal growth of the
mandible. A synthesis of longitudinal cephalometric implant
studies over a period of 25 years. Eur J Orthod 5, 146.
Bolker JA (2000) Modularity in development and why it matters
in Evo-Devo. Am Zool 40, 770776.
Bookstein FL (1991) Morphometric Tools for Landmark Data.
Geometry and Biology. New York: Cambridge University Press.
Boughner JC, Hallgrmsson B (2008) Biological spacetime and
the temporal integration of functional modules: a case study
of dento-gnathic developmental timing. Dev Dyn 237, 117.
Bruner E, Ripani M (2008) A quantitative and descriptive
approach to morphological variation of the endocranial base
in modern humans. Am J Phys Anthropol 137, 3040.
Buschang PH, Baume RM, Nass GG (1983) A craniofacial growth
maturity gradient for males and females between 4 and
16 years of age. Am J Phys Anthropol 61, 373381.
Chang H, Hsieh S, Tseng Y, et al. (2005) Cranial-base
morphology in children with class III malocclusion. Kaohsiung
J Med Sci 21, 159165.
Cheverud JM (1982) Phenotypic, genetic, and environmental
morphological integration in the cranium. Evolution 36, 499
516.
Cheverud JM (1996) Developmental integration and the
evolution of pleiotropy. Am Zool 36, 4450.
Cohen MM Jr, Walker GF, Phillips C (1985) A morphometric
analysis of the craniofacial configuration in achondroplasia. J
Craniofac Genet Dev Biol 1(Suppl.), 139165.
Dryden IL, Mardia KV (1998) Statistical Shape Analysis. New
York: John Wiley & Sons.
Duterloo HS, Enlow DH (1970) A comparative study of cranial
growth in Homo and Macaca. Am J Anat 127, 357368.
Enlow DH (1990) Facial Growth, 3rd edn. Philadelphia:
Saunders.
Enlow DH, Hans MG (1996) Essentials of Facial Growth.
Philadelphia: W.B. Saunders Company.
Enlow DH, Moyers RE, Hunter WS, et al. (1969) A procedure for
the analysis of intrinsic facial form and growth. Am J Orthod
56, 623.
Farkas LG, Posnick JC, Hreczko TM (1992) Anthropometric
growth study of the head. Cleft Palate Craniofac J 29, 303
318.
Good PI (2000) Permutation Tests: A Practical Guide to
Resampling Methods for Testing Hypotheses. New York:
Springer.
Goodrich JT (2005) Skull base growth in craniosynostosis. Childs
Nerv Syst 21, 871879.
dHAL Software (2009) Viewbox cephalometric software.
Available at http://www.dhal.com.
Halazonetis DJ (2004) Morphometrics for cephalometric
diagnosis. Am J Orthod Dentofacial Orthop 125, 571581.
Hallgrmsson B, Willmore K, Dorval C, et al. (2004) Craniofacial
variability and modularity in macaques and mice. J Exp Zool B
Mol Dev Evol 302, 207225.
Hallgrmsson B, Lieberman DE, Liu W, et al. (2007) Epigenetic
interactions and the structure of phenotypic variation in the
cranium. Evol Dev 9, 7691.

Held CL, Ferguson DJ, Gallo MW (2001) Cephalometric

digitization: a determination of the minimum scanner settings
necessary for precise landmark identification. Am J Orthod
Dentofacial Orthop 119, 472481.
Holton NE, Franciscus RG, Nieves MA, et al. (2010) Sutural
growth restriction and modern human facial evolution: an
experimental study in a pig model. J Anat 216, 4861.
Houston WJ (1983) The analysis of errors in orthodontic
measurements. Am J Orthod 83, 382390.
Jeffery N, Spoor F (2002) Brain size and the human cranial base:
a prenatal perspective. Am J Phys Anthropol 118, 324340.
Jeffery N, Spoor F (2004) Ossification and midline shape
changes of the human fetal cranial base. Am J Phys Anthropol
123, 7890.
Kiliaridis S (1995) Masticatory muscle influence on craniofacial
growth. Acta Odontol Scand 53, 196202.
Kiliaridis S (2006) The importance of masticatory muscle
function in dentofacial growth. Semin Orthod 12, 110119.
Kiliaridis S, Kalebo P (1991) Masseter muscle thickness measured
by ultrasonography and its relation to muscle morphology. J
Dent Res 70, 12621265.
Klingenberg CP (2009) Morphometric integration and
modularity in configurations of landmarks: tools for
evaluating a priori hypotheses. Evol Dev 11, 405421.
Kreiborg S, Marsh JL, Cohen MM Jr, et al. (1993) Comparative
three-dimensional analysis of CT-scans of the calvaria and
cranial base in Apert and Crouzon syndromes. J
Craniomaxillofac Surg 21, 181188.
Lieberman DE, McCarthy RC (1999) The ontogeny of cranial
base angulation in humans and chimpanzees and its
implications for reconstructing pharyngeal dimensions. J Hum
Evol 36, 487517.
Lieberman DE, Pearson OM, Mowbray KM (2000a) Basicranial
influence on overall cranial shape. J Hum Evol 38, 291315.
Lieberman DE, Ross CF, Ravosa MJ (2000b) The primate cranial
base: ontogeny, function, and integration. Am J Phys
Anthropol Suppl 31, 117169.
Lieberman DE, Hallgrmsson B, Liu W, et al. (2008) Spatial
packing, cranial base angulation, and craniofacial shape
variation in the mammalian skull: testing a new model using
mice. J Anat 212, 720735.
Marroig G, Cheverud JM (2001) A comparison of phenotypic
variation and covariation patterns and the role of phylogeny,
ecology, and ontogeny during cranial evolution of new world
monkeys. Evolution 55, 25762600.
Mew JR (2004) The postural basis of malocclusion: a
philosophical overview. Am J Orthod Dentofacial Orthop 126,
729738.
Mitteroecker P, Bookstein F (2007) The conceptual and
statistical relationship between modularity and morphological
integration. Syst Biol 56, 818836.
Monteiro LR (1999) Multivariate regression models and
geometric morphometrics: the search for causal factors in the
analysis of shape. Syst Biol 48, 192199.
Moss ML, Young RW (1960) A functional approach to
craniology. Am J Phys Anthropol 18, 281292.
Opperman LA (2000) Cranial sutures as intramembranous bone
growth sites. Dev Dyn 219, 472485.
Polat OO, Kaya B (2007) Changes in cranial base morphology in
different malocclusions. Orthod Craniofac Res 10, 216221.
Proff P, Will F, Bokan I, et al. (2008) Cranial base features in
skeletal class III patients. Angle Orthod 78, 433439.

2011 The Authors

Journal of Anatomy 2011 Anatomical Society of Great Britain and Ireland

438 Cranial base and face integration, N. Gkantidis and D. J. Halazonetis

Proffit WR, Fields HW Jr, Moray LJ (1998) Prevalence of

malocclusion and orthodontic treatment need in the United
States: estimates from the NHANES III survey. Int J Adult
Orthodon Orthognath Surg 13, 97106.
Proffit WR, Fields HM, Sarver DM (2007) Contemporary
Orthodontics, 4th edn. St. Louis: CV Mosby.
Raadsheer MC, Kiliaridis S, Van Eijden TM, et al. (1996)
Masseter muscle thickness in growing individuals and its
relation to facial morphology. Arch Oral Biol 41, 323332.
Rohlf FJ (1990) Rotational fit (Procrustes) methods. In
Proceedings of the Michigan Morphometrics Workshop (eds
Rohlf FJ, Bookstein FL), pp. 227236, Michigan: University of
Michigan Museum of Zoology.
Rohlf FJ (1996) Morphometric spaces, shape components and
the effects of linear transformations. In Advances in
Morphometrics (ed. Marcus LF), pp. 117128, New York:
Plenum Press.
Rohlf FJ (2006) tpsPLS. Stony Brook, New York: Department of
Ecology and Evolution, State University.
Rohlf FJ (2009) tpsRegr. Stony Brook, New York: Department of
Ecology and Evolution, State University.
Rohlf FJ, Corti M (2000) Use of two-block partial least-squares to
study covariation in shape. Syst Biol 49, 740753.
Rolian C, Willmore KE (2009) Morphological integration at 50:
patterns and processes of integration in biological
anthropology. Evol Dev 36, 14.
Rosas A, Bastir M (2002) Thin-plate spline analysis of allometry
and sexual dimorphism in the human craniofacial complex.
Am J Phys Anthropol 117, 236245.
Rosas A, Bastir M, Alarcon JA, et al. (2008) Thin-plate spline
analysis of the cranial base in African, Asian and European
populations and its relationship with different malocclusions.
Arch Oral Biol 53, 826834.
Sardi ML, Ventrice F, Ramrez Rozzi F (2007) Allometries
throughout the late prenatal and early postnatal human
craniofacial ontogeny. Anat Rec (Hoboken) 290, 11121120.

Scott JH (1958) The cranial base. Am J Phys Anthropol 16, 319

348.
Sgouros S, Natarajan K, Hockley AD, et al. (1999) Skull base
growth in childhood. Pediatr Neurosurg 31, 259268.
Sheets HD (2006) IMP, integrated morphometric package.
Available at http://www.canisius.edu/~sheets/moremorph.html.
Sherwood RJ, Duren DL, Demerath EW, et al. (2008)
Quantitative genetics of modern human cranial variation.
J Hum Evol 54, 909914.
Smith KK (2006) Craniofacial development in marsupial
mammals: developmental origins of evolutionary change. Dev
Dyn 235, 11811193.
Spector JA, Greenwald JA, Warren SM, et al. (2002) Dura mater
biology: autocrine and paracrine effects of fibroblast growth
factor 2. Plast Reconstr Surg 109, 645654.
Wagner GP, Mezey J, Calabretta R (2005) Natural selection and
the origin of modules. In Modularity. Understanding the
Development and Evolution of Natural Complex Systems (eds
Callebaut W, Rasskin-Gutman D), pp. 3349, Cambridge, MA:
Massachusetts Institute of Technology.
Watts ES (1985) Adolescent growth and development of
monkeys, apes and humans. In Nonhuman Primate Models for
Human Growth and Development (ed. Watts ES), pp. 4165,
New York: Alan R. Liss.
Wilkie AO, Morriss-Kay GM (2001) Genetics of craniofacial
development and malformation. Nat Rev Genet 2, 458468.
Yu JC, Lucas JH, Fryberg K, et al. (2001) Extrinsic tension results
in FGF-2 release, membrane permeability change, and
intracellular Ca11 increase in immature cranial sutures.
J Craniofac Surg 12, 391398.
Zelditch ML, Swiderski DL, Sheets HD, et al. (2004) Geometric
Morphometrics for Biologists. A Primer. San Diego: Elsevier
Academic Press.

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