ORIGINAL ARTICLE

Three-dimensional longitudinal changes in

craniofacial growth in untreated hemifacial
microsomia patients with cone-beam computed
tomography
Reiko Shibazaki-Yorozuya,a Akira Yamada,b Satoru Nagata,c Kouichi Ueda,d Arthur J. Miller,e and Koutaro Makif
Tokyo, Osaka, and Saitama, Japan, Dallas, Tex, and Irvine and San Francisco, Calif

Introduction: The purpose of this study was to evaluate the concept that the affected and contralateral sides do
not grow at the same rate in patients with hemifacial microsomia. Changes in the cranial base, maxilla, mandible,
and occlusal plane were evaluated on 3-dimensional images from cone-beam computed tomography data in
untreated patients. Methods: Six patients were classified as having mandibular Pruzansky/Kaban type I, IIA,
or IIB hemifacial microsomia. Cone-beam computed tomography (MercuRay; Hitachi, Tokyo, Japan) scans
were taken before orthodontic treatment during both growth and postpuberty periods. Results: The cranial
base as defined by the position of the mastoid process was in a different position between the affected and
contralateral control sides. The nasomaxillary length or height was shorter on the affected side for all 6 patients
with hemifacial microsomia regardless of its severity, and it grew less than on the contralateral control side in 5 of
the 6 patients. The occlusal plane angle became more inclined in 4 of the 6 patients. The mandibular ramus was
shorter on the affected side in all patients and grew less on the affected side in 5 of the 6 patients. The mandibular
body grew slower, the same, or faster than on the control side. Conclusions: The cranial base, position of the
condyle, lengths of the condyle and ramus, and positions of the gonial angle and condyle can vary between the
affected and contralateral control sides of patients with hemifacial microsomia, with the ramus and nasomaxillary
length usually growing slower than they grow on the control side. These results suggest that many factors affect
the growth rate of the craniofacial region and, specifically, the mandible in patients with hemifacial microsomia.
(Am J Orthod Dentofacial Orthop 2014;145:579-94)

H
emifacial microsomia (HFM) refers to a relatively
common craniofacial anomaly that is induced
prenatally in the embryonic or fetal stage and
a
Assistant professor, Department of Orthodontics, School of Dentistry, Showa
University, Tokyo, Japan.
b
Lecturer, Department of Plastic and Reconstructive Surgery, Osaka Medical
School, Osaka, Japan; visiting professor, World Craniofacial Foundation, Dallas,
Tex.
c
Director, Nagata Microtia and Reconstructive Plastic Surgery Clinic, Saitama,
Japan; visiting professor, Department of Plastic and Reconstructive Surgery, Uni-
versity of California Irvine School of Medicine, Irvine, Calif.
d
Professor and chair, Department of Plastic and Reconstructive Surgery, Osaka
Medical School, Osaka, Japan.
e
Professor, Division of Orthodontics, Department of Orofacial Sciences, School of
Dentistry, University of California, San Francisco, Calif.
f
Professor and chair, Department of Orthodontics, School of Dentistry, Showa
University, Tokyo, Japan.
All authors have completed and submitted the ICMJE Form for Disclosure of Po-
tential Conflicts of Interest, and none were reported.
Address correspondence to: Reiko Shibazaki-Yorozuya, Department of Ortho-
dontics, Showa University School of Dentistry, 2-1-1 Kitasenzoku, Ohta-ku,
Tokyo 145-8515, Japan; e-mail, reikosyoroz@dent.showa-u.ac.jp.
Submitted, February 2013; revised and accepted, September 2013.
0889-5406/$36.00
Copyright Ó 2014 by the American Association of Orthodontists.
http://dx.doi.org/10.1016/j.ajodo.2013.09.015
that expresses itself postnatally in the development of
an asymmetrical mandible and associated disorders of
the ipsilateral mandible, maxilla, zygomatic arch, and
auditory bones.1-4 HFM is a progressive skeletal and
soft-tissue deformity.5,6 Although the long-term
concept has been that local embryonic hemorrhage or
disorders in the neuroectodermal migration cause
HFM, it is also possible that interference in chondrogen-
esis induces it.7-10 Animal models have been developed
that appear similar to HFM and involve administering
triazine to pregnant mice to produce hemorrhage in
the stapedial artery8 or exposing animals to retinoic
acid, which kills neural crest cells and interferes with
their movement.9 HFM expresses phenotypically in a
range of disorders from a mild expression involving the
condyle to the most severe condition in which the ramus,
condyle, and coronoid process are missing on 1 side, and
the cranial bones and orbits of the midface can demon-
strate marked asymmetry. HFM is differentiated from
asymmetrical mandibles, which develop only postna-
tally.11 Whereas postnatally developed asymmetrical
579
580 Shibazaki-Yorozuya et al

Table I. Distribution of subjects with HFM

Age Craniofacial deformity scoring systemz

Patient Sex Examination 1 Examination 2 Period* Skeletal typey Affected side MDS CDS CFDS
1 Male 12 y 6 mo 15 y 9 mo 3 y 3 mo I Right 4 3 7
2 Female 12 y 10 mo 16 y 1 mo 3 y 3 mo I Right 4 1 5
3 Male 4 y 10 mo 9 y 2 mo 4 y 3 mo IIA Left 5 9 14
4 Female 6 y 0 mo 8 y 10 mo 2 y 10 mo IIA Left 6 9 15
5 Male 10 y 0 mo 14 y 0 mo 4 y 0 mo IIB Right 13 14 27
6 Male 12 y 1 mo 13 y 8 mo 1 y 7 mo IIB Right 11 13 24
MDS, Mandibular deformity score; CDS, cranial deformity score; CFDS, MDS plus CDS.
*Mean period, 3 y 4 mo; yPruzansky4 and Mulliken and Kaban21 classifications; zHuisinga-Fische et al67

Fig 1. Three-dimensional volumetric surface-rendered views of 2 patients with Pruzansky type I HFM.
The craniofacial skeleton was reconstructed from a 9.6-second scan using the Hitachi Cone Beam CT
MercuRay, generating DICOM formatted data that were reconstituted into surface mesh images with
the CB works software. Four views of each patient (frontal, submental, left and right lateral views)
are shown at 2 time points for patient 1 and patient 2.

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Shibazaki-Yorozuya et al
Fig 2. Three-dimensional volumetric surface-rendered views of 2 patients with Pruzansky type IIA
HFM.
mandibles can result from several causes including
hypoplastic or hyperplastic condylar growth, the expres-
sion of this asymmetrical growth can reflect some char-
acteristics of HFM postnatally.12 Asymmetrical
mandibles can also develop immediately with surgical
intervention, often seen in hemimandibulectomy sub-
jects in whom a portion of the mandible on 1 side, often
with part of the tongue, is removed for surgical treat-
ment of a specific cancer.13
Although HFM is unique in its initial cause, which im-
pairs the normal development of a region of the cranio-
facial skeleton in the embryologic or fetal stage, its
postnatal expression might depend on several additional
factors that contribute to the asymmetry. These factors
include an imbalanced occlusion distributing forces
American Journal of Orthodontics and Dentofacial Orthopedics
581
through the bones differently from a normally symmet-
rical mandible, and jaw muscles such as the temporalis,
masseter, and medial pterygoid contributing more
imbalanced recruitment in the asymmetrical mandible
that might further enhance or extend its abnormal
development.14,15
Approaches to treat HFM vary with different investi-
gators and clinicians and include the concept of early
surgical intervention to correct the abnormal side, ex-
tending the mandible by distraction ontogenesis, or re-
placing the missing condyle with tissue that includes
growth sites or growth center tissues such as a joint
from the ribs.16-19 Other investigators have supported
the second concept of waiting much later and not
intervening in a young subject, hence decreasing the
May 2014  Vol 145  Issue 5
582 Shibazaki-Yorozuya et al

Fig 3. Three-dimensional volumetric surface-rendered views of 2 patients with Pruzansky type IIB
HFM.

episodes of surgical intervention, because the
mandibular asymmetry does not progress.20 Some inves-
tigators advocate modifying the occlusion with a func-
tional appliance and providing support for the
mandibular muscles to function with a more symmetri-
cally positioned mandible in anticipation of completing
surgery on the abnormal side of the mandible.21-23
Three-dimensional (3D) studies of the muscles in HFM
with helical computed tomography (CT) have indicated
that the volumes of the temporalis, masseter, medial,
and lateral pterygoid muscles are significantly smaller
on the affected side.24 Surface electromyographic re-
cordings from the temporalis and masseter muscles in
patients with HFM have shown that subjects with types
I and IIA demonstrate relatively normal recruitment
patterns of clenching, chewing, and biting, but patients
with type IIB demonstrate significant modifications in
recruiting these muscles on the affected side.25,26
Magnetic resonance imaging studies of the
temporomandibular joint indicate that the condyle-
fossa and disc-condyle relationships are fairly normal
on the unaffected side but demonstrate much variation
on the affected side.27 Distraction ontogenesis or osteo-
distraction has proven to be valuable in developing a
stable change in the anteroposterior direction, whereas
vertical lengthening occurs less often.28,29 However,
some investigators suggest that scientific evidence is
still needed from randomized controlled trials on early
distraction ontogenesis in treating patients with
HFM.30 In addition, costrocondral grafts replacing the

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Shibazaki-Yorozuya et al 583

Table II. Classifications of subjects with HFM

Pruzansky4
Grade I Difference in size from the assumed normal side in the same person, characteristics of the ramus are
clearly present.
Grade II Condyle, ramus, and sigmoid notch, while still identifiable, are grossly distorted, and the mandible is
strikingly different in size and shape from any concept of normal.
Grade III Either a grossly distorted ramus with loss of identifiable landmarks or complete agenesis of the ramus.
Kaban et al61
Type I All components are present but hypoplastic to varying degrees. Temporomandibular joint is present but
with reduced cartilage and joint space; hinge movement is normal, but there is reduced translation
during jaw opening.
Type IIA An articulation that allows hinge but not translatory movement is present; there is no morphologically
normal joint. The condylar process is cone shaped and positioned anterior and medial of the normal
position. Coronoid process and gonial angle are well developed.
Type IIB No condylar process that articulates with the temporal bone is present, but there is a coronoid process of
varying size. In some persons, there is a small bony extension at the posterior border of the ramus.
Type III No condylar or coronoid process and no gonial angle area are present.
Harvold et al22
Type I (A) Classic type
Unilateral congenital facial underdevelopment without microphthalmos or ocular dermoids, but with or
without abnormalities of the vertebrae, heart, or renal system. Abnormalities of any type (microtia,
auricular tags or pits, malar hypoplasia, ptosis) on the contralateral side of the face exclude patients
from this category.
Type I (B) Microphthalmic type
Same as type I (A) except for presence of microphthalmos.
Type I (C) Bilateral asymmetrical type
Bilateral congenital facial underdevelopment in which 1 side of the face is more severely involved. Except
for the bilateral requirement, this type can have any other feature of type I A and B
Type I (D) Complex type
Not fitting into any of the above types (I A-C), but no limb deficiency, frontonasal phenotype, or ocular
dermoids.
Type II Limb deficiency type
Unilateral or asymmetrical facial underdevelopment with unilateral or bilateral limb deficiency with or
without ocular abnormalities, including ocular dermoids.
Type III Frontonasal type
Relative unilateral underdevelopment of the face with hypertelorism with or without nares separation,
ocular dermoids, and vertebrae, heart, or renal abnormalities.
Type IV (A, B) Goldenhaar type
Unilateral (type A) or bilateral (type B) facial underdevelopment associated with unilateral or bilateral
ocular dermoids with or without upper lid coloboma.
Huisinga-Fische et al67 (Craniofacial deformity scoring system 5 mandibular deformity score 1 cranial deformity score)
0 1 2 3
Mandibular deformity score (Maximum score, 16)
Gonial notch Not present Present
Mandibular body Normal Minimally hypoplastic Moderately hypoplastic Absent
Condyle Normal Minimally hypoplastic Moderately hypoplastic Absent
Coronoid process Normal Minimally hypoplastic Moderately hypoplastic Absent
Ramus Normal Minimally hypoplastic Moderately hypoplastic Absent
Temporomandibular joint Normal Minimally affected Moderately affected Absent
Cranial deformity score (Maximum score, 19)
Maxillary cleft Not present Present
Foramen magnum Not affected Affected
Maxilla Not affected Affected
Calvarium Not affected Affected
Temporal fossa Not affected Affected
Orbit Normal location and shape Abnormal location or shape Abnormal location and shape
Pterygoid process Normal Dislocation or hypoplastic Partially absent Totally absent
Malar bone Normal Hypoplastic Partially absent Totally absent
Zygomatic arch, maxillary Normal Hypoplastic Partially absent Totally absent
part
Zygomatic arch, temporal Normal Hypoplastic Partially absent Totally absent
part

American Journal of Orthodontics and Dentofacial Orthopedics May 2014  Vol 145  Issue 5
584
Fig 4. Four cranial base measurements from the CBCT-generated 3D volumetric data used to eval-
uate the 6 patients with HFM at 2 time points; a, cranial base width; b, cranial base depth; c, cranial
base angle; d, cranial base height.
Fig 5. Two maxillary measurements from the CBCT-
generated 3D volumetric data used to evaluate the 6 pa-
tients with HFM at 2 time points; a, nasomaxillary length;
b, occlusal plane angle.
ramus and the condyle have had mixed results in pa-
tients with HFM.31
The field of craniofacial biology and medicine has
advanced with several techniques and systems that can
provide new directions in evaluating patients with
HFM and patients who develop asymmetrical mandibles
postnatally. Computerized 3D models have been devel-
oped from lateral and posteroanterior cephalograms us-
ing a vector intercept algorithm.32 Spiral CT analysis has
been used to evaluate patients with HFM 3 dimension-
ally,33-35 but it has long scan times and high levels of
radiation, and is expensive, thus limiting its value in
May 2014  Vol 145  Issue 5 American Journal of Orthodontics and Dentofacial Orthopedics
Shibazaki-Yorozuya et al
longitudinal analysis.15 Cone-beam CT (CBCT) is a major
step forward because it provides multiplanar scans and
surface-rendered 3D volumetric data with much lower
radiation than traditional spiral CT scanners and much
shorter scans (\1 minute), allowing more than 1 time
point in analysis.36-42 Data generated with CBCT can
be inserted into sophisticated finite element models
that are developed from each patient’s unique
craniofacial skeleton, providing a method to assess
how forces are developed on both condyles and in the
bones as the occlusion is altered during treatment in a
patient with HFM.36,37 Computer models are now
available that allow placing the characteristics of the
jaw muscles for each patient into a model that shows
the craniofacial region and that can be modified to
simulate the actual structures of that HFM patient, so
that the forces generated by the jaw muscles can be
predicted, and the stresses and strains that they
generate in the abnormal bony skeleton can be
followed with treatment.43-46 These 3 new tools of
CBCT, CBCT-generated finite element models, and com-
puter real-life simulations of muscle-bone interaction in
the craniofacial region provide powerful approaches to
assess how the surgical intervention to treat the HFM
patient is working. Such analysis is critical to improving
treatment of these patients and any patients developing
true mandibular asymmetries.
Even though HFM can result from early abnormal
development in the embryo or fetus, its resulting
morphologic development over the postnatal period
might be a combination of factors that include abnormal
tissues without the normal potential for growth, and
Shibazaki-Yorozuya et al 585

Fig 6. Eight mandibular measurements from the CBCT-generated 3D volumetric data used to evaluate
the 6 patients with HFM at 2 time points; a, Frankfort horizontal-gonial length; b, Frankfort horizontal-
condyle length; c, corpus length; d, bony midline; e, gonion position width; f, gonion position depth; g,
temporomandibular joint position width; h, temporomandibular joint position depth.

an asymmetrical craniofacial region including the
mandible, which develops forces differently than in a
normal, bilaterally symmetrical system with normal mus-
cles bilaterally. Underdeveloped tissues of the craniofa-
cial region of HFM, as in the condyle, can lack the full
cellular potential of the proliferative and hypertrophic
zones of the cartilage, as well as the translation of carti-
lage into bone.47 In addition, in the extreme cases of
HFM patients with missing ramus and condyle and
much smaller jaw muscles, the muscles on the intact
side provide an asymmetrical set of forces through the
craniofacial skeleton assisted by the malocclusion of
the dentition so that the asymmetrical mandible and
craniofacial skeleton experience strains and stresses
that could maintain or enhance the asymmetry.48
Several longitudinal studies in untreated patients
with HFM have suggested different viewpoints as to
how the asymmetry develops. Some investigators
believe that the facial asymmetry continues to develop
during maturation including puberty.1,6,18,19,21 One
hypothesis to explain this phenomenon is that the
major affected side has little potential for growth even
if it has both structures (ie, condyle, ramus) and grows
slower than the unaffected side. Other investigators
believe that facial asymmetry does not increase with
maturation, and treatment can be delayed until
adolescence, because the growth of the affected side is
similar to that of the contralateral side.20,49-53
Treatment of patients with HFM has often focused
on correcting the mandible and its temporomandibular
joint, with the concept that a more normal mandible
with a bilateral occlusion will not only provide the
more symmetrical face sought by the patient, but also
address the underlying biologic concepts that maintain
these tissues. The practicality of replacing the underde-
veloped bone and muscle tissues in patients with HFM is
continually being pursued. This approach includes os-
teodistraction, implanting transplanted grafts or rib

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586 Shibazaki-Yorozuya et al

Table III. Three-dimensional measurements

Cranial
Cranial base width (R, L)
Cranial base depth (R, L)
Cranial base angle (R, L)
Cranial base height (R, L)
Maxillary
Nasomaxillary length (R, L)
Occlusal plane angle
Mandibular
FH-gonial length (R, L)
FH-condyle length (R, L)
Body length (R, L)
Bony midline
Gonion width (R, L)
Gonion depth (R, L)
TMJ position width (R, L)
TMJ position depth (R, L)
Distance from the lower border of the mastoid process perpendicular to the sagittal plane (nasion-anterior
nasal spine-posterior edge of foramen magnum)
Distance from the lower border of the mastoid process perpendicular to the facial plane (nasion-lower
border point of orbitale [R]-lower border point of orbitale [L])
Angle between the sagittal plane and nasion-lower border of the mastoid process
Distance from the lower border of the mastoid process perpendicular to the Frankfort horizontal plane
(orbitomeatal plane)
Distance from the mesiobuccal cusp of the maxillary first molar perpendicular to the Frankfort horizontal
plane
Angle between the Frankfort horizontal plane and the line between the mesiobuccal cusps of (R, L) of the
maxillary first molars
Distance from the lower border of gonion perpendicular to the Frankfort horizontal plane
Distance from the lateral condylar apex perpendicular to the Frankfort horizontal plane
Distance from the lower border of the symphysis perpendicular to the Frankfort horizontal plane
Distance from the lower border of the symphysis perpendicular to the sagittal plane
Distance from the lower border of gonion perpendicular to the sagittal plane
Distance from the lower border of gonion perpendicular to the facial plane
Distance from the lateral condylar apex perpendicular to the sagittal plane
Distance from the lateral condylar apex perpendicular to the facial plane

R, Right; L, left; FH, Frankfort horizontal; TMJ, temporomandibular joint.

joints with growth potential to replace the condyle,19 or
transplanting muscle with its own nerve and blood sup-
ply to supplement the bony surgery. Exciting new
research approaches include developing condylar
matrices and implanting 3D matrices that induce devel-
opment of a condyle.54,55 The concept of directly
injecting specific chemicals (such as parathyroid
hormone) into the temporomandibular joint has been
tried and suggests potential future ideas of implanting
long-term releases of specific factors that could modify
condylar growth.56
A second animal model also suggests potential
chemical mediators that might be injected and applied
to the condyle. In experimental studies in young, rapidly
growing animals that force them to close to 1 side during
chewing, biting, and gnawing because of an occlusal
splint on the incisors, the animals develop an asymmet-
rical mandible and an altered condylar shape. This ani-
mal model has provided 2 new important facts
comparing how and when the jaw muscles adapt as
the craniofacial skeleton becomes asymmetrical57,58
and detailed analysis of the genetic and cellular
responses in the condyle.59,60 Altering a normally
developing mandible when the jaw closes to 1 side
changes the genetic expression of insulin-like growth
factor-1 and fibroblast growth factor-2 and their recep-
tors, particularly on the side that protrudes during func-
tion. The identification of key chemical markers that
affect condyle growth could be important to new
long-term treatment concepts for controlling the
growth of the underdeveloped condyle in patients
with HFM.
Many previous studies of HFM have focused on po-
tential causes and defining the resulting morphology.
Current classification systems for HFM focus on mandib-
ular hypoplasia. The original classification system of
Pruzansky4 indicated that the mandible has either a
grossly distorted ramus without identifiable landmarks
or complete loss of the condyle and coronoid process
defining grades I, II, and III (Table I).4 Kaban et al61
expanded the classification by subdividing grade II into
type IIA, which has a small condyle and glenoid fossa
anatomically oriented, and type IIB with a nonaligned
condyle and ramus with displacement of the ramus
from the glenoid fossa. Most of these previous morpho-
logic studies were based on 2-dimensional systems, but
CT and CBCT have allowed defining the craniofacial
morphology using 3-dimensionally generated volu-
metric images.62-66 Huisinga-Fische et al67 defined a
craniofacial deformity scoring system that scores both
the craniofacial and the mandibular deformities.68 The
purpose of our study was to evaluate the concept that
the affected and contralateral sides do not grow at the
same rate in patients with HFM.
MATERIAL AND METHODS
This was a longitudinal analysis of patients with
HFM seen in the Department of Orthodontics at the

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Shibazaki-Yorozuya et al
dental hospital of Showa University. Data were gath-
ered by reviewing dental records to find patients
with 2 consecutive CBCT scans and measuring from
CBCT 3D volumetric surface-rendered images. Criteria
for inclusion in this study were unilateral HFM, no
associated craniofacial anomaly, and CBCT scans (CB
MercuRay; Hitachi, Tokyo, Japan) taken before ortho-
dontic treatment, and before or after growth. Six pa-
tients were classified as having mandibular type I,
IIA, or IIB HFM (Table I; Figs 1-3) based on the
schema of Kaban et al61 (Table II).
The measurements, made by 1 investigator (R.S.-Y.),
were obtained from the anatomically accurate 3D volu-
metric images with the analysis software CB works (Hita-
chi).69 Measurements were taken in 3 dimensions and
included 3 sets of data based on the site: cranial base
(Fig 4), maxilla (Fig 5), and mandible (Fig 6, Table III).
The depth, height, and angle of the cranial base were
determined. Each measurements was made 3 times
and compared between the 2 time points, and between
the affected and unaffected sides, using analysis of vari-
ance at a significance level of P \0.05.
Landmarks were determined based on traditional
sites used in normal craniofacial anatomy and often
used in cephalometric 2-dimensional analysis. Some
landmarks were more difficult to define because the
anatomy would significantly alter its form, leading to
the concept that some new landmarks, particularly
appropriate for 3D analysis, need to be developed. The
validity of such measurements can be based on both
the 3D surface-rendered volumetric image and scans
of slices through planes.70,71 Schlicher et al70 showed
that the most inconsistent landmark was the right porion
evaluated in 19 normal patients by 9 orthodontists, and
the most imprecise was the right orbitale, supporting
the concept that alternative landmarks are needed. How-
ever, as Ulrich71 indicated, the right orbitale had wide
variations in his 5 patients: 1 was extremely asymmetric,
but only along the x-axis when the 3 planes were evalu-
ated for each landmark. Similar findings were also shown
by Lagravere et al.72 Studies of landmarks by Brown
et al64 showed that the medio-orbitale and the zygoma-
ticofrontal medial suture point might provide effective
landmarks.
The reliability of the measurements was evaluated by
determining the coefficient of variation for all 18 mea-
surements; this varied from the lowest of 0.24% (cranial
base on the control side) to 5.2% (condylar length on the
control side), with an average of 0.99% (\1%). The co-
efficient of variation was not greater with the measure-
ments on the affected side vs the control side. Although
the measurements were highly consistent when repeated
by 1 investigator, future studies should assess the most
American Journal of Orthodontics and Dentofacial Orthopedics
587
stable landmarks that can be used in 3D evaluations of
the craniofacial region and include the landmarks used
by Ulrich71 (foramen rotundum, zygonion point, glenoid
fossa superior). Ulrich’s analysis using the Bland-Altman
test73 for reproducibility in 3 planes over 3 time points
for 16 measurements showed that each measurement
varied by less than 0.4 mm.
RESULTS
The cranial base width measured from the sagittal
plane to the mastoid process was similar in size between
the 2 sides in the patients with types I and IIA but larger
on the affected side, both laterally and sagittally, in the
patients with type IIB, and it grew slower on the affected
side than on the contralateral control side in these pa-
tients (Fig 4, Table IV). The cranial base depth or the pos-
terior distance of the mastoid from the facial plane was
shorter on the affected side in 1 type I patient and both
type IIA patients, but larger on the affected side of the
type IIB patients. The length of the cranial base depth
did not change in the type IIA and IIB patients on the
affected side, but it increased on the contralateral con-
trol side. The cranial base angle from the sagittal plane
to the mastoid was larger on the affected side in 5 of
the 6 patients with HFM. The cranial base height was
shorter on the affected side in the type IIA and IIB pa-
tients but similar to the contralateral control side in
the type I patients. The cranial base height increased at
a greater rate on the affected side in 5 of the 6 patients
with HFM.
The nasomaxillary length (height) as measured from
the Frankfort horizontal plane to the tip of the maxillary
first molar was always shorter on the affected side than
on the contralateral control side in all 6 patients with
HFM, and also it grew less than the control side in 5 of
the 6 patients (Fig 5, Table V). The occlusal plane
became more inclined over time in 4 patients with
HFM. One type I subject had more growth of nasomax-
illary length (height) on the affected side than on the
contralateral side, and the occlusal plane became flatter
during this time.
The length from the Frankfort horizontal plane to the
gonial angle defined as the length of the ramus was always
smaller on the affected side in all 6 patients (Fig 6, Table
VI). The change in the vertical growth rate of the ramus
was less on the affected side in 5 of the 6 patients with
HFM except for 1 type IIA patient. The condylar length
was longer on the affected side than the contralateral con-
trol side in 5 subjects except for 1 type I subject, and it also
grew at a slower rate on the affected side.
The mandibular body or corpus length grew faster,
slower, or at the same rate, depending on the subject,
May 2014  Vol 145  Issue 5
588 Shibazaki-Yorozuya et al

Table IV. Changes in cranial morphology during the growing period

Cranial base width (mm) Cranial base depth (mm)

Control-
Skeletal Affected Affected Control affected Affected
Patient type* side Age side SD side SD difference side SD
1 I Right 12 y 6 mo 52.96 0.05 52.76 0.25 0.20 67.75 0.09
15 y 9 mo 56.22 0.08 53.02 0.04 3.20 73.38 0.41
Change 3.26 0.26 5.63
% change 106.16% 100.49% 108.31%
2 I Right 12 y 10 mo 48.16 0.16 48.09 0.12 0.07 71.21 0.17
16 y 1 mo 48.80 0.12 48.06 0.01 0.74 77.77 0.37
Change 0.64 0.03 6.56
% change 101.33% 99.94% 109.21%
3 IIA Left 4 y 10 mo 47.63 0.37 48.15 0.25 0.52 67.29 0.30
9 y 2 mo 50.58 0.36 51.49 0.12 0.91 67.29 0.18
Change 2.95 3.34 0.00
% change 106.19% 106.94% 100%
4 IIA Left 6 y 0 mo 46.70 0.69 47.93 0.01 1.23 60.14 0.08
8 y 10 mo 48.11 0.11 49.88 0.54 1.77 60.94 0.37
Change 1.41 1.95 0.80
% change 103.02% 104.07% 101.33%
5 IIB Right 10 y 0 mo 49.68 0.34 36.15 0.34 13.53 58.64 0.03
14 y 0 mo 53.55 0.04 46.44 0.34 7.11 58.84 0.08
Change 3.87 10.29 0.20
% change 107.79% 128.46% 100.34%
6 IIB Right 12 y 1 mo 51.23 0.09 38.94 0.30 12.29 64.11 0.02
13 y 8 mo 53.06 0.49 42.33 0.58 10.73 64.29 0.45
Change 1.83 3.39 0.18
% change 103.57% 108.71% 100.28%

*Pruzansky and Mulliken and Kaban21 classifications.

4

and it showed the least predictable trend. The mandib-
ular body length was slightly shorter on the affected
side in the type I subjects and significantly shorter in
the type IIB subjects. The type IIA subjects had a longer
mandibular body on the affected side compared with
their contralateral control side and demonstrated much
growth, so that the mandibular midline shifted to the
contralateral control side.
The distance of the gonial angle from the sagittal
midline, or the lateral gonial position, was wider on
the affected side in 5 patients with HFM except for 1
type I patient. The posterior length of the gonial angle
from the facial plane was shorter on the affected side
in 4 of the 6 subjects and varied in its rate of growth
compared with the contralateral control side.
The lateral length of the condyle from the sagittal
plane was shorter on the affected side in 5 of the 6 pa-
tients with HFM, occupying a more internal position
during the growth period. It grew at a faster rate on
the affected side in 4 patients. The posterior length of
the condyle from the facial plane was shorter on the
affected side, occupying a more anterior position in 5
patients, and could grow faster or slower than the unaf-
fected side depending on the patient.
DISCUSSION
Modifying the growth of the asymmetrical craniofa-
cial system depends on many factors that can include
concepts related to the absence of growth sites (condyles,
sutures, dentition eruption), the abnormal potential for
cell proliferation and growth of undersized structures,
and the application of forces during function. Modifying
bilateral muscle forces (experimentally impairing the
nerve supply to jaw muscles unilaterally by motor trigem-
inal lesioning) can transform a normal symmetrical
craniofacial skeleton and mandible into an asymmetrical
one, with 1 side of the mandible longer, accompanying
multiple changes in the dentition, maxilla, and temporo-
mandibular joint.48 Assessing growth of an untreated
HFM patient provides some insight as to how these
different factors interact but would be expected to vary
in their individual contributions based on the proportion
of impairment to each factor: absence of structures,
underfunctioning of structures, and asymmetrically

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Shibazaki-Yorozuya et al 589

Table IV. Continued

Cranial base depth (mm) Cranial base angle ( ) Cranial base height (mm)

Control- Control- Control-

affected Affected Control affected Affected Control affected
Control side SD difference side SD side SD difference side SD side SD difference
71.97 0.12 4.22 26.78 0.04 28.31 0.14 1.53 18.00 0.02 21.08 0.02 3.08
73.93 0.10 0.55 26.47 0.02 26.27 0.02 0.20 28.23 0.04 26.94 0.02 1.29
1.96 0.31 2.04 10.23 5.86
102.72% 98.84% 92.79% 156.83% 127.80%
70.53 0.02 0.68 24.61 0.01 23.60 0.10 1.01 27.83 0.11 28.49 0.01 0.66
76.71 0.04 1.06 25.56 0.01 23.77 0.04 1.79 29.31 0.16 28.52 0.01 0.78
6.18 0.95 0.17 1.48 0.03
108.76% 103.86% 100.72% 105.32% 100.11%
72.40 0.11 5.11 27.47 0.07 25.19 0.01 2.28 12.31 0.01 18.48 0.05 6.17
78.80 0.15 11.60 27.64 0.06 25.38 0.04 2.26 18.01 0.06 25.01 0.05 7.00
6.40 0.17 0.19 5.70 6.53
108.84% 100.62% 100.75% 146.30% 135.34%
68.00 0.11 7.86 26.88 0.09 24.05 0.01 2.83 17.18 0.02 29.61 0.03 12.43
72.58 0.01 11.64 27.03 0.08 24.44 0.08 2.59 26.63 0.03 30.43 0.03 3.80
4.58 0.15 0.39 9.45 0.82
106.74% 100.56% 101.62% 155.01% 102.77%
54.82 0.33 3.82 28.49 0.10 23.19 0.03 5.30 17.82 0.03 21.75 0.03 3.93
55.02 0.14 3.82 29.00 0.06 25.03 0.03 3.97 19.98 0.07 22.17 0.40 2.19
0.20 0.51 1.84 2.16 0.42
100.36% 101.79% 107.93% 112.12% 101.93%
60.72 0.03 3.39 27.65 0.13 22.59 0.15 5.06 19.06 0.44 20.77 0.06 1.71
61.08 0.15 3.21 28.46 0.25 22.88 0.35 5.58 21.30 0.28 22.09 0.01 0.79
0.36 0.81 0.29 2.24 1.32
100.59% 102.93% 101.28% 111.75% 106.36%

applied forces across the asymmetrical structures,
including the dentition and joints.
Facial height can be affected by eruption of the
dentition. Occlusal position can be affected by lateral
tooth eruption from deciduous to permanent teeth. In
this study, 2 type IIA subjects and 1 type IIB subject
were in that period of growth when they had the CBCT
scans, and these occlusal position changes were
observed. The other subjects’ deciduous second molar
or permanent first molar was in occlusion at that time
and fully erupted, so that this was not a contributing
factor to their facial growth.
Current HFM classifications describe deformities in
the maxilla, mandible, ear, and nerves. However, most
patients with HFM have cranial bone deformities, which
affect the treatment goals because of their effects on the
facial width and length differences. In this study, the
mastoid process position was more outside of the face
on the affected side than on the contralateral side in
the type IIB patients.
The nasomaxillary length or height was shorter on
the affected side than on the unaffected side in our
sample of different types of subjects with HFM and
also grew at a slower rate in 5 of the 6 subjects. However,
1 type I subject’s nasomaxillary length (height) on the
affected side had more growth than on the contralateral
side, and the occlusal plane became flatter during this
period. These results suggest that type I patients might
not always need functional orthodontic treatment to
correct the asymmetrical occlusal plane.
In patients with HFM, the mandible is always
affected, and mandibular growth is impaired, varying
in degree according to the primary tissue deficiencies.1
In our sample, the ramus was always smaller on the
affected side and grew at a slower rate in 5 of the 6 pa-
tients. Because the main propulsive factor in advancing
the mandible (the condylar growth site) is rudimentary or
missing in type IIB patients, it is understandable that jaw
and facial asymmetries can increase, rather than
improve, with growth. In our study, we found that the
remnant ramus grew less on the affected side in the
type IIB patients.
Interestingly, the condyle on the unaffected side in
the HFM patients appeared to be normal; this raises

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590 Shibazaki-Yorozuya et al

Table V. Changes in maxillary morphology during the growing period

Nasomaxillary length (mm) Occlusal plane angle ( )

Skeletal Affected Affected Control Control-affected Control

Patient type* side Age side SD side SD difference SD side
1 I Right 12 y 6 mo 40.45 0.03 42.10 0.02 1.65 1.38 0.02 Right
15 y 9 mo 38.51 0.02 45.90 0.03 7.39 4.96 0.02 Right
Change 1.94 3.80 3.58
% Change 95.20% 109.03% 359.42%
2 I Right 12 y 10 mo 32.45 0.03 38.51 0.01 6.06 6.79 0.01 Right
16 y 1 mo 37.28 0.01 42.02 0.03 4.74 3.86 0.01 Right
Change 4.83 3.51 2.93
% Change 114.88% 109.11% 56.85%
3 IIA Left 4 y 10 mo 30.81 0.01 31.75 0.01 0.94 3.05 0.01 Left
9 y 2 mo 34.36 0.05 39.71 0.02 5.35 4.68 0.02 Left
Change 3.55 7.96 1.63
% Change 111.52% 125.07% 153.44%
4 IIA Left 6 y 0 mo 31.17 0.04 34.72 0.02 3.55 4.14 0.02 Left
8 y 10 mo 31.45 0.01 36.99 0.02 5.54 7.13 0.01 Left
Change 0.28 2.27 2.99
% Change 100.90% 106.54% 172.22%
5 IIB Right 10 y 0 mo 32.81 0.54 37.62 0.01 4.81 9.01 0.11 Right
14 y 0 mo 33.86 0.05 43.15 0.01 9.29 8.11 0.17 Right
Change 1.05 5.53 0.90
% Change 103.20% 114.70% 90.01%
6 IIB Right 12 y 1 mo 35.48 0.33 41.01 0.01 5.53 6.23 0.01 Right
13 y 8 mo 36.49 0.15 45.27 0.03 8.78 9.22 0.01 Right
Change 1.01 4.26 2.99
% Change 102.85% 110.39% 147.99%

*Pruzansky and Mulliken and Kaban21 classifications.

4

the question as to which side of each patient will func-
tion. Previous analysis by our laboratory on bone miner-
alization in HFM patients with spiral CT data and a
calibrated phantom showed that some patients defi-
nitely demonstrated an asymmetrical distribution of
bone mineralization associated with the skeletal asym-
metry. However, other patients with HFM actually had
a symmetrical pattern between the left and right sides
similar to normal subjects.14 These results might suggest
that patients with HFM vary between 2 types: those who
function with bilateral muscles and forces that use both
sides and distribute forces evenly on both sides, and
those who favor the side that has more cortical bone
with higher bone mineralization.
The question arises as to what happens in patients
with HFM postnatally after the initial damage to the tis-
sues in the embryonic and fetal stages. During postnatal
development, a subject might function on the more
intact, contralateral side with the development of more
effective occlusal and condylar loading forces. Our
data suggest that if the condyle is present on the
affected side as in types I and IIA, despite being smaller
and undersized, it still appears to have the cellular
response to increase the growth of the ramus. Our find-
ings suggest that the initial cellular and tissue insults
that cause the smaller ramus and condyle do not seem
to totally impair the cells in the condyle that can main-
tain its growth site potential. The shorter nasomaxillary
height might also suggest that sutures in the midface
and cranial base have some growth site potentials
despite the initial development of a smaller maxilla, or
that the changes in the maxilla represent responses to
the changing mandible. The difficult issue relates to
the mandibular corpus or body, which appears to modify
its growth rate differently depending on each HFM sub-
ject. Much of its growth depends on bony surface appo-
sition and deposition, which could partially depend on
the posterior dentition. Function can modify the cor-
pus's bony apposition and deposition as well as its shape
that affects its length as seen in the experimental
animals.
The further and continued application of 3D imaging
in longitudinal studies will provide more accurate
anatomic evaluations of how HFM patients develop.
However, treatment will still attempt to restore some
symmetry in both the hard and soft tissues, and

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Shibazaki-Yorozuya et al 591

Table VI. Changes in mandibular morphology during the growing period

FH-gonial length (mm) FH-condyle length (mm) Corpus length (mm)

Control- Control- Control-

Skeletal Affected Affected Control affected Affected Control affected Affected Control affected
Patient type* side Age side SD side SD difference side SD side SD difference side SD side SD difference
1 I Right 12 y 50.16 0.12 54.46 1.38 4.30 4.76 0.01 4.04 0.01 0.72 65.81 4.87 68.49 0.72 2.68
6 mo
15 y 56.91 0.04 66.04 0.40 9.13 6.66 0.32 8.39 0.11 1.73 67.39 1.51 76.43 0.09 9.04
9 mo
Change 6.75 11.58 1.90 4.35 1.58 7.94
% Change 113.50% 121.30% 139.90% 207.70% 102.40% 111.60%
2 I Right 12 y 43.35 0.14 51.94 0.47 8.59 6.68 0.04 3.46 0.31 3.22 68.09 0.30 69.19 0.40 1.10
10 mo
16 y 47.96 0.02 57.84 0.46 9.88 7.93 0.40 7.03 0.05 0.90 73.14 1.53 74.49 0.65 1.35
1 mo
Change 4.61 5.90 1.25 3.57 5.05 5.30
% Change 110.63% 111.36% 118.71% 203.18% 107.42% 107.66%
3 IIA Left 4y 35.48 0.69 43.75 0.34 8.27 6.18 0.16 3.08 0.12 3.10 41.50 0.76 38.72 0.18 2.78
10 mo
9y 42.62 1.00 53.05 0.28 10.43 7.38 0.15 3.66 0.15 3.72 67.83 2.01 64.89 0.04 2.94
2 mo
Change 7.14 9.30 1.20 0.58 26.33 26.17
% Change 120.12% 121.30% 119.42% 118.83% 163.45% 167.59%
4 IIA Left 6y 40.47 0.24 48.07 0.30 7.60 7.52 0.11 1.16 0.23 6.36 57.91 0.28 57.19 0.19 0.72
0 mo
8y 43.28 0.11 49.35 0.10 6.07 2.59 0.03 0.72 0.23 1.87 60.56 0.04 60.07 0.05 0.49
10 mo
Change 2.81 1.28 4.93 0.44 2.65 2.88
% Change 106.94% 102.66% 34.44% 62.07% 104.58% 105.04%
5 IIB Right 10 y 37.88 1.47 44.73 0.26 6.85 15.93 0.24 3.51 0.44 12.41 48.18 0.10 52.34 0.26 4.16
0 mo
14 y 32.73 1.03 47.19 0.03 14.46 12.40 0.10 2.98 0.08 9.42 58.53 0.13 58.88 0.24 0.35
0 mo
Change 5.15 2.46 3.53 0.53 10.35 6.54
% Change 86.40% 105.50% 77.84% 84.90% 121.48% 112.50%
6 IIB Right 12 y 46.22 0.01 55.88 0.57 9.66 13.29 0.35 2.61 0.47 10.68 45.73 0.33 55.27 0.33 9.54
1 mo
13 y 40.67 0.94 59.28 0.46 18.61 9.11 0.56 1.99 0.06 7.12 47.22 0.03 65.06 0.43 17.84
8 mo
Change 5.55 3.40 4.18 0.62 1.49 9.79
% Change 87.99% 106.08% 69.01% 76.25% 103.26% 117.71%

Bony midline (mm) Gonion position width (mm) Gonion position depth (mm)

Skeletal Affected Affected Shifted Affected Control Control-affected Affected Control Control-affected
Patient type* side Age side SD side side SD side SD difference side SD side SD difference
1 I Right 12 y 6 mo 4.94 0.02 Right 48.57 0.05 41.98 0.04 6.59 20.15 0.09 24.92 0.12 4.77
15 y 9 mo 5.09 0.02 Right 49.74 0.07 47.83 0.08 1.91 20.28 0.04 24.41 0.04 4.13
Change 0.15 1.17 5.85 0.13 0.51
% Change 1.03% 102.40% 113.94% 100.65% 97.95%
2 I Right 12 y 10 mo 3.78 0.08 Right 47.24 0.11 39.19 0.69 8.05 35.78 0.20 29.63 0.28 33.15
16 y 1 mo 7.01 0.04 Right 50.38 0.18 40.33 0.07 10.05 37.74 0.19 35.34 0.12 2.40
Change 3.23 3.14 1.14 1.96 5.71
% Change 1.85% 106.65% 102.91% 105.48% 119.27%
3 IIA Left 4 y 10 mo 0.00 0.03 41.50 0.21 38.58 0.31 2.92 29.70 0.09 34.52 0.17 4.82
9 y 2 mo 3.80 0.02 Right 45.18 0.23 43.50 0.05 1.68 29.65 0.21 35.22 0.31 5.57
Change 3.80 3.68 4.92 0.05 0.70
% Change 3.80% 108.87% 112.75% 99.83% 102.03%
4 IIA Left 6 y 0 mo 0.00 0.02 Right 39.52 0.10 36.69 0.20 2.83 24.57 0.09 23.76 0.10 0.81
8 y 10 mo 0.91 0.13 Right 43.46 0.18 39.47 0.05 3.99 25.44 0.18 26.29 0.06 0.85
Change 0.91 3.94 2.78 0.87 2.53
% Change 0.91% 109.97% 107.58% 103.54% 110.65%
5 IIB Right 10 y 0 mo 2.02 0.19 Right 38.97 0.62 33.27 0.34 5.70 22.01 0.10 35.65 0.17 13.64
14 y 0 mo 5.42 0.39 Right 40.74 0.41 34.33 0.36 6.41 29.15 0.32 36.15 0.39 7.00
Change 3.40 1.77 1.06 7.14 0.50
% Change 2.68% 104.54% 103.19% 132.44% 101.40%
6 IIB Right 12 y 1 mo 3.22 0.02 Right 45.18 0.18 39.87 0.03 5.31 28.42 0.12 36.64 0.07 8.22
13 y 8 mo 6.17 0.02 Right 48.92 0.02 40.81 0.08 8.11 30.05 0.34 37.07 0.13 7.02
Change 2.95 3.74 1.02 1.63 0.43
% Change 1.91% 108.28% 102.35% 105.74% 101.17%

American Journal of Orthodontics and Dentofacial Orthopedics May 2014  Vol 145  Issue 5
592 Shibazaki-Yorozuya et al

Table VI. Continued

Temporomandibular joint position width (mm) Temporomandibular joint position depth (mm)

Skeletal Affected Affected Control-affected Affected Control Control-affected

Patient type* side Age side SD Control side SD difference side SD side SD difference
1 I Right 12 y 45.23 0.14 55.75 0.17 10.52 47.27 0.04 54.72 0.14 7.45
6 mo
15 y 54.97 0.01 60.81 0.28 5.84 59.74 0.04 62.76 0.26 3.02
9 mo
Change 9.74 5.06 12.47 8.04
% Change 121.53% 109.08% 126.38% 114.69%
2 I Right 12 y 52.30 0.24 53.86 0.28 1.56 51.28 0.13 48.48 0.03 2.80
10 mo
16 y 56.11 0.16 58.36 0.11 2.25 63.15 0.06 58.95 0.11 4.20
1 mo
Change 3.80 4.50 11.87 10.47
% Change 107.28% 108.35% 123.15% 121.60%
3 IIA Left 4y 40.35 0.17 48.56 0.04 8.21 46.99 0.02 50.31 0.30 3.41
10 mo
9y 45.84 0.09 54.21 0.01 8.37 52.13 0.07 58.70 0.20 6.57
2 mo
Change 5.49 5.65 5.14 8.40
% Change 113.61% 111.64% 110.94% 116.68%
4 IIA Left 6y 48.40 0.21 50.88 0.01 2.48 46.23 0.20 52.97 0.30 6.74
0 mo
8y 51.86 0.39 53.77 0.17 1.91 51.08 0.24 55.36 0.14 4.28
10 mo
Change 3.46 2.89 4.85 2.39
% Change 107.15% 105.68% 110.49% 104.51%
5 IIB Right 10 y 38.04 0.18 45.05 0.06 7.01 36.81 0.04 46.53 0.11 9.72
0 mo
14 y 38.08 0.23 50.14 0.19 12.06 37.16 0.10 49.34 0.49 12.18
0 mo
Change 0.04 5.09 0.35 2.81
% Change 100.11% 111.30% 100.95% 106.04%
6 IIB Right 12 y 42.16 0.22 45.61 0.02 3.45 43.55 0.16 51.32 0.20 7.77
1 mo
13 y 44.51 0.16 46.33 0.03 1.82 45.09 0.32 55.09 0.18 10.00
8 mo
Change 2.35 0.72 1.54 3.77
% Change 105.57% 101.58% 103.54% 107.35%

FH, Frankfort horizontal; FH-gonial length; FH-condyle length; Corpus length.

*Pruzansky4 and Mulliken and Kaban21 classifications.

underlying this concept is the hypothesis that restoring a
more normal symmetrical structure will provide bilateral
function that will support this new structure. Future
studies in how forces are developed during function as
surgeons and orthodontists treat patients with HFM
can provide insight on both presurgical and postsurgical
treatment strategies to enhance the result obtained
morphologically.
CONCLUSIONS
This study of 6 untreated young subjects with varying
degrees of HFM using 3D measurements from anatomi-
cally accurate surface-rendered volumes provides valuable
information on the regions of the craniofacial skeleton
including the cranial base, maxilla, and mandible. This
longitudinal analysis of subjects over 2 to 4 years shows
that the cranial base can vary between the affected and
unaffected sides. The nasomaxillary length is shorter on
the affected side and usually grows less than does the
contralateral control side. The ramus is shorter, and the
ramal growth rate was lower in 5 of the 6 patients. In
contrast, the mandibular body length could be shorter,
longer, or the same for the affected side compared with
the control side. In contrast, the position of the condyle
was usually closer to the midline and the facial plane on
the affected side. These results suggest that many factors
affect the growth rate of the craniofacial region and, spe-
cifically, the mandible in patients with HFM.
ACKNOWLEDGMENTS
We thank Kenneth E. Salyer and the late Edward R.
Genecov of the World Craniofacial Foundation in Dallas,
Tex, for their clinical support and comments.

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Shibazaki-Yorozuya et al
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