Objective: To examine the oropharynx of patients with ectodermal dysplasia showing maxillary retrusion and mandibular protrusion with a short and concave facial structure using cone-beam computed tomography method. Ectodermal dysplasia refers to the congenital disorder defined by the abnormal development of the structure originating from the ectoderm. Study Design: In order to examine the oropharynx airway, measurements and statistical evaluations were made in 3 levels in sagittal and transversal directions on three-dimensional cone beam computed tomography images obtained from 14 individuals divided into 2 groups as Ectodermal Dysplasia group (n=7) and Control group (n=7). Results: As a result of statistical analysis, no statistically significant difference was found between the groups at any level or direction in metric measurements performed on all 3 planes taken at the sagittal and transversal levels (p>0.05). Conclusion: Our findings on ectodermal dysplasia are similar to Class III malpositions that show similarity with ectodermal dysplasia.

1. 129
OBJECTIVE: To examine the oropharynx of patients
with ectodermal dysplasia showing maxillary retrusion
and mandibular protrusion with a short and concave
facial structure using cone-beam computed tomography
method. Ectodermal dysplasia refers to the congenital
disorder defined by the abnormal development of the
structure originating from the ectoderm.
STUDY DESIGN: In order to examine the oropharynx
airway, measurements and statistical evaluations were
made in 3 levels in sagittal and transversal directions
on three-dimensional cone beam computed tomography
images obtained from 14 individuals divided into 2
groups as Ectodermal Dysplasia group (n=7) and Con­
trol group (n=7).
RESULTS: As a result of statistical analysis, no sta-
tistically significant difference was found between the
groups at any level or direction in metric measurements
performed on all 3 planes taken at the sagittal and trans-
versal levels (p>0.05).
CONCLUSION: Our findings on ectodermal dysplasia
are similar to Class III malpositions that show similarity
with ectodermal dysplasia. (Anal Quant Cytopathol
Histpathol 2021;43:129–136)
Keywords: 3D CBCT; airway obstruction; cephalo-
metry; cone-beam computed tomography; conical
beam computed tomography; ectodermal dyspla-
sia; imaging, three-dimensional; mandible; maxil-
la; mouth breathing; nasal cavity; nasopharynx;
oropharynx; pharyngeal airway morphology; skull,
diagnostic imaging.
Ectodermal dysplasia describes a large and com­
plex group of congenital disorders characterized by
the abnormal development of two or more struc-
tures derived from the embryonic ectodermal lay­
er.1 The most common type of ectodermal dyspla-
sia is hypohydrotic ectodermal dysplasia (HED),2
also referred to as Christ-Siemens-Touraine syn­
drome or anhidrotic dysplasia in the literature.3
It was defined in 1792,4 its incidence is 1:100,000,3
and more than 200 different pathological condi-
tions have been clinically reported and identified as
ectodermal dysplasia.
Ectoderm is the outermost layer of the three
layers that develop in the embryo and form the
central nervous system, peripheral nervous sys-
tem, sweat glands, hair, nails, and tooth enamel.4
Abnormal development in the ectoderm layer
directly affects these tissues and the organs con­
sisting of these tissues. It is possible to list the
clinical symptoms of individuals with ectodermal
Analytical and Quantitative Cytopathology and Histopathology®
0884-6812/21/4303-0129/$18.00/0 © Science Printers and Publishers, Inc.
Analytical and Quantitative Cytopathology and Histopathology®
Three-Dimensional Investigation of the Effects
of Ectodermal Dysplasia on the Oropharynx
An Anatomical Study
Beyza Karadede Ünal, D.D.S., Ph.D.
From the Department of Orthodontics, Faculty of Dentistry, I
∙
zmir Katip Çelebi University, I
∙
zmir, Turkey.
Beyza Karadede Ünal is Assistant Professor (ORCID: 0000-0002-0035-0444).
Presented as a poster (“Investigation of Oropharyngeal Airways of Individuals with Ectodermal Dysplasia with Three-Dimensional
Computed Tomography Method”) at the 12th International Congress of the Turkish Orthodontics Association, Ankara, Turkey, October
24–28, 2010.
Address correspondence to: Beyza Karadede Ünal, D.D.S., Ph.D., I
∙
zmir Katip Çelebi Üniversitesi DişHekimliği Fakültesi, Aydınlıkevler
Mahallesi, Cemil Meriç Bulvarı, 6780 Sokak. No. 48, Çiğli, I
∙
zmir 35640, Türkiye (dtbeyzaunalkaradede@gmail.com).
Financial Disclosure: The author has no connection to any companies or products mentioned in this article.

2. dysplasia as follows: hypotrichosis (insufficient
hair growth), hypohydrosis (insufficient sweat
secretion), and cranial anomalies. This triple thin
hair is characterized by shape and number ab­
normalities in the teeth and insufficient sweat
secretion.3 Although affected people do not have
sweat glands, they may generally be thin-haired
or hairless.5
Symptoms are less common in women, while
HED is more common in men.6 Additionally, an-
hidrotic ectodermal dysplasia is autosomal reces-
sive and is characterized by the absence of sweat
and sebaceous glands. The same findings are seen
in hypohydrotic type in a milder form. In hydrotic
type, which is autosomal dominant, sweat and
sebaceous glands function normally.3 Ectodermal
dysplasia patients can be affected by the following
oral symptoms: anodontics, hippodontics, conical
teeth, and lack of development in the alveolar
bone.2 They often have a disproportionately small
face due to an anomaly in craniofacial develop-
ment; their frontal bones are prominent and their
nasal structures are flattened. Individuals with
ectodermal dysplasia who have facial concavity
and mid-face insufficiency have maxillary retru-
sion and, consequently, mandibular protrusion.
In these individuals there is an insufficiency in
the vertical dimension and a predisposition to
Class III malocclusion.7 These features give chil-
dren the appearance of a distinctly aged and tooth­
less face. Dentists should take a comprehensive
and multidisciplinary approach to these patients
and develop and regulate their dental structures,
mastication functions, growth directions, and or-
thognathic conditions.3
It is argued that there is a significant relation-
ship between airway and facial morphology.8 The
pharynx is a conductive structure located in the
midline of the neck. It is the main structure, in
addition to the oral cavity, shared by two organ
systems, i.e., the gastrointestinal tract and the
respiratory system. It is funnel-shaped, with its
upper end being wider and located just below the
lower surface of the skull and its lower end being
narrower and located at the level of the sixth
cervical vertebra where the commencement of the
esophagus posteriorly and the larynx anteriorly
takes place. Its muscular-membranous integrity
allows it to mediate several vital functions related
to either organ systems, e.g., food swallowing, air
conduction, and voice production. Regionally, the
pharynx divides into three parts which are from
superior to inferior: (1) the nasal pharynx, located
behind the posterior nasal apertures (choanae),
(2) the oral pharynx, located behind the opening
of the oral cavity, and (3) the laryngeal pharynx,
located behind the inlet (opening) of the larynx.
First, the nasal pharynx is only related to the
respiratory tract as air passes through it from the
nasal cavities. Second, the oral pharynx is a con­
tinuation of the oral cavity and functions to pass
the bolus toward the laryngeal pharynx below.9
The nasopharynx shows morphological differ­
ences in relation to the craniofacial development
of individuals. The location of the atlas, which is
located in front of the basion, is important when
determining the distance of the pharyngeal airway
in the anteroposterior direction. Considering the
position of the atlas and the posterior nasal spine,
it has been reported that there is no increase in the
anteropos­
terior distance of the pharyngeal space,
and the atlas position takes a fixed position in the
1st and 2nd years.10
Ceylan and Oktay examined the pharyngeal
dimensions in lateral cephalometric radiographs
of 90 people. They concluded that individuals with
angle between points A and B (point A: deepest
point on midsagittal plane between anterior nasal
spine and prosthion; point B: the deepest midline
point on the mandible between infradentale and
pogonion) (ANB) <1° had a greater oropharynx
area than did individuals with ANB >5°. In addi-
tion, statistically significant findings were report-
ed between pharyngeal dimensions and craniofa-
cial anomalies.11 Iwasaki et al12 reported that Class
III patients had hypertrophic palatinal tonsils, their
tongue was located lower, and their oropharyn-
geal airway was flatter and wider than that in
Class I individuals. They also reported that this
condition also causes changes in the occlusal re-
lationship and upper airway. Martin et al13 found
that lower pharyngeal size increased in class III
patients.
In a study in which the size and shape of
the pharynx in patients with different craniofacial
morphological structures were examined by coni-
cal beam computed tomography (CBCT) in three
directions of space, it was concluded that while
there were differences between anteroposterior
airway measurements by level, the magnitude of
that difference was due to the skeletal morphology
of the individual. In the same study, while there
was no difference in transversal airway measure­
ments according to the skeletal pattern of the
130 Analytical and Quantitative Cytopathology and Histopathology®
Ünal

3. individuals, the measurements at the inferior level
in the transversal direction were observed to be
significantly higher than the superior level in all
cases.14
In a study investigating the relationship be-
tween upper airways and craniofacial morphology
with CBCT, sagittal, transversal dimensions, and
total and partial volumes of the pharyngeal air-
way were correlated with cephalometric mea­
surements. There was no significant relationship
found. It was concluded that the differences in
craniofacial morphology determined by the sagit-
tal relationship were not related to the variations
in the upper airway volumes.15 Three-dimensional
structures have been examined with lateral cepha-
lometric devices until today; although this meth-
od has been widely used, the accuracy of the
two-dimensional projection of a three-dimensional
anatomical structure is doubtful. In a study con-
ducted for this purpose, the correlation of sagittal
and transversal linear measurements, in cross-
sectional area and volume measurements of the
upper airway, was examined with CBCT, and
it was concluded that linear measurements per-
formed by cephalometric analysis of the upper
airway cannot be made accurately.16
In 1973 Linder-Aronson and Henrikson,17 in a
study in which they calculated the anteroposte-
rior size of the nasopharynx airway on lateral ra-
diographs in children aged 6–12 years with mouth
and nose breathing, concluded that the variables
showed the same differences and were equal-
ly usable. However, Rodenstein et al18 examined
the shape and dimensions of the oropharynx in
healthy individuals, snorers, and patients with ob-
structive sleep apnea using magnetic resonance
imaging and found no significant difference be-
tween the groups. Additionally, it has been stated
that the relationship between craniofacial morpho-
logy and airway volume is interrelated and may
narrow the airway volume in sagittal deficiency
in the maxilla or mandible.19 Correlation between
narrow airway volume and obstructive sleep ap-
nea has been reported. In a similar study it was
shown that individuals with obstructive sleep
apnea had significantly smaller minimum cross-
sectional areas (<100 mm2) as compared to the
control group (>100 mm2).20 As shown by many
studies to date, patients with craniofacial ano-
malies are at a much higher risk of developing
obstructive sleep apnea than are controls.21 Ac-
cording to this information, individuals with ecto-
dermal dysplasia have a predisposition to obstruc-
tive sleep apnea due to skeletal abnormalities and
absence or inability of the mucous glands, as well
as many high risks such as sinusitis, rhinitis, upper
respiratory tract infections, and difficulty breathing
through the nose.7
For these reasons, it is particularly important to
investigate airway volume and anatomical features
in patients with ectodermal dysplasia. There are
very few studies on the oropharyngeal airway in
ectodermal dysplasia patients. Most of these stud-
ies have been done on lateral cephalometric ra-
diographs. Cone beam computed tomography
(CBCT) is very popular in recent years because it
can provide detailed three-dimensional images. In
this study it was aimed to examine anatomically
the oropharynx of ectodermal dysplasia patients
with short and concave facial structure, maxillary
retrusion, and mandibular protrusion using the
CBCT method.
Materials and Methods
Patient Follow-Up
The CBCT data, which constitute the material of
this study, were obtained from Dicle University
Faculty of Dentistry. Ethics committee compli-
ance report was obtained from I
∙
zmir Katip Çelebi
University Local Ethics Committee (decision no.
1118, dated December 24, 2020). The experimental
group of the study consisted of a total of 7 people
(3 women and 4 men) with ectodermal dysplasia,
and the control group consisted of 7 people (3
women and 4 men) with skeletal class I (ANB 0–4)
malposition.
The CBCT images that make up the experimen­
tal group were selected according to the following
criteria: diagnosed with ectodermal dysplasia, no
history of orthodontic treatment or orthognathic
surgery, and no history of adenoidectomy or ton­
sillectomy operations.
The CBCT images that make up the control
group were selected according to the following
criteria: no history of orthodontic treatment or or-
thognathic surgery, no history of adenoidectomy
or tonsillectomy surgery, no airway pathology or
craniofacial syndrome, no lack of large number of
teeth (n>4) (which can affect the vertical size), and
skeletal class I (ANB 0–4) malposition.
Points used in the study22:
• Orbitale (Or): middle and lowest point of the
infraorbital border
Volume 43, Number 3/June 2021 131
Effects of Ectodermal Dysplasia on the Oropharynx

4. • Porion (Po): the uppermost point of the ear
canal
• a: the most anterior point of the first cervical
vertebra
• b: the lowest and foremost point of the second
cervical vertebra
• c: the lowest and foremost point of the third
cervical vertebra
Reference planes used in the study23 (Figure 1):
• FH plane: the line passing through the Po and
Or points
• 1st plane: the plane parallel to the FH plane
and passing through point a
• 2nd plane: the plane parallel to the FH plane
and passing through point b
• 3rd plane: the plane parallel to the FH plane
and passing through point c
Metric measurements in sagittal and transversal
directions were made from the transversal planes
of the tomographic images taken at the mentioned
levels from the oropharynx region of the individ­
uals (Figures 2–4).
Statistical Analysis
The data were evaluated using SPSS statistics
package program (IBM SPSS Statistics for Win-
dows, Version 25.0, Released 2017, IBM Corp.,
Armonk, New York, USA). Descriptive statistics
given were as follows: number of individuals (n),
mean±standard deviation (x
-±SD), mean ranks,
and sum of ranks. The normality of the measure-
ment difference was evaluated with the Shapiro-
Wilk normality test. The nonparametric Mann-
Whitney U test was used to evaluate the mean
difference between two independent groups and
to determine the difference or equality between
the groups. In statistical values, a confidence inter-
val of 95% was used, and the results were consid­
ered statistically significant for p<0.05.
Results
According to the results of the nonparametric
Mann-Whitney U test performed between the con­
trol and ectodermal dysplasia groups, the differ­
ence between the groups’ width of the orophar-
ynx in the sagittal direction of the plane passing
parallel to the most anterior point of the first cer-
vical vertebra and intersecting the oropharynx was
statistically insignificant (p=0.338) (Table I).
The width of the oropharynx in the transversal
direction of the plane passing from the foremost
point of the first cervical vertebra parallel to the
Frankfurt horizontal plane and intersecting the
oropharynx was used to display the differences
between the control and ectodermal dysplasia
groups. As a result of the Mann-Whitney U test
analysis, no statistically significant difference was
found between the two groups (p=0.848) (Table I).
According to the results of the nonparametric
Mann-Whitney U test performed between the con­
trol and ectodermal dysplasia groups, the differ­
ence between the groups’ width of the orophar-
ynx in the sagittal direction of the plane passing
parallel to the lowest and most anterior point of
the second cervical vertebra and intersecting the
oropharynx was statistically insignificant (p=0.848)
(Table I).
The width of the oropharynx in the transver-
sal direction of the plane passing parallel to the
Frankfurt horizontal plane from the lower and
foremost point of the second cervical vertebra and
intersecting the oropharynx was used to display
the differences between the control and ectoder-
mal dysplasia groups. As a result of Mann-Whitney
U test analysis, there was no statistically signifi-
cant difference between the two groups (p=0.655)
(Table I).
According to the results of the nonparametric
Mann-Whitney U test performed between the con­
trol and ectodermal dysplasia groups, the differ­
ence between the groups’ width of the orophar-
ynx in the sagittal direction of the plane passing
parallel to the lowest and most anterior point of
the third cervical vertebra and intersecting the
132 Analytical and Quantitative Cytopathology and Histopathology®
Ünal
Figure 1 Reference planes.

5. oropharynx was statistically insignificant (p=0.848)
(Table I).
The width of the oropharynx in the transver-
sal direction of the plane passing parallel to the
Frankfurt horizontal plane from the lowest and
foremost point of the third cervical vertebra and
intersecting the oropharynx was used to display
the differences between the control and ectoder-
mal dysplasia groups. As a result of Mann-Whitney
U test analysis, there was no statistically signifi-
cant difference between the two groups (p=0.337)
(Table I).
As a result of statistical analysis, in the metric
measurements applied in all three sections taken
at sagittal and transversal levels, no statistically
significant difference was found between these
groups at any level or direction.
Discussion
There are findings that linear, area, and volume
measurements of the airway in sagittal and trans-
versal directions can be better examined on 3D
images obtained with CBCT,16,23,24 and there are
studies reporting that there is no difference.17,25,26
Anatomical findings were determined with CBCT
images, which allow three-dimensional examina­
tion of the airway.
Hyperdivergent individuals have a posterior
growth direction characterized by increased face
height and gonial angle. Adenoid obstruction was
found to be most common in long-faced individ­
uals.11 Opdebeeck et al27 reported that long-faced
patients have smaller nasopharyngeal cavities than
do short-faced patients. Therefore, only skeletal
class I patients with normal vertical relationship
were included in our study in order to eliminate
any effect on the airway caused by changes in the
vertical plane. Craniofacial features of patients with
ectodermal dysplasia show similarities to class III
individuals.
Di Carlo et al15 found no statistically significant
relationship between the transversal, sagittal, and
volumetric size and morphology of the upper air­
ways and skeletal malocclusions. The conclusion
Volume 43, Number 3/June 2021 133
Effects of Ectodermal Dysplasia on the Oropharynx
Figure 2
Sagittal and coronal views of
sections.
Figure 3
First, second, and third plane
sections on axial section.

6. that the differences in craniofacial morphology de-
termined by the sagittal relationship are not re-
lated to variations in upper airway volumes, and
that the transversal width increases through down­
wards, is consistent with our study.
Arslan et al,7 in their study using lateral cepha-
134 Analytical and Quantitative Cytopathology and Histopathology®
Ünal
Figure 4
First, second, and third plane
cross section measurements on
axial section.
Table I Comparison of Ectodermal Dysplasia and Control Groups with Mann-Whitney Test According to the Cross-Section and Direction
Variables and Their Findings
Sum Mann-
Mean of Whitney
Group N x
- SD ranks ranks U test p Value
1st plane
Sagittal plane 17 0.338
Ectodermal 7 11.87 1.78 6.43 45 NS
Dysplasia
Control 7 13.14 3.10 8.57 60
Transversal plane 23 0.848
Ectodermal 7 25.00 6.51 7.29 51 NS
Dysplasia
Control 7 26.02 5.04 7.71 54
2nd plane
Sagittal plane 23 0.848
Ectodermal 7 9.84 2.84 7.29 51 NS
Dysplasia
Control 7 9.70 2.46 7.71 54
Transversal plane 21 0.655
Ectodermal 7 23.77 8.71 7.00 49 NS
Dysplasia
Control 7 26.64 6.74 8.00 56
3rd plane
Sagittal plane 23 0.848
Ectodermal 7 12.58 5.23 7.29 51 NS
Dysplasia
Control 7 12.42 3.54 7.71 54
Transversal plane 17 0.337
Ectodermal 7 31.83 5.89 8.57 60 NS
Dysplasia
Control 7 28.30 5.59 6.43 45
P>0.05 was considered NS (nonsignificant), and p<0.05 was considered statistically significant.

7. lograms to compare airway sizes between patients
with ectodermal dysplasia and a control group,
reported that the ectodermal dysplasia group ex-
hibited smaller airway sizes. We could not find
any statistically significant difference (p>0.05) be-
tween the control group and the ectodermal dys­
plasia group as a result of the evaluation of the
oropharynx airway in CBCT images. The findings
of this study were not consistent with those of
Arslan et al.7 Possible reasons for this situation
can be listed as follows: (1) Arslan et al7 includ­
ed 10 patients with class III malocclusion in the
control group, whereas this study was composed
of normodivergent and skeletal class I individuals
in vertical and sagittal direction, and (2) since the
airway is a 3-dimensional structure, 2-dimensional
lateral cephalograms cannot be obtained, and there
are important limitations in its evaluation.
Significant association between pharyngeal mor­
phology with dentofacial and craniofacial struc­
tures has been reported in many studies.8,11,13,14,19,28
Emslie et al29 stated that skeletal features such as
maxillar and mandibular retrusion and vertical
maxillary excess in hyperdivergent individuals
may cause a narrower airway at the anteroposte-
rior distance. Ceylan et al11 found that there is a
significant relationship between pharyngeal di­
mensions and craniofacial anomalies and that
class III individuals have more oropharynx area
than do class II individuals; this is consistent with
the conclusion of Martin et al13 that lower pharynx
sizes increased in class III patients. However, the
common class 3 anomaly seen in patients with
ectodermal dysplasia is mostly caused by maxil-
lary retrusion, and we think that this may have
occurred (have been noticed) due to our exami-
nation of the oropharynx airway. Studies on the
nasopharynx will probably be beneficial. Working
on larger and more detailed groups in the future
will be useful in clarifying this issue.
Conclusion
As a result of precise measurements made on
three-dimensional images obtained by CBCT, there
was no significant difference in oropharyngeal
airway dimensions between the control and ecto-
dermal dysplasia groups. While there are a few
limited studies on lateral cephalometric radio­
graphs on this subject, no 3D study has been found.
By conducting studies covering more cases in
this area, multidisciplinary solution-oriented treat-
ments can be enriched by better understanding the
craniofacial relationships of ectodermal dysplasia
patients. By improving aesthetics, function, and
phonation of ectodermal dysplasia patients, their
complaints can be reduced and they can participate
more fully in social life.
Acknowledgements
We would like to thank Dicle University Faculty
of Dentistry and I
∙
zzet Yavuz for sharing the ec-
todermal dysplasia patient archive for the study,
and Ersin Uysal for statistical evaluation. The au-
thor would also like to express thanks to Oğuz
Öztoprak for invaluable contribution to knowledge
and Mehmet I
∙
rfan Karadede, Department of Or-
thodontics, I
∙
zmir Katip Çelebi University Dentistry
Faculty, for scientific advice.
Ethical Approval
The study protocol was approved by the Health
Research Ethics Board of I
∙
zmir Katip Çelebi Uni­
vesity, School of Medicine (ethics committee deci­
sion report no. 1118, dated December 24, 2020).
The study was conducted in accordance with the
principles of the Declaration of Helsinki. In this
research, CBCT images which were previously re-
corded for diagnostic and therapeutic purposes
were used from the archives of I
∙
zmir Katip Çelebi
University Faculty of Dentistry, Department of Ra­
diology. A written informed consent was obtained
from each participant.
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