Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860

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Cephalometric analysis of craniofacial morphology and growth in

unrepaired isolated cleft palate patients
Yi Xu a, Chao Yang b, Willem Hans Schreuder c, Jiayu Shi b, Bing Shi b, Qian Zheng b,
Yan Wang b, *
a
Capital Medical University School of Stomatology, Beijing 100050, China
b
Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, China
c
Department of Oral and Maxillofacial Surgery, Academic Medical Center/ACTA, University of Amsterdam, Amsterdam, The Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: Objective: The aim of this study is to analyze the craniofacial morphology in patients with unrepaired
Paper received 14 September 2013 isolated cleft palate (UICP) at childhood, adolescence and adulthood, in order to assess the influence of
Accepted 18 July 2014 nonsurgical factors on the craniofacial growth in these patients.
Available online 29 July 2014
Material and methods: Lateral and posteroanterior cephalograms of 106 non-syndromic UICP patients
and 102 normal matched controls were obtained and analyzed. Patients and controls were divided into
Keywords:
three subgroups: children (5e7 years), adolescents (12e14 years), and adults (>18 years).
Cleft palate
Results: UICP patients in childhood showed a shortened cranial basal length; reduced bony nasopha-
Growth and development
Skull
ryngeal height; short maxillary depth and height with a posterior positioned maxilla and an increased
width of the nasal cavity, maxilla and orbit; and a shortened mandibular length and height. UICP patients
in adulthood showed a normal nasopharyngeal and mandibular morphology. However, the patients in
this subgroup still showed a shortened cranial basal length, and short maxillary depth and anterior
height with increased width of the nasal cavity, maxilla and orbit.
Conclusions: Craniofacial morphology and growth in patients with UICP were significantly affected by
nonsurgical factors. Growth of the cranial base and upper face were absolutely reduced, while growth of
the bony nasopharynx and mandible were only postponed.
© 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights
reserved.

1. Introduction surgery should be eliminated. In that case, the unrepaired cleft

Restricted development of craniofacial structures is often seen
in patients with cleft palate. The causes of this limitation of growth
are still controversial. Some previous reports (Mars and Houston,
1990; Mazaheri et al., 1967; Ross and Coupe, 1965) attributed it to
previous surgical repairs. However, others (Bishara, 1973; Dahl,
1970; Smahel, 1984) introduced factors aside from surgical
manipulation (induced traits) that might play a role, such as: (1)
genetic pattern (inherited trait), and (2) adaptive changes resulting
from the mechanical presence of the cleft (acquired traits). In order
to analyze the adverse effects of these nonsurgical factors on
craniofacial growth and morphology, all variables introduced by
* Corresponding author.
E-mail addresses: xuyij10@sina.com (Y. Xu), wangyanscu@sina.com (Y. Wang).
patient is the most appropriate subject to be investigated.
In the past, many cephalometric studies have been performed
on craniofacial morphology in infants with unrepaired isolated cleft
palate (UICP). Bishara (1973); Dahl et al. (1982) and Hermann et al.
(2002) all found that infants with UICP showed a short maxilla, a
reduced posterior maxillary height, an increased posterior maxil-
lary width and nasal width, a short mandible, a reduced posterior
height of the mandible, and a reduced pharyngeal depth and
height.
However, relatively few studies have reported on adult patients
with UICP. Also, these few studies yielded inconsistent results.
Yoshida et al. (1992) found that UICP patients with a mixed
dentition had an almost normal craniofacial morphology, but pa-
tients with a permanent dentition showed a retruded maxilla, a
short hard palate, an inferior rotation of the mandible and a relative
maxillary retrusion. This is in contrast with the results of Atherton
(1967), concluding that some deformities, which were obvious in

http://dx.doi.org/10.1016/j.jcms.2014.07.003
1010-5182/© 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
1854 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860
young patients, were almost undetectable in adult patients.
Although the results are not consistent, the aberrant findings in
both reports do suggest a potential adverse effect of the nonsurgical
factors on craniofacial morphology. However, the question remains,
if there is a continuing intrinsic defect and craniofacial growth is
absolutely reduced, or if the influence is only temporary and
craniofacial growth is only postponed.
Fortunately, most patients with a cleft palate now undergo
surgery early in life (Bishara et al., 1986), and the number of in-
dividuals in late childhood or adulthood who have not had surgical
correction is rapidly diminishing in most areas of the world. On the
other hand, in order to accurately assess the influence of the
nonsurgical factors on craniofacial morphology and growth, not
only infants with UICP should be analyzed. Their observations
should be correlated with results of patients with UICP from older
age groups. Only in developing countries and remote areas where
early surgery is not readily available, there is still an opportunity to
examine a limited number of patients with unoperated cleft palates
at later stages of development. With the current lack of knowledge
in mind, study of these UICP patients may help us to understand the
influence of nonsurgical factors.
The purpose of this study is to analyze the craniofacial
morphology in children, adolescents and adults with UICP, in order
to assess the influence of the nonsurgical factors on the craniofacial
morphology and growth in these patients and in particular to
elucidate whether nonsurgical factors absolutely reduce craniofa-
cial growth or only postpone it.
2. Material and methods
2.1. Subjects
One hundred and six Chinese patients with a non-syndromic
unoperated isolated complete cleft of hard and soft palate (UICP)
from the southwest of China, who were referred for palatoplasty to
the Department of Cleft Lip and Palate, West China College of Sto-
matology, Sichuan University, served as subjects for this study.
Measurements of 102 normal southwestern Chinese, matched for
age and gender and with Angle class I occlusion without any
remarkable craniofacial deformities, served as controls for this
study. Patients were divided into three subgroups: child group
ranging from 5 to 7 years, adolescent group ranging from 12 to 14
years, and adult group older than 18 years (Table 1). Informed
consent was obtained from all patients and controls following
institutional review board approval.
2.2. Methods
Lateral and PA cephalograms of all patients and controls were
taken in the same cephalostat. Patients and controls were orien-
tated to the Frankfurt horizontal plane with teeth in occlusion. The
digital radiographs were analyzed directly with WenCeph 7.0 (Rise
Corporation, Sendai, Japan).
Table 1
Distribution of patients and controls according to age and sex.
Sex UICP Controls
Age (years) Male Female Male
5e7 12 24 11
12e14 14 26 14
>18 9 21 10
UICP: unrepaired isolated cleft palate.
The following landmarks were identified on each lateral ceph-
alogram: Ba, basion; S, sella; N, nasion; ANS, anterior nasal spine;
PNS, posterior nasal spine in controls; Pl, palatale (the most pos-
terior point of the palatal processes in UICP); Ptm, pterygomaxillary
fissure; Pmp, pterygomaxillarepalatinum (the intersection of the
palate plane with the pterygomaxillary fissure in UICP); Cd, con-
dylion; Go, gonion; Gn, gnathion; Pgn, prognathion; Pg, pogonion;
Ii, incisiorinferius; A, point A; B, point B (Fig. 1A) (Smahel, 1984). On
each PA cephalogram, the following landmarks were identified: Lo,
lateroorbitale (the intersection between the lateral margin of the
orbit and linea innominata); Apt, apertion (most lateral point of the
nasal cavity); Mo, medioorbitale (most medial point of the orbital
orifice); Mx, ectomaxillare (intersection of lateral contour of upper
alveolar process and lower contour of maxillozygomatic process of
maxilla); Zyg, zygion (most lateral points on the zygomatic arch)
(Fig. 1B) (Motohashi et al., 1994).
From these landmarks, various linear and angular measure-
ments were derived. The parameters used in this study were as
follows:
1 Cranial base: Anterior length (SeN), Posterior length (SeBa),
Total length (NeBa), Cranial base angle (NSBa)
2 Bony nasopharynx: Length in UICP (Pmp-Ba), Height in UICP
(Pmp-S); Length in controls (PNSeBa), Height in controls
(PNSeS)
3 Upper face: Maxillary depth in UICP (ANS-Pmp), Maxillary
depth in controls (ANS-PNS), Anterior height of the upper face
(N-ANS), Posterior height of the upper face in UICP (Pmp-NSL),
Posterior height of the upper face in controls (PNS-NSL),
Maxillary sagittal position (SNA); Upper facial width (LoeLo0 ),
Inter-orbital distance (MoeMo0 ), Mid-facial width (ZygeZyg0 ),
Nasal width (ApteApt0 ), Maxillary alveolar width (MxeMx0 )
4 The lower jaw: Mandibular body length (Gn-Go), Mandibular
ramus length (Cd-Go), Total mandibular length (Gn-Cd), Ante-
rior height of the mandible (Ii-Pgn), Mandibular sagittal Position
(SNB), Sagittal position of chin (SNPg); The angle of the
mandibular plane (SN/GoPgn); The angle between the palatal
plane and mandibular plane (ANSPmp/GoPgn in UICP
andANSPNS/GoPgn in controls); Bicondylar width (CdeCd0 ),
Bigonial width (GoeGo0 )
5 Maxillary mandibular relationship: ANB
The same investigator (Yi Xu) identified all landmarks and
derived all measurements twice, with an interval of two weeks. The
average value of each pair of measurements was used for statistical
analysis. Intra-observer concordances of four measurements
related to the Pmp (Pmp-Ba, Pmp-S, Pmp-NSL, and ANS-Pmp),
which were most likely to be affected by landmark identification,
were analyzed at the childhood age subgroup to investigate the
landmark identification reliability of this method.
2.3. Statistical analysis
Pearson correlation coefficients (Pearson r) were used to test
intra-observer concordance. A Student t-test was used to test the
significance of differences between same age subgroups of UICP
and controls and also between different age subgroups of UICP or
controls. The level of significance was set to 0.05.
3. Results
Female
21 The Pearson r coefficients of Pmp-Ba, Pmp-S, Pmp-NSL, and
26 ANS-Pmp were 0.996, 0.993, 0.990, and 0.994 for intra-observer
20 measurements suggesting high landmark identification reliability
of this method.
 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860 1855

Fig. 1. Cephalometric landmarks used for analysis in this study. (A) Lateral cephalogram; (B) PA cephalogram.

The craniofacial growth of patients with UICP is presented in 3.2. Bony nasopharynx
Table 2 and illustrated in Fig. 2. Results showed that craniofacial
structures in patients with UICP developed anteriorly, inferiorly, UICP patients had normal nasopharyngeal length (Pmp-Ba) and
and laterally, taking the sella and the sella-nasion line as references. significantly shortened nasopharyngeal height (Pmp-S) in
Starting from the childhood subgroup into the adult subgroup, the
mean angle between the cranial base and the mandibular plane Table 2
(SN/GoPgn) in UICP patients decreased gradually (p ¼ 0.002, Cephalometric measurements (Mean ± SD) and statistical comparisons of cranio-
p ¼ 0.032). This was the same for the angle between the palatal facial morphology in UICP patients ordered in different age subgroups.
plane and mandibular plane (ANSPmp/GoPgn) (p ¼ 0.007, 5e7 years 12e14 years ＞18 years p valuec
p ¼ 0.012). (Ⅰ) (Ⅱ) (Ⅲ)
Ⅰ vs. Ⅱ Ⅱ vs. Ⅲ
The craniofacial growth of controls is presented in Table 3 and
illustrated in Fig. 3. Results showed that craniofacial structures in Cranial base
SeNa 55.1 ± 1.9 58.1 ± 3.0 59.9 ± 3.3 0.002 0.048
normal controls also developed anteriorly, inferiorly, and laterally,
SeBa 39.8 ± 4.0 41.3 ± 3.1 43.0 ± 2.5 0.221 0.034
taking the sella and the sella-nasion line as references. However, NeBa 87.6 ± 4.5 90.7 ± 5.3 94.4 ± 5.0 0.080 0.010
the forward growth of craniofacial structures was unobvious after NSBa b
134.3 ± 6.4 131.2 ± 6.6 132.9 ± 6.3 0.175 0.342
adolescence (differences of SeN, ANS-PNS, SNA, SNB, SNPg be- Bony nasopharynx
Pmp-Ba 38.4 ± 4.0 40.4 ± 3.6 41.9 ± 3.6 0.127 0.145
tween adolescence and adulthood were insignificant, p ¼ 0.424,
Pmp-S 36.6 ± 3.2 43.1 ± 3.6 44.5 ± 3.2 <0.001 0.132
p ¼ 0.413, p ¼ 0.766, p ¼ 0.798, p ¼ 0.852). As in UICP patients, also Upper face
in the controls the angle SN/GoPgn decreased gradually (p ¼ 0.041, ANS-Pmp 35.9 ± 2.3 38.0 ± 3.5 39.1 ± 4.7 0.040 0.377
p ¼ 0.004). However, in this group the angle ANSPNS/GoPgn N-ANS 43.3 ± 2.8 47.1 ± 3.3 50.9 ± 3.8 0.001 <0.001
remained unchanged during development (p ¼ 0.244, p ¼ 0.063). Pmp-NSL 35.3 ± 3.0 41.4 ± 3.2 43.1 ± 3.0 <0.001 0.051
SNA 77.5 ± 3.3 80.2 ± 4.5 79.4 ± 4.7 0.049 0.550
When the angle SN/GoPgn was compared between cleft patients
LoeLo0 82.1 ± 5.0 81.9 ± 4.6 87.3 ± 4.5 0.947 <0.001
and their normal counterparts, a significant difference was only MoeMo0 19.7 ± 2.7 22.1 ± 2.8 25.2 ± 2.4 0.017 <0.001
found comparing the child subgroup (p ¼ 0.001) (Table 4). ApteApt0 31.7 ± 3.0 34.1 ± 4.5 37.3 ± 4.0 0.076 0.009
Considering the difference of the angle ANSPmp/GoPgn (ANSPNS/ MxeMx0 58.4 ± 3.7 59.9 ± 3.5 63.9 ± 4.4 0.223 0.001
0
GoPgn) between UICP patients and controls, the results demon- ZygeZyg 109 ± 5.3 114.1 ± 4.7 125.0 ± 8.1 0.005 <0.001
The lower jaw
strated that the angle was larger at childhood (p ¼ 0.004), equiv- Gn-Go 56.3 ± 3.6 65.5 ± 6.3 69.9 ± 6.3 <0.001 0.016
alent at adolescence (p ¼ 0.501) and smaller at adulthood Cd-Go 44.1 ± 3.5 47.4 ± 4.6 55.4 ± 5.3 0.025 <0.001
(p ¼ 0.035) in patients with UICP (Table 4). Gn-Cd 89.4 ± 3.6 99.8 ± 6.5 108.3 ± 7.3 <0.001 <0.001
The values of the landmark measurements to assess the Ii-Pgn 33.3 ± 1.9 36.0 ± 2.6 39.7 ± 3.2 0.002 <0.001
SNB 75.1 ± 3.1 79.1 ± 4.1 78.6 ± 5.4 0.004 0.750
craniofacial morphology in patients with UICP, compared with the
SNPg 74.8 ± 3.3 79.5 ± 4.3 79.3 ± 5.6 0.001 0.912
matched control group, are presented in Table 4. Mean facial dia- SN/GoPgn 41.3 ± 3.0 36.5 ± 4.2 33.7 ± 3.6 0.002 0.032
grams illustrating the craniofacial morphology of patients with ANSPmp/GoPgn 30.4 ± 2.8 28.1 ± 3.7 26.3 ± 3.2 0.007 0.012
UICP and controls at childhood, adolescence and adulthood are CdeCd0 91.4 ± 3.9 93.9 ± 4.2 102.9 ± 7.1 0.077 <0.001
showed in Figs. 4e6. GoeGo0 79.4 ± 5.5 82.9 ± 5.2 92.0 ± 6.4 0.064 <0.001
Maxillary mandibular relationship
ANB 2.4 ± 2.3 1.1 ± 3.0 0.8 ± 3.6 0.169 0.733

3.1. Cranial base
UICP patients in childhood, adolescence and adulthood all
showed significantly shortened cranial basal lengths (SeN, SeBa,
and NeBa), while the cranial base angle was normal in all UICP
subgroups (p ¼ 0.244, p ¼ 0.680, p ¼ 0.492).
ANS, anterior nasal spine; Apt, apertion; Ba, basion; Cd, condylion; Go, gonion; Gn,
gnathion; Ii, incisiorinferius; Lo, lateroorbitale; Mo, medioorbitale; Mx, ectomax-
illare; N, nasion; Pg, pogonion; Pgn, prognathion; Pl, palatale; Pmp, pterygomax-
illarepalatinum; PNS, posterior nasal spine in controls; Ptm, pterygomaxillary
fissure; S, sella; Zyg, zygion.
a
Distances between two landmarks were measured in millimeters (mm).
b
Angles formed by three landmarks were measured in degrees.
c
The threshold of significance was set at p ¼ 0.05.
1856 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860

Fig. 2. Mean facial diagrams illustrating the craniofacial growth of patients with UICP in childhood (solid line), adolescence (broken line) and adulthood (dotted line). (A) Lateral
diagram; (B) PA diagram. The lateral diagram is orientated along the sella-nasion line and registered at sella, and the PA diagram is orientated along the MoeMo0 line and registered
at the middle of bilateral medioorbitale.

childhood. In the adolescent subgroup, both length and height In the adolescent subgroup, the position of the maxilla in the
were shortened. However, for the adult UICP patients both mean mediosagittal plane was normal (SNA, p ¼ 0.318), but the maxillary
values were normal compared with the control group (p ¼ 0.180, depth, anterior and posterior maxillary height were shortened. The
p ¼ 0.172). adult UICP patients also showed shortened maxillary depth and
anterior maxillary height, while the maxillary sagittal position
(SNA, p ¼ 0.060) and posterior maxillary height (Pmp-NSL,
3.3. Upper face p ¼ 0.263) were normal compared with their control counterparts.
PA cephalometry showed that UICP patients in childhood,
UICP patients showed significantly shortened maxillary depth adolescence and adulthood all had significantly widened upper
(ANS-Pmp), anterior maxillary height (N-ANS), posterior maxillary facial width (LoeLo0 ), inter-orbital distance (MoeMo0 ), nasal width
height (Pmp-NSL), and retrusion of the maxilla (SNA) in childhood. (ApteApt0 ), and maxillary alveolar width (MxeMx0 ). The mid-facial
width (ZygeZyg0 ) was normal in all age groups (p ¼ 0.532,
p ¼ 0.295, p ¼ 0.571).
Table 3
Cephalometric measurements (Mean ± SD) and statistical comparisons of cranio-
facial morphology in controls ordered in different age subgroups. 3.4. The lower jaw
c
5e7 years 12e14 years ＞18 years p value
(Ⅰ) (Ⅱ) (Ⅲ) UICP patients showed significantly shortened mandibular body
Ⅰ vs. Ⅱ Ⅱ vs. Ⅲ
length (Gn-Go), mandibular ramus length (Cd-Go), total mandib-
Cranial base ular length (Gn-Cd), and anterior mandibular height (Ii-Pgn) in
SeNa 57.9 ± 2.3 61.8 ± 2.9 62.4 ± 3.5 <0.001 0.424
childhood. In the adolescent subgroup, the mandibular ramus
SeBa 40.9 ± 2.7 45.5 ± 2.9 47.6 ± 2.9 <0.001 0.002
NeBa 90.6 ± 3.5 97.7 ± 4.6 97.9 ± 5.0 <0.001 0.865
length, total mandibular length, and anterior mandibular height
NSBab 132.5 ± 4.8 130.7 ± 4.7 132.0 ± 5.2 0.066 0.242 were also shortened, while the mandibular body length was normal
Bony nasopharynx (p ¼ 0.061). In the adult UICP patient, except for the mandibular
PNS-Ba 40.0 ± 3.1 43.1 ± 3.3 43.1 ± 3.9 <0.001 0.991 ramus length, mandibular body length (p ¼ 0.487), total mandib-
PNS-S 41.1 ± 2.7 45.7 ± 3.4 45.6 ± 3.3 <0.001 0.949
ular length (p ¼ 0.745), and anterior mandibular height (p ¼ 0.468)
Upper face
ANS-PNS 42.5 ± 2.4 45.5 ± 2.6 46.0 ± 3.0 <0.001 0.413 were normal. Sagittal position of mandible (SNB, p ¼ 0.328,
N-ANS 46.0 ± 2.3 51.1 ± 2.9 53.0 ± 3.2 <0.001 0.009 p ¼ 0.351, p ¼ 0.561) and chin (SNPg, p ¼ 0.218, p ¼ 0.354,
PNS-NSL 39.4 ± 2.6 43.9 ± 3.2 43.9 ± 3.1 <0.001 0.954 p ¼ 0.448) were normal in all three age groups.
SNA 80.4 ± 3.2 81.2 ± 3.4 81.4 ± 3.9 0.254 0.766 PA cephalometry showed that UICP patients in childhood,
0
LoeLo 73.9 ± 3.7 77.8 ± 3.6 81.8 ± 3.1 <0.001 <0.001
MoeMo0 17.9 ± 2.2 21.4 ± 2.6 23.4 ± 2.0 <0.001 0.001
adolescence and adulthood had normal mean values for bicondylar
ApteApt0 25.7 ± 2.8 29.9 ± 2.6 31.4 ± 2.6 <0.001 0.020 width (CdeCd0 , p ¼ 0.937, p ¼ 0.736, p ¼ 0.407), and bigonial width
MxeMx0 52.7 ± 4.2 57.9 ± 3.1 57.7 ± 2.8 <0.001 0.764 (GoeGo0 , p ¼ 543, p ¼ 0.579, p ¼ 0.171).
ZygeZyg0 107.8 ± 6.6 115.6 ± 5.6 124.0 ± 5.5 <0.001 <0.001
The lower jaw
Gn-Go 61.8 ± 4.5 68.5 ± 4.6 70.8 ± 4.4 <0.001 0.031 3.5. Maxillary mandibular relationship
Cd-Go 46.7 ± 3.5 52.8 ± 4.7 58.0 ± 4.5 <0.001 <0.001
Gn-Cd 93.9 ± 5.0 104.9 ± 5.9 108.9 ± 6.1 <0.001 0.004 All UICP patients showed a relative maxillary retrusion in
Ii-Pgn 34.7 ± 1.8 38.0 ± 2.2 40.3 ± 3.4 <0.001 <0.001 childhood, adolescence and adulthood (ANB, p ¼ 0.004, p ¼ 0.013,
SNB 76.2 ± 3.6 78.2 ± 3.5 78.0 ± 3.8 0.006 0.798
SNPg 76.2 ± 3.8 78.6 ± 3.4 78.4 ± 3.8 0.001 0.852
p < 0.001).
SN/GoPgn 37.2 ± 4.1 35.5 ± 3.2 32.8 ± 3.7 0.041 0.004
ANSPNS/GoPgn 28.6 ± 3.8 28.2 ± 3.0 27.4 ± 3.2 0.244 0.063 4. Discussion
0
CdeCd 91.5 ± 5.3 93.4 ± 5.3 101.6 ± 6.6 0.144 <0.001
GoeGo0 78.1 ± 7.2 82.2 ± 4.4 89.9 ± 5.6 0.011 <0.001
Maxillary mandibular relationship The final aim of this study was to provide more insight into the
ANB 4.2 ± 2.0 3.0 ± 1.6 3.5 ± 1.8 0.001 0.241 natural development and morphology of craniofacial structures in
a
Distances between two landmarks were measured in millimeters (mm).
isolated cleft palate patients, by excluding external influencing
b
Angles formed by three landmarks were measured in degrees. factors such as surgery or other treatment manipulations. There-
c
The threshold of significance was set at p ¼ 0.05. fore, a cohort of patients with an isolated complete cleft of the
 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860 1857

Fig. 3. Mean facial diagrams illustrating the craniofacial growth of controls in childhood (solid line), adolescence (broken line) and adulthood (dotted line). (A) Lateral diagram; (B)
PA diagram.

secondary palate with no surgical correction from different age
groups was studied and compared with a cohort of matched normal
counterparts. Most former studies conducted on individuals with
unoperated clefts had one or more of the following shortcomings:
small sample size; wide age distribution; mixture of unoperated,
partially operated, and late operated individuals; and a mixture of
individuals with different cleft types (Bishara et al., 1986). To obtain
more reliable data, this study tried to avoid these methodological
limitations. However, as mentioned earlier, the rather limited
number of available subjects to study with UICP, especially for the
older age subgroups, has become insurmountable.
In general, UICP patients showed similar craniofacial growth
rhythm and direction to normal individuals, except for the forward
growth after adolescence. As craniofacial structures in UICP pa-
tients continued to develop anteriorly into adulthood, the forward
growth of craniofacial structures after adolescence was unobvious
in normal individuals.
The cranial base values for UICP patients demonstrated a normal
cranial base angle (NSBa) similar to the control group, with short-
ening of the pre- and postsellar length (SeN, SeBa, and NeBa) in all
three age groups. This is in agreement with previous observations
(Dahl et al., 1982; Hermann et al., 2002; Mølsted et al., 1995). From
these findings, it could be concluded that growth and development

Table 4
Cephalometric measurements and statistical comparisons of craniofacial morphology between UICP patients and controls ordered in different age subgroups.

5e7 years 12e14 years ＞18 years

UICP Control pc UICP Control p UICP Control p

Cranial base
SeNa 55.1 57.9 <0.001 58.1 61.8 <0.001 59.9 62.4 0.004
SeBa 39.8 40.9 0.227 41.3 45.5 <0.001 43.0 47.6 <0.001
NeBa 87.6 90.6 0.009 90.7 97.7 <0.001 94.4 97.9 0.006
NSBab 134.3 132.5 0.244 131.2 130.7 0.680 132.9 132.0 0.492
Bony nasopharynx
Pmp(PNS)eBa 38.4 40.0 0.108 40.4 43.1 0.003 41.9 43.1 0.180
Pmp(PNS)eS 36.6 41.1 <0.001 43.1 45.7 0.007 44.5 45.6 0.172
Upper face
ANS-Pmp(PNS) 35.9 42.5 <0.001 38.0 45.5 <0.001 39.1 46.0 <0.001
N-ANS 43.3 46.0 <0.001 47.1 51.1 <0.001 50.9 53.0 0.018
Pmp(PNS)-NSL 35.3 39.4 <0.001 41.4 43.9 0.004 43.1 43.9 0.263
SNA 77.5 80.4 0.004 80.2 81.2 0.318 79.4 81.4 0.060
LoeLo0 82.1 73.9 <0.001 81.9 77.8 <0.001 87.3 81.8 <0.001
MoeMo0 19.7 17.9 0.018 22.1 21.4 0.344 25.2 23.4 0.002
ApteApt0 31.7 25.7 <0.001 34.1 29.9 0.001 37.3 31.4 <0.001
MxeMx0 58.4 52.7 <0.001 59.9 57.9 0.032 63.9 57.7 <0.001
ZygeZyg0 109 107.8 0.532 114.1 115.6 0.295 125.0 124.0 0.571
The lower jaw
Gn-Go 56.3 61.8 <0.001 65.5 68.5 0.061 69.9 70.8 0.487
Cd-Go 44.1 46.7 0.013 47.4 52.8 <0.001 55.4 58.0 0.032
Gn-Cd 89.4 93.9 0.002 99.8 104.9 0.002 108.3 108.9 0.745
Ii-Pgn 33.3 34.7 0.012 36.0 38.0 0.003 39.7 40.3 0.468
SNB 75.1 76.2 0.328 79.1 78.2 0.351 78.6 78.0 0.561
SNPg 74.8 76.2 0.218 79.5 78.6 0.354 79.3 78.4 0.448
SN/GoPgn 41.3 37.2 0.001 36.5 35.5 0.424 33.7 32.8 0.433
ANSPmp(ANSPNS)/GoPgn 30.4 28.6 0.004 28.1 28.2 0.501 26.3 27.4 0.035
CdeCd0 91.4 91.5 0.937 93.9 93.4 0.736 102.9 101.6 0.407
GoeGo0 79.4 78.1 0.543 82.9 82.2 0.579 92.0 89.9 0.171
Maxillary mandibular relationship
ANB 2.4 4.2 0.004 1.1 3.0 0.013 0.8 3.5 <0.001
a
Distances between two landmarks were measured in millimeters (mm).
b
Angles formed by three landmarks were measured in degrees.
c
The threshold of significance was set at p ¼ 0.05.
1858 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860

Fig. 4. Mean facial diagrams illustrating the craniofacial morphology of patients with UICP (broken line) and controls (solid line) in childhood. (A) Lateral diagram; (B) PA diagram.
The lateral diagram is orientated along the sella-nasion line and registered at sella, and the PA diagram is orientated along the MoeMo0 line and registered at the middle of bilateral
medioorbitale.

Fig. 5. Mean facial diagrams illustrating the craniofacial morphology of patients with UICP (broken line) and controls (solid line) in adolescence.

of the cranial base in UICP patients were proportionally reduced.
The association between the abnormal cranial base morphology
and cleft palate can be explained both anatomically and function-
ally. Anatomically, the cranial base can be considered as a border
structure between the neurocranium and the facial skeleton. Thus,
development and growth of the cranial base may interact with both
neurocranial and facial skeletal development (Mølsted et al., 1995).
Also, as the sphenooccipital synchondrosis represents remnants of
the early chondrocranium, it is possible that an inborn alteration,
an aberrant growth, or delayed maturation of the cartilage tissue
may affect the cranial base (Müller and O'Rahilly, 1980). Function-
ally, factors such as extended head posture caused by reduced size
of the airway, may also affect the postnatal growth pattern of the
cranial base in subjects with ICP (Hermann et al., 2002).
Length and height of the bony nasopharynx in children and
adolescents with UICP were shortened. Similar results were
observed in Hermann's study (Hermann et al., 2002). As previous
studies did not clearly assess the craniofacial morphology in adult
patients with UICP, it was unknown whether the deformities pre-
sent in childhood and adolescence were more or less maintained or

Fig. 6. Mean facial diagrams illustrating the craniofacial morphology of patients with UICP (broken line) and controls (solid line) in adulthood.
 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860
disappeared during development into adulthood. The present
study demonstrated that the morphology of the bony nasopharynx
was normal in adult patients. Therefore, it may be concluded that
the growth and development of the bony nasopharynx in UICP
patients was postponed, and the patient will eventually show
normal nasopharyngeal morphology reaching adulthood. This co-
incides with the ideas of Van Limborgh (1964), who reported that
the growth processes in cleft individuals proceed more slowly than
in normal individuals, but that the intrinsic growth potential is
essentially the same except for the cleft region.
The data in this study demonstrated that the upper facial
morphology in UICP patients was significantly different from
normal healthy individuals in all transverse (LoeLo0 , MoeMo0 ,
ApteApt0 ,MxeMx0 ), vertical (N-ANS) and sagittal (ANS-Pmp) di-
mensions during the entire process of development. Only posterior
upper facial height (Pmp-NSL) and sagittal position of the maxilla
related to the cranial base (SNA) eventually showed normal values
in adulthood. The comparison of these results with those reported
by some other authors disclose some differences as well as simi-
larities. Hermann et al. (2002) and Smahel et al. (1987) also found
increased width of the nasal cavity, reduced posterior maxillary
height and a short maxilla in infants with UICP, but they didn't find
any widening occurring away from the cleft region, such as this
study found in the orbital region (LoeLo0 , MoeMo0 ). Again, they
didn't present any data on the change of these deformities during
further craniofacial development. According to the present study, it
can be concluded that the growth and development of the upper
face in UICP patients was absolutely reduced during the entire
process of development. The possible reason for the abnormal
upper facial morphology in the UICP patient might be similar to
that in the untreated cleft lip and palate patient, which has been
discussed by Nielsen et al. (2005). In their opinion, cleft individuals
had a high incidence of deviations of sella turcica morphology,
which is a key point for the migration of neural crest cells to the
frontonasal and maxillary development fields. This abnormal sella
turcica might induce abnormal frontonasal and maxillary
morphology. Another reason for abnormal facial morphology in the
UICP patient could be the separation of the palate from the nasal
septum, which has been described by Smahel and Brejcha (1983)
and Scott (1953).
Although growth and morphology of the mandible in patients
with UICP were also affected, the impact of nonsurgical factors on
growth of the mandible was milder than for the maxilla. Cepha-
lometric measurements for transverse width (CdeCd0 , GoeGo0 )
and sagittal position of the mandible related to the cranial base
(SNB, SNPg) were normal in all subgroups and do not therefore
seem to be influenced during the entire process of growth. Pa-
tients in childhood showed a shortened mandibular body length
(Gn-Go), ramus length (Cd-Go), total length (Cd-Gn), and anterior
mandibular height (Li-Pgn). In the adolescent subgroup,
mandibular body length was comparable with the control group
and therefore seems to develop to normal length. Also total length
and anterior height seem to catch up later in the growth process,
as the values for the adult subgroup were normal. For adult pa-
tients in this study only the ramus length was found to be
abnormal. These results are in accordance with the study of
Smahel et al. (1987), but only partially agree with Hermann's re-
sults (Hermann et al., 2002). Smahel et al. (1987) also found a
normal sagittal position of the mandible (SNB) and smaller length
of the mandible for children with UICP, compared with their
normal counterparts. In agreement with our results Hermann
et al. (2002) found the length of the mandible to be significantly
reduced in children with UICP, but in their study the bigonial
width was decreased and the mandible was significantly retro-
gnathic (SNB). Again to be mentioned, the shortcoming of these
1859
two references was the lack of adult patients with UICP. Dahl et al.
(1982) ascribed the abnormal morphology of the mandible to
hypoplasia of the mandibular arch cartilage of the embryo. As the
current study found almost every parameter of the mandible to be
normal in adults, the etiology of different mandibular morphology
and development was not arch cartilage hypoplasia. It is hy-
pothesized to be secondary to the abnormal development of the
maxilla. Smahel (1984) also believed that changes of the
mandibular shape represented an adaptation secondary to the
cleft palate. Concluding from this study, the growth and devel-
opment of the mandible in UICP patients was postponed, and the
patient will eventually show normal mandibular morphology in
adulthood.
As the angle of the mandibular plane in relation to the cranial
base (SN/GoPgn) decreased gradually both in UICP patients and
controls, it meant that the dominant facial growth pattern of both
cleft patients and controls was expressed as a clockwise rotation.
However, by comparing the angle SN/GoPgn between patients with
UICP and controls, we found that the craniofacial growth rate was
different between both groups. There was a significant difference
between both childhood subgroups, as for this age category the
angle SN/GoPgn in cleft patients was larger than in controls. This
difference was not found between the adolescent or the adult
subgroups. This observation would indicate a higher growth rate in
UICP patients compared with their normal counterparts.
Furthermore, by analyzing the angle ANSPmp/GoPgn (ANSPNS/
GoPgn) between patients with UICP and controls, the UICP patient
developed a less divergent skeletal growth pattern compared with
their normal counterparts during development. In our opinion, this
might partly be ascribed to the disharmonious growth of the
maxilla and mandible. In UICP patients, the mandible had the
ability to catch up growth, while the growth of the maxilla
remained restricted. Therefore, the angle between the palatal plane
and mandibular plane became continuously smaller.
Macari et al. (2012) reported that the different types of growth
patterns go hand in hand with different dimensions of the naso-
pharynx. This is in accordance with our results. Compared with
their normal counterparts, UICP patients developed a less divergent
skeletal growth pattern during development; at the same time the
nasopharynx dimensions in the UICP patients suggest catch-up
growth as these develop to normal values.
Considering the maxillo-mandibular relationship, a relative
maxillary retrusion (ANB) was found in the present study. This
finding disagreed with Bishara's and Hermann's studies (Bishara,
1973; Hermann et al., 2002). In their studies, patients with UICP
showed a ‘normal’ face. This discrepancy may be attributed to
different findings on sagittal growth and position of the mandible.
Ideally, to be able to draw definite conclusions about craniofacial
growth, the same patient population would have to be followed
during the entire process of development starting from childhood.
However, nowadays it would be unethical to withhold surgery from
children with a cleft palate until they have reached adulthood.
Therefore, observations from matched patient samples in different
age groups, as described in this study, are the best possible way to
approximate the intrinsic growth potential in UICP patients.
5. Conclusion
Craniofacial morphology and growth in patients with UICP were
significantly affected by nonsurgical factors. The growth of the
cranial base and upper face were absolutely reduced, as UICP pa-
tients in adulthood still showed shortened cranial basal length, and
shortened anterior height and depth of maxilla with increased
width of the nasal cavity, maxilla and orbit. However, the growth of
the bony nasopharynx and mandible were only postponed, as UICP
1860 Y. Xu et al. / Journal of Cranio-Maxillo-Facial Surgery 42 (2014) 1853e1860
patients in adulthood showed normal nasopharyngeal and
mandibular morphology.
Conflict of interest
The authors declare that this study did not have any financial
support and that there are no conflicts of interest.
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