Case report Med Ultrason 2018, Vol. 20, no.

4, 531-535
DOI: 10.11152/mu-1582

Prenatal diagnosis of cleft lip and cleft lip palate – a case series
Claudiu Mărginean1,2, Vlăduț Săsăran2, Cristina Oana Mărginean3, Lorena Elena Meliț3,
Maria Oana Mărginean2,3

1Obstetrics and Gynecology Department, 2University of Medicine and Pharmacy Târgu Mureș, 3Pediatrics Depart-

ment, Târgu Mureș, Romania,

Abstract
Aim: Orofacial clefts comprise cleft lip (CL) or cleft lip-palate (CLP) and are the most frequently encountered malforma-
tion of the facial region, accounting for approximately 1-2.2/1,000 live births. The aim of this study was to reveal the particu-
larities regarding the prenatal diagnosis of orofacial clefts in a series of 11 cases diagnosed in a tertiary center. Material and
methods: The study was performed in a tertiary diagnostic center for a period of 8 years (January 2010 – December 2017), on
8125 patients that were assessed for screening or suspicion of malformations. Results: During the assessed period a number of
11 fetuses (0.13%) were diagnosed by 2D and 3D ultrasound with CL (4 cases) or CLP (7 cases). The smallest gestational age
at diagnosis was of 14 weeks, whereas the highest was 35 weeks. Of the 7 cases diagnosed with CLP, 4 presented also other
associated anomalies that involved the central nervous system, the kidney, the skeleton and the stomach. All 4 cases of CL had
identifiable associated anomalies. Termination of pregnancy was encountered in 3 cases with CLP. Conclusions: CLP can be
diagnosed even at the end of the 1st trimester of pregnancy. CL is usually diagnosed during the 2nd trimester ultrasound exam
and is commonly an isolated anomaly.
Keywords: cleft lip; cleft lip palate; ultrasound; prenatal diagnosis

Introduction
Orofacial clefts comprise of cleft lip (CL) or cleft lip-
palate (CLP) and are the most frequently encountered
malformation of the facial area that develop during the
6th-8th week of the intrauterine life. They represent also
the second most common birth defects [1,2]. The etiol-
ogy of these malformations involves multiple factors.
Genetic predisposition and fetal exposure to teratogenic
factors during the 2nd and the beginning of the 3rd month
are the most commonly incriminated triggers for these
malformations [3,4]. The worldwide incidence of orofa-
cial clefts varies between 1-2.2/1,000 live births, whereas
the prevalence depends on the geographic area and eth-
Received 13.05.2018 Accepted 14.06.2018
Med Ultrason
2018, Vol. 20, No 4, 531-535
Corresponding author: Săsăran Vlăduț
University of Medicine and Pharmacy
38 Gheorghe Marinescu street
540139 Tîrgu Mureș, Romania
Phone: +40-741-930348, Fax: +40-265-211098
E-mail: vlad.sasaran0403@gmail.com
nic features and ranges from 1:500 to 1:2,500 live births
[5–7]. These types of clefts can be encountered isolated
or as a part of other genetic syndromes. Approximately
one third of these orofacial malformations are associ-
ated with other anomalies, such as the central nervous
system, heart or limbs, ones that can threaten life it-
self [8,9]. Additionally, it is well-documented that CLP
(80%) are more commonly associated with other birth
defects (37%) [10,11]. Among these genetic and chro-
mosomal anomalies associated with CLP are: trisomy 13
and 18, triploidy, and other syndromes such as Golden-
har, Treacher-Collins, Sticklers, Pierre-Robin, DiGeorge,
Meckel-Gruber, Nager, Gorlin, Hydrolethalus, oro-fa-
cial-digital type 1 and 2, and Van der Woude [12].
The so called primary palate is formed by the lips,
the jaw, the nasal bone, while the secondary palate in-
volves the hard (behind and horizontally of the incisive
foramen) and soft palate (behind the hard palate, ends in
the uvula) [13]. The clefts of the primary and secondary
palates have a different embryological origin. Thus, the
primary palate clefts are a result of the fusion failure of
the medial nasal process and maxillary swellings [14],
532 Claudiu Mărginean et al
while the secondary clefts are due to a failure of fusion
of the two palatine shelves and are always in midline and
posterior to the incisive foramen [13]. Therefore, the sec-
ondary palate defects can include or not a defect of the
soft palate. During the gestational age of 10-12 weeks,
the ossification of the visceral cranium is complete.
The prenatal diagnosis is usually easier in the case of
CL and CLP compared to isolated cleft palate (CP) anom-
alies. The sonographic assessment of the palate structures,
especially the soft palate ones is very hard, even for an
experienced physician in prenatal ultrasonography. There-
fore, orofacial clefts have been reported to be diagnosed
usually during the 2nd and 3rd trimester of pregnancy based
on the mid sagittal, coronal and axial views of the fetal
face and head [15,16]. Even in case of combined two-di-
mensional (2D) and three-dimensional (3D) assessments,
the detection of these malformations has been rarely de-
scribed. Therefore, a screening study at 11-13 gestational
weeks performed on over 45,00 pregnancies concluded
that the prenatal diagnosis of isolated CLP was positive in
only 5% of fetuses that were born with this anomaly [17].
Transabdominal ultrasound should always represent the
first approach, but it can be improved by transvaginal ex-
amination in case of inconclusive images. A multidiscipli-
nary team involved in the care of a patient diagnosed with
orofacial clefts should involve specialists in an obstetrics,
genetics, neonatology, pediatrics, radiology, oral and max-
illofacial surgery and medical ethics. The prognosis of the
newborn diagnosed with this malformation depends on
both the accuracy of the prenatal diagnosis and the pres-
ence of other associations. CLP with the involvement of
soft palate and uvula leads to deglutition and phonation
disorders that are difficult to be repaired, while isolated CL
presents esthetical implications. Prenatal genetic testing
could be useful in predicting the recurrence rate of clefts.
Table I. The types of cleft syndrome in our series
Case Cleftmalformationtype
number
1 Large CLP that involves palate and uvula
2 CLP with soft palate involvement
3 Medial, unilateral CL
4 CLP with a normal uvula
5 CLP with the involvement of soft palate and uvula
6 CLP with soft palate involvement
7 Medial, unilateral CL
8 CLP without the involvement of uvula
9 Medial, unilateral CL
10 Medial, unilateral CL
11 CLP without the involvement of uvula
CL – cleft lip; CLP – cleft lip and palate; TOP – termination of pregnancy; QF PCR – quantitative fluorescence polymerase chain reaction
Prenatal diagnosis of cleft lip and cleft lip palate
The aim of this study was to reveal the particularities
regarding the prenatal diagnosis of orofacial clefts (the
gestational age at diagnosis, the type and the presence of
other associations) in a series of 11 cases diagnosed in a
tertiary center.
Material and method
The study was performed in a tertiary diagnostic
center for a period of 8 years (January 2010 – December
2017), on 8125 fetuses that were assessed for screening
of malformations or suspicion of orofacial malforma-
tions. The inclusion criteria comprised all the pregnan-
cies that were referred to our center for screening or for
the suspicion of a malformation, while the exclusion cri-
teria consisted of the refusal of the ultrasound exam. The
ultrasound exams were performed with Acuson S 2000,
or Voluson E8 or Voluson E10 machines. The exams
were done by 2D ultrasound with sagittal, coronal and
axial planes for the face and additional 3D with multipla-
nary reconstruction and surface rendering.
The informed consent was obtained from the mothers
for the publication of these cases.
Results
During the assessed period of 8 years, of all 8125
pregnancies included in our study, a number of 11 fetuses
(0.13%) were diagnosed by 2D and 3D ultrasound with
CL (4 cases) or CLP (7 cases). Establishment of the cleft
type through ultrasound, gestational age at the time of the
diagnosis and associated malformations are described in
table I. The ultrasound images of CLP are illustrated in
figures 1 and 2 while the ultrasound images of CL are
exemplified in figures 3 and 4.
Gestationalage at Associateanomalies or TOP
diagnosis (weeks)
14 TOP, QF PCR of the aborted fetus ruled out
trisomy 13, 18, 21
19 Fetal, symetrical hypotrophy, absence of the
stomach, bilateral pelvicalyceal dilations, TOP
19 –
20 –
21 Hydrocefaly, absence of cerebellum, TOP
23 –
23 –
25 Bordeline cerebral ventriculomegaly
31 –
32 –
35 Polycystic kidney

Fig 1. Cleft lip-palate; abnormal 2D facial pro-
file at 14 gestational weeks
Fig 2. Cleft lip-palate; axial 2D section at 14
gestational weeks
Discussions
Fetal malformations present multidisciplinary in-
volvements regarding the diagnosis, the therapeutic ap-
proach and the prognosis [18–28]. Therefore, prenatal
diagnosis is the cornerstone factor that can influence
the prognosis of these fetuses. Orofacial clefts, the most
common congenital malformations of all orofacial mal-
formations, can be diagnosed during the intrauterine
life due to the routine ultrasound scanning at different
gestational ages. Even though, the prenatal diagnosis
is usually established during the 2nd an 3rd trimester of
pregnancy [15,16], a more recent study has shown that
different ultrasound signs can predict orofacial clefts
even earlier, between 11 and 13 gestational weeks [17].
Regarding the gestational age at diagnosis in our cases
ranged between 14 and 35 gestational weeks, but gener-
ally below the gestational age of 25 weeks. Thus, only 3
cases of all 11 were diagnosed after this gestational age.
Also, it was reported in the literature that the half left
side in medial part is more frequently encountered to be
affected by orofacial clefts [29,30]. All our 11 cases pre-
sented a medial involvement. The prenatal diagnosis is
much easier for orofacial clefts that involve the lip and
the palate. When the lips are normal and the cleft involve
Med Ultrason 2018; 20(4): 531-535 533
Fig 3. Cleft lip; coronal 2D section at 19 ges-
tational weeks
Fig 4. Cleft lip; surface 4D rendering at 19 ges-
tational weeks
just the palate, the diagnosis is more difficult [31]. Our
series involved 4 cases of CL and 7 cases of CLP. Among
the 7 cases of CLP, 4 associated the involvement of soft
palate and uvula, worsening significantly the prognosis
of these cases and augmenting the importance of an ac-
curate prenatal diagnosis. Additionally, the earliest ges-
tational age at diagnosis was also noticed in a case with
CLP. It is also true that 4 of the 7 cases of CLP identified
in our series presented other associated malformations, a
fact that might have enhanced the accuracy of the diag-
nosis. On the other hand, all cases of CL diagnosed in our
study presented no associated anomalies being classified
as isolated CL. Our results are similarly to those reported
in the literature underlining a more frequent association
between CLP and a higher number of minor defects and
syndromes [32]. The most common associated anomalies
with CL and/or palate involve those of skeleton and neu-
ral tube defects [1,8,9]. Of our 4 CLP cases that presented
associated anomalies, we also encountered 2 cases with
central nervous system involvement, 2 cases with kid-
ney impairment, 1 case with skeleton defects, but we also
found a case with the absence of a stomach.
Regarding the prenatal ultrasound, multiple tech-
niques were proved to improve the diagnosis. Therefore,
a three-point multiplanar technique during a routine ul-
534 Claudiu Mărginean et al
trasound screening can result in a diagnosis rate of 65%
or even more of facial clefts at the 2nd trimester scan [12].
In addition, in the case of CL and/or alveolar ridge detec-
tion, 2D ultrasound improved by 3D can lead to a diag-
nosis of a cleft of the hard palate in more than 90% of the
cases [12]. Moreover, very recent data suggest that dur-
ing the 11-13 gestational weeks a scan, in the mid-sagittal
view of the fetal head, face and brain, certain measurable
abnormalities, such as a smaller palatino-maxillary diam-
eter can raise the suspicion of an underlying CLP [33].
Nevertheless, the diagnosis of orofacial clefts during the
1st trimester of pregnancy has been rarely reported until
now [34-36], but it was recently proved that sagittal color
Doppler ultrasonography can also be useful especially in
the detection of fetal hard palate clefts [37]. Regarding
the soft palate, the absence of ‘the equals sign’ at 2D ul-
trasound was proved to be associated with CLP and is an
indication for supplementary examination of this part of
the palate in a median sagittal section [16].
The finding of an orofacial malformation during the
prenatal ultrasound presents also a major emotional im-
pact on the parents, being a burden for them regarding
both a possible termination of pregnancy (TOP) and their
child’s prognosis after birth [38,39]. Therefore, the ben-
efits of prenatal diagnosis consist also of an adequate pa-
rental counselling involving proper communication skills
[40,41] in order to improve their understanding regarding
the post-natal therapeutic plan and increase their com-
pliance. Even though the prenatal diagnosis of orofacial
clefts was thought to increase the likelihood of TOP [42],
a recent study performed on subjects from Netherlands
proved that most parents did not agree the TOP [39]. It is
also true that health-care providers, especially the obste-
trician and plastic surgeon, were proved to have a great
impact on parents’ decision [39]. TOP was the option in 3
cases in our series, all CLP with soft palate involvement
(2 cases with associated anomalies). However, a multi-
disciplinary team is always required in cases of orofacial
malformation in order to obtain the best outcome.
Conclusions
Prenatal diagnosis of orofacial defects is improving
continuously. CLP, especially the large defects, can be di-
agnosed even at the end of the 1st trimester of pregnancy.
CL is usually diagnosed during the 2nd trimester routine
ultrasound and is commonly an isolated anomaly.
Acknowledgements: This research was partially
supported by the Collective Research Grants of the Uni-
versity of Medicine and Pharmacy Târgu Mureş, Roma-
nia (“The role of mother’s genetic determinism in child’s
Prenatal diagnosis of cleft lip and cleft lip palate
obesity correlated with bioimpedance and anthropomet-
ric parameters” no.275/4/11.01.2017).
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