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Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

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Best Practice & Research Clinical


Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Facial cleft detected: Is the palate normal?


Wassim A. Hassan, MD, Consultant in Obstetrics and Specialist
in Fetal Medicine a, Christoph C. Lees, MD, Consultant in
Obstetrics and Subspecialist in Fetal-Maternal Medicine b, *
a
Fetal Medicine Department, Rosie Hospital, Addenbrooke’s Hospital, Cambridge University Hospitals NHS
Foundation Trust, Cambridge, UK
b
The Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, Du Cane Road, London W12 0HS, UK

Keywords:
Despite advances in ultrasound technology, the sensitivity for
orofacial cleft detection of facial clefts at the routine mid-trimester details scan
palate remains relatively poor. This can be improved by the use of a
alveolar ridge three-point ultrasound screening protocol, although this is not
prenatal routine in many countries. When a facial cleft is suspected at the
ultrasound routine scan, further imaging is usually required to detail the
lip extent of the cleft and presence or absence of any other abnor-
secondary palate
malities. Involvement of the fetal palate is an important finding
detection
that will determine the requirement for surgery, audiology, and
orthodontic services well into teenage years. There remains little
uniformity in how a facial cleft is described antenatally, with
involvement of the alveolar ridge frequently and incorrectly taken
to mean involvement of the palate. Further, midline clefts of the
hard and soft palates, where the fetal lips and alveolar ridge are
intact, are a feature of many genetic conditions, but are almost
never diagnosed by prenatal ultrasound. In this chapter, we detail
issues surrounding the nomenclature of facial clefts in relation to
the palate, and describe some of the more commonly used two-
dimensional and three-dimensional methodologies for imaging
the fetal palate.
Ó 2014 Elsevier Ltd. All rights reserved.

Introduction

Prenatal detection rates for isolated clefts of the lip and alveolus by two-dimensional ultrasound
have historically been poor, ranging from 45–68% [1–3], although a more focused approach using high-
resolution equipment and additional scanning planes (‘face on’; coronal plane through the alveolar

* Corresponding author.
E-mail address: christoph.lees@imperial.nhs.uk (C.C. Lees).

1521-6934/$ – see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bpobgyn.2014.01.010
380 W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

ridge and sagittal profile view) has resulted in an improvement from 34–58% in two consecutive time
epochs through the introduction of the additional scanning planes detailed [4].
One of the most recent papers on cleft detection, from Southern Sweden reflecting contemporary
practice in the period 2006–2010 [5], details a somewhat disappointing detection rate of 31% (43% if
isolated midline clefts are excluded). This detection rate compares unfavourably with a study that most
closely resembles UK practice, based on birth registry data from 2005–2006. This reported a 64% rate of
prenatal detection for cleft lip, palate, or both [6]. It is possible that the detection for facial clefts has
fallen in the UK since the recommendation in January 2010 that the ‘face on’ view only should be
carried out as part of the anomaly scan [7].
Although there is little doubt that the use of higher resolution ultrasound equipment and incor-
poration of protocols for examining the fetal face at the time of the detailed anomaly scan can improve
sensitivity to as high as 75%, the detection rates for clefts of the secondary (hard) palate using two-
dimensional ultrasound have remained low, even in those patients in whom a cleft lip has been
detected. Secondary palatal involvement, however, can alter the long-term prognosis for the child,
being more commonly associated with difficulties in speech, hearing and (after surgery) mid-facial
protrusion. Typically, clefts of the secondary palate require more corrective surgery into teenage
years, and a greater input of audiology, speech and language therapy, and orthodontic intervention. The
accuracy of antenatal diagnosis of facial cleft is, therefore, particularly helpful in preparing parents and
cleft teams for the birth of a child with facial cleft, and for advance planning.
Recent years have seen improvements in two-dimensional imaging and the advent of three- and
four-dimensional ultrasound technology, coupled with different techniques for visualising the fetal face
and, in particular, the hard and soft palates. Little uniformity exists in approach between specialists in
cleft imaging, however, and the many different ways that facial clefts are described. In this chapter, we
consider the confusions in nomenclature associated with facial clefts, and the different techniques and
ultrasound modalities described to assess the fetal palate, particularly where a facial cleft is suspected.

Embryology

Facial clefts result from defective fusion of the facial processes. Clefts of the lip and alveolus occur
because of a failure of fusion of the medial nasal process and maxillary swellings [8]. They may be
unilateral or bilateral, and associated with a cleft of the alveolus on the side of the lip cleft. Clefting of
the secondary (hard) palate has a distinct and different embryological derivation, and is secondary to a
failure of fusion of the two palatine shelves [9].
Clefts of the secondary (hard) palate are, therefore, always midline and posterior to the incisive
foramen and, if they occur together with cleft of the lip and alveolar ridge, they are termed unilateral or
bilateral cleft lip with cleft palate [9,10]. A cleft of the secondary palate where there is also a cleft lip
cannot occur in the absence of cleft of the ipsilateral alveolar ridge except for the rare situation of a
baby suffering from both embryological variants of facial cleft. Facial clefts have been typically divided
into cleft lip with or without palatal involvement. Involvement of the lip and alveolus was said to
represent a cleft of the primary palate, that area anterior to the incisive foramen, with clefts of the
secondary palate being described distinctly. Confusion in terminology means that a child with ‘cleft lip
and palate’ may in fact have a cleft of the primary palate but an intact secondary palate; this represents
a cleft alveolus.
The embryological origins of isolated clefts of the secondary palate seems to be distinct from those
of clefts of the lip and alveolus [8]. The secondary palate comprises the hard palate (immediately
posterior to the incisive foramen) and the soft palate (posterior to the hard palate, containing no bone).
Isolated cleft palate is rarer than unilateral cleft palate or bilateral cleft palate; ultrasound studies
underestimate the incidence of isolated cleft palate, as this condition is rarely diagnosed by prenatal
ultrasound and may even not be identified immediately after delivery.
In Denmark, isolated cleft palate accounts for 25% of the total number of cases of facial clefts [11,12],
but surveys in other countries show that the incidence varies; for example, it is over 50% in Northern
Ireland and Scotland [13–16]. Secondary palate clefts are always midline and result from the failure of
the palatine processes to elevate or grow, so a cleft of the hard palate must also affect the soft palate;
however, it is possible for the soft palate to be cleft with the hard palate.
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Classification of facial clefts

Several classifications for facial cleft exist, most notably those of Kernahan (1958, 1971) [17,18],
Elsahy (1973) [19], and Friedman (1991) [20]. These are all based on postnatal examination, and allow
the key elements of the facial cleft (lip, alveolar ridge, hard and soft palate) to be delineated and, in
addition, the latter two give an indication of the degree of the cleft. The ‘striped Y’ classification
described by Kernahan [18], separately identifies a cleft of the lip, alveolus and (secondary) hard and
soft palate, and allows as much detail as can reasonably expected from prenatal ultrasound scan (Fig. 1).
Confusion may arise in the word isolated: ‘not associated with any other obvious fetal abnormality’
or ‘isolated’ hard/soft palate cleft where this does not affect the fetal lips and alveolar ridge. Therefore,
we reserve the use of the word ‘isolated’ to denote a facial cleft where there is no evidence of any other
abnormality, and use the term ‘midline cleft palate’ to denote a cleft of the palate not affecting the lips.

Epidemiology

Orofacial clefting is one of the most common non-lethal congenital abnormalities and is becoming
more common. The worldwide incidence ranges between 1 and 2.2 per 1000; in Denmark, the

Fig. 1. Description of modified Kernahan ‘striped Y’ schematic.


382 W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

incidence rose from 1.45 per 1000 live births in 1942 to 1.89 per 1000 in 1981. Birth registry data from
Denmark and Finland suggest an incidence in livebirths of 1.69 and 1.74 per 1000, respectively [21–24].

Syndromic associations with facial clefts

A genetic or chromosomal contribution to facial clefts has been described in many syndromic as-
sociations. A number of genes has been identified and known to play a role in the craniofacial
development (1p36, 2p21, 3p11.1, 8q21.3, cleft lip and palate transmembrane protein 1, GAD1, AXIN2,
FGFR1, FGFR2, IRF6, PDGFC etc) [22–24]. Although many clefts run in families, in a large number of
cases there is no corresponding syndromic appearance yet identified. Moreover, our knowledge about
the genetic factors that contribute to the more common cases is still incomplete. In Table 1, we detail
some of the syndromic associations and their type of inheritance in relation to facial clefts.

Two-dimensional techniques for visualising the hard palate

Septo-lingual view

We have described 11 cases where it was possible to diagnose prenatal cleft palate on two-
dimensional ultrasound. Cases were considered to have a cleft in the hard palate if the tongue was
seen moving next to or abutting the nasal septum in transverse view (Fig. 2a and b). All cases also had
three-dimensional reverse rendering technique. In 11 women referred with a possible diagnosis of
facial cleft, the technique yielded a positive result. In these cases, there was complete concordance with
three-dimensional reverse face views and postnatal follow up. Visualising the tongue abutting the
nasal septum in the transverse view indicates strongly the presence of the cleft in the hard palate, as
the tongue would not otherwise be visualised in the same plane as the septum. As the tongue may
appear indistinct in a frozen image, the technique can only be considered to give a positive result if the
tongue is seen moving next to the nasal septum in the transverse view. Two-dimensional ultrasound
may be a useful additional modality in the diagnosis of hard palate cleft. We do not yet have sufficient
cases where the technique gave a negative result to determine its value in excluding cleft of hard palate.

Table 1
Genetic and chromosomal associations with cleft lip and palate.

Syndrome Cleft lip and palate Inheritance Genetic or Incidence


chromosomal basis
Trisomy 13 Bilateral cleft lip and palate Sporadic or translocation 47 XX or 47 XY þ13
Trisomy 18 Unilateral or bilateral cleft lip Sporadic or translocation 47 XX or 47 XY þ18
with or without alveolar ridge
or palate
Triploidy Bilateral cleft lip and palate or Sporadic XXX, XXY, XYY
complete absence of midline
facial structures
Goldenhar Lip and palate Sporadic 1 in 5000
Treacher–Collins Palate Autosomal dominant 1 in 50 000
syndrome
Sticklers Palate and bifid uvula Autosomal dominant 1 in 7500
Pierre–Robin Palate Sporadic 1 in 10 000
DiGeorge Palate Autosomal dominant 22q deletion 1 in 3000
Meckel–Gruber Palate Autosomal recessive 1 in 20 000
Nager Palate with or without lip Sporadic 1 in 50 000
Gorlin Lip, alveolar ridge and palate Autosomal dominant 1 in 100 000
Hydrolethalus Lip, alveolar ridge and palate Autosomal recessive 1 in 20 000
Oral–facial-digital Lip, alveolar ridge and palate X-linked dominant 1 in 100 000
type I
Oral–facial-digital Lip, alveolar ridge and palate Autosomal recessive Not known
type II
Van der Woude Lip, alveolar ridge and palate Autosomal dominant 1 in 75 000
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Fig. 2. (a) Transverse ultrasound view of the fetal face at the level of the nasal septum showing a deviated nasal septum with the tip
of the tongue abutting the nasal septum; (b) coronal representation of the fetal face and nasal septum showing in the left image the
normal relationship between the hard palate, nasal septum and tongue. On the right is shown a gap in the hard palate with tongue
protruding into the ethmoid sinus adjacent to the nasal septum Published with permission from Mr Jeffrey Brain, FRCS.

Two-dimensional techniques for visualising the soft palate and uvula

Recently Wilhelm and Borgers [25] suggested the use of a novel marker for diagnosing isolated cleft
palate with the sonographic appearance of an ‘equals sign’. A total of 667 consecutive women between
20 and 25 weeks gestation were referred for a detailed anomaly scan. The uvula was visualised by frontal
section through the neck and pharyngeal space, and the epiglottis served as the landmark for identifying
the uvula. A normal uvula resembled an equals sign (two hyperechogenic lines with hypoechoic in-
termediate space). Also the uvula could be visualised in a transverse section through the head at the level
of the thalamus; the transducer was moved parallel to this plane in the caudal direction until the
nasopharynx was visualised in the centre; further movements of the transducer enabled the soft palate
and uvula to be identified. A typical ‘equals sign’ could be visualised in 90% of cases (605 out of 667) and
the soft palate in median sagittal section in 85% of cases (569 out of 667). Detection of either the uvula or
384 W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

the soft palate was successful in 98% of cases (656 and 667). Three cases with clefts were diagnosed. In
one case, neither the uvula nor the soft palate could be visualised by ultrasound; in another case of
unilateral cleft, this method confirmed the involvement of the soft palate and a complete cleft uvula. In a
third case of bilateral cleft, this method correctly diagnosed continuous cleft of the soft palate. A sig-
nificant training effect was observed during the study; the examination time required for making
appropriate adjustments significantly decreased over time, and the ability to interpret ultrasound
findings made in poor conditions increased significantly. The method could be used as a routine two-
dimensional ultrasound screening examination of the soft palate.

Three-dimensional techniques for visualizing the hard palate

In the past decade, three-dimensional ultrasound began to play an important detecting role in the
evaluation of craniofacial anomalies. It has proved to be more effective in visualising the palate and
palate defects. In this section, we describe some of the more commonly cited three-dimensional
techniques used for visualising the hard palate.
Whether or not three-dimensional imaging represents a genuine advance in cleft imaging remains
open to debate. In a series of craniofacial anomalies, Ghi et al., in 2002, compared the effectiveness of
two- and three-dimensional ultrasound in the accuracy of diagnosis [26]. Thirty-seven cases before 24
weeks gestation with clefts (lip and palate) were analysed retrospectively. Two-dimensional evaluation
of the fetuses included multiple sections of the fetal face and cranium to demonstrate the eyes, nose,
lips and the alveolar ridge of the palate and the mandible. Coronal, axial views, and a profile view of the
face were obtained. Three-dimensional acquisitions were captured and rearranged in a computer
workstation and then processed for surface rendering to provide a realistic representation of the fetal
face and the palate. Two-dimensional ultrasound easily and rapidly recognised and categorised facial
clefts in all cases using a combination of coronal and axial views. Cleft lip was always best visualised in
an anterior coronal plane; however, when the defect was extended to the palate, an axial view of the
maxilla proved better (Fig. 3). Three-dimensional ultrasound confirmed the diagnosis in 11 out of 12
fetuses; however, they reported time-consuming methods (30 mins) with three-dimensional ultra-
sound was compared with two-dimensional ultrasound when the examination was carried out in a few
minutes. Two-dimensional ultrasound in expert hands allows an accurate diagnosis of craniofacial
abnormalities from early gestation, and that three-dimensional ultrasound did not add any valuable
diagnostic information.

Reverse face view

Campbell and Lees in 2003 described a novel technique ‘three-dimensional reverse face’ for
visualising the palate [27]. Using a four-dimensional slow frame rate (2.7 Hz) image or a three-

Fig. 3. Unilateral cleft lip and palate; (a) the coronal view shows the cleft lip with distortion of the nasal tip and asymmetry of the
nostrils; (b) the axial scan through the fetal maxilla (b); (c and d) the cleft extending to the alveolar ridge. Three-dimensional
sonogram with surface rendering in the same case. Published with permission UOG.
W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389 385

Fig. 4. Three-dimensional ultrasound image (frontal view) of the affected fetus showing the bilateral cleft lip. Published with
permission UOG.

Fig. 5. Face view to allow visualisation of the lips, and then the viewbar is scrolled through the lips until the alveolar ridge is identified.
Published with permission UOG.
386 W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

Fig. 6. The alveolar ridge and palate using the reverse face view. Clear visualisation of the orbits, nasal cavity with septum and palate
are identified at all levels from the alveolus (a) to the posterior aspect of (b–d) the hard palate. Published with permission UOG.

dimensional sweep, the viewbar was adjusted to provide an optimised surface-rendered image of the
face (Fig. 4). The face was adjusted in a frontal view to allow visualisation of the lips, and then the
viewbar is scrolled through the lips until the alveolar ridge is identified (Fig. 5). A return to the
frontal view of the face was made, and the face rotated through 180 . This provides an unobstructed
W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389 387

view of the palatal area, nasal cavity, and orbits. The viewbar is then scrolled through the length of
the palate (Fig. 6a–d). The same group in 2005 evaluated this technique in eight cases, and found that
the visualisation of the palate is feasible and rapid, taking only 2–3 mins [28]. Optimal visualisation
of the hard palate was obtained by surface-rendered mode; the appearance of a limb in front the face
may cause significant shadowing; however, the views were not affected by the umbilical cord or the
placenta. A larger study, including over 100 patients using three-dimensional imaging as an adjunct
to two-dimensional imaging, showed that the accuracy of diagnosis of most types of cleft was over
90% [29]. In this study, only one baby was subsequently found to have an undiagnosed genetic
condition.

Flipped face view

Subsequently, Platt et al. [30] suggested the ‘flipped face’ technique for assessing the hard and soft
palates. Using three-dimensional static volume of the fetal face with the fetus in supine position, 90
rotation of the acquisition is carried out so that the cut plane was directed in a plan from the chin to the
nose. The viewbar is then scrolled from chin to nose to examine the lower lip, mandible and alveolar
ridge, then the tongue, upper lip, maxilla, alveolar ridge and hard and soft palates. The authors of this
study suggested this technique could provide full description of the fetal palates and face; however,
they reported a major limitation. The technique requires the acquisition of an adequate facial volume
that does not have shadowing of the palate, which could be misinterpreted as a defect. In addition, if
the fetal face is directed posterior, this technique cannot be used because of shadowing from the oc-
cipital bones of the skull.

Angled insonation

Pilu et al. [31], in 2007, described a new technique for the visualisation of the secondary palate using
three-dimensional ultrasound. Fifteen normal fetuses between 19 and 28 weeks gestation, and one
fetus with cleft lip and palate at 33 weeks gestation, were studied. This method suggested obtaining an
image of the face, aligning the probe with the profile of the fetus. To avoid shadowing from the alveolar
ridge, Pilu et al. [31] used an angled approach by insonating the secondary palate at an angle of about
45 (Fig. 1). Static ultrasound volumes were obtained and analysed offline using multiplanar, surface
mode, static volume contrast imaging, and tomographic ultrasound imaging. Good-quality volumes
were possible in 10 of the 15 normal fetuses, and in the fetus with cleft lip and palate. Unfavourable
position of the fetus and fluid in the oral cavity were the main disadvantages of the technique, whereas
better results were obtained when the fetus was facing the transducer and the head was slightly
extended.

Three-dimensional techniques for visualising the soft palate and uvula

A first-trimester method for evaluating the anatomy of the palate and the ‘retronasal triangle’ has
been described by Sepulveda et al. [32] One hundred consecutive normal fetuses at the time of
routine two-dimensional first-trimester screening (11–13 þ 6 weeks) had the retronasal triangle
identified as the three echogenic lines formed by two frontal processes of the maxilla and the palate
visualised in a coronal view of the fetal face posterior to the nose. In a separate study of five fetuses
confirmed postnatally with cleft of the palate, three-dimensional ultrasound images, including
multiplanar views, were analysed. Abnormal appearance of the retronasal triangle was identified in
all five cases with cleft of the palate. The group suggested incorporating the ‘retronasal triangle’ in
first-trimester screening in view of the feasibility of obtaining clear anatomy of the palate by two-
dimensional ultrasound.

Conclusion

With the use of modern ultrasound techniques and the ability to define facial clefts according to a
systematic classification, it should be possible both to image and describe facial clefts prenatally with a
388 W.A. Hassan, C.C. Lees / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 379–389

high degree of accuracy. This includes defining hard palate involvement by targeted systematic two-,
three-dimensional ultrasound examination, or both, in over 90% of cases where there is a cleft in the
fetal lips, alveolar ridge, or both.
A greater challenge is in identifying isolated clefts of the hard and soft palate, where there is no
cleft of the fetal lips to alert the ultra-sonographer to look in more detail at the fetal face. Screening
for isolated hard and soft palate cleft is unlikely to be realistic in routine practice. Targeted assess-
ment, however, of the fetal palate in the context of either a family history of hard and soft palate
clefts (e.g. in Stickler Syndrome), or where there is another fetal abnormality, is realistic, although the
sensitivity for diagnosis of midline facial cleft in the absence of any other ultrasound markers may be
low.

Practice points

 In routine ultrasound screening using a three-point multiplanar technique, 65% or more of


facial clefts can be identified at the mid-trimester scan.
 Where cleft lip, alveolar ridge, or both, is detected, careful two-dimensional ultrasound,
supplemented with three-dimensional ultrasound can in over 90% of cases detect a cleft of
the hard palate.
 Midline cleft palate, where the fetal lips are normal, is almost never diagnosed prenatally
unless there is suspicion from family history, and expert ultrasound is carried out specifically
looking for a defect in the hard and soft palates.
 Where facial cleft is identified in the presence of low-risk trisomy screening, and detailed
ultrasound discloses no other abnormality, the risk of an underlying genetic or chromosomal
condition is less than 2%.

Conflict of interest

None declared.

Acknowledgements

Christoph Lees is supported by the National Institute for Health Research (NIHR) Biomedical
Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The
views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the
Department of Health.

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