Normal and Abnormal Fetal Face Atlas 2017

Normal and
Abnormal
Fetal Face Atlas
Ultrasonographic Features
Jean-Marc Levaillant
Jean-Philippe Bault
Bernard Benoit
Gérard Couly
123
Normal and Abnormal Fetal Face Atlas
https://www.facebook.com/groups/2202763316616203
Jean-Marc Levaillant
Jean-Philippe Bault • Bernard Benoit
Gérard Couly
Normal and Abnormal

Fetal Face Atlas
Ultrasonographic Features
Jean-Marc Levaillant Bernard Benoit
Center of women and fetal imaging Princess Grace Hospital
Créteil Monaco
France
Gérard Couly
Jean-Philippe Bault Department of maxillo-facial surgery
Center of fetal imaging Ambroise Paré Necker Hospital
Les Mureaux Paris
France France
Translation from the French language edition ‘La face foetale normale et pathologique:
aspects échographiques’ by Jean-Marc Levaillant, Jean Philippe Bault, Bernard
Benoit, Gérard Couly © Sauramps Médical, Paris, 2013; ISBN: 978-2840238690
ISBN 978-3-319-43768-2 ISBN 978-3-319-43769-9 (eBook)

DOI 10.1007/978-3-319-43769-9
Library of Congress Control Number: 2017933711
© Springer International Publishing Switzerland 2017

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Foreword
In the field of obstetrics and fetal medicine, there are a few invariables in
clinical use of ultrasounds. The operator must have a clear representation of
the structures he or she is analyzing and the possible anomalies, which sup-
poses knowledge of basic physiology, anatomy, and embryology. He or she
must be able to use the spectrum of technical solutions available, know what
to expect from them, and use them in the most up-to-date fashion, such as not
generating images that are aesthetically pleasing but lack information. He or
she should take a systematic approach, standardizing imaging via an analysis
through the planes of symmetry; the idea is to be able to reproduce the exami-
nation and to avoid creating nice-looking but fallacious images. When it is
pertinent, use of objective quantitative criteria should be privileged.
Communication should also be taken into consideration—a communica-
tion based on transmitting information rather than producing flashy images.
It is important to understand the expectations of the various partners
involved—geneticists, pediatricians, surgeons, and parents—and be able to
respond to their specific questions.
Sharing experience is an important part of our practice. Teaching involves
disseminating knowledge and showing targeted images; it also involves trans-
mitting how to obtain these images via a multitude of approaches: words,
screen captures, hands-on tutoring, and live demonstrations.
This list must also include (self-) assessment, which is at the heart of any
responsible practice.
This atlas of normal and abnormal fetal face ultrasound imagery presented
by Jean-Marc Levaillant, Jean-Philippe Bault, Bernard Benoit, and Gérard
Couly fits this approach. It provides a clear, didactic approach with a review
of the basic embryology and anatomy needed to understand the images, along
with up-to-date clinical knowledge and the links between clinical practice
and the images under both normal and various pathological situations. It also
includes a collection of biometric curves. Beyond the images themselves,
readers will appreciate the authors’ explanations of the optimization and uti-
lization of the various ultrasound imagery modes, as well as how to obtain the
various shots and corresponding images.
In this respect, this atlas is another step in the development of the French
School of Gynecological and Obstetrical Ultrasonography, which includes
some major developments, including pioneering developments in 3D ultraso-
nography in collaboration with Philips Research Laboratories, followed by
the first industrial developments with KretzTechnic; training in 2D and 3D
v
vi Foreword
ultrasound imagery at the Saint-Denis Ultrasound School, with trainers from

all over France and let by the tireless and ubiquitous applied engineer Bernard
Meyer; and journal publications on fetal face ultrasound imagery.
Daniel Rotten
Department of Gynecology and Obstetric
Delafontaine Hospital
Saint-Denis
France
Acknowledgements
We would like to thank our colleagues who contributed to the imagery found
in this atlas:
Caroline Alby
Bettna Bessières
Christian Bisch
Joseph Bonan
Rabi Chaoui
Sophie Couderc
Laurent Guibaud
Soraya Kabar
Brigitte Leroy
Anne Elodie Millischer
Daniel Moeglin
Marc Molho
Edwin Quarello
Ahmed Sadji
Karima Sedikhi
vii
Contents
1 Introduction Craniofacial Epigenesis in Vertebrates �� 1

1.1 The Key Stages in Craniofacial Development�� 1
1.1.1 Cell Death �� 8
1.1.2 Genetic Determinants and Differentiation of Intra-
prominence Cellular Phenotypes�� 8
1.2 Cellular Phenotypes Originating from the Neural Crest�� 8
1.3 Summary �� 15
2 Normal Face�� 17
2.1 What Is Included in a Basic Sonographic Survey
and a Diagnostic Sonographic Survey?�� 18
2.2 Routine Trimester Examinations�� 19
2.2.1 First Trimester�� 19
2.2.2 The Second and Third Trimesters�� 23
2.2.3 Spotlight on the Third Trimester�� 28
2.3 Biometrics of the Face�� 36
2.3.1 Thickness of the Forehead Skin�� 36
2.3.2 Length of Philtrum�� 38
2.3.3 The Nasal Bones �� 39
2.4 Facial Angles�� 40
2.4.1 Upper Facial Angle �� 40
2.4.2 Lower Facial Angle�� 41
2.4.3 Measurements of the Inter-orbital Distance�� 42
2.4.4 Measurements and Views of the Mandibular
and Maxillary Width �� 44
2.5 Practical Review Work�� 50
3 Clefts and Pierre-Robin Syndrome�� 57
3.1 Clefts �� 57
3.1.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
3.1.2 Symptomatic Analysis of Clefts . . . . . . . . . . . . . . . . . . 58
3.1.3 Ultrasound Diagnosis of Clefts: Analytical Study. . . . . 60
3.1.4 Cleft Algorithm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.1.5 Ultrasound Diagnosis of Labioalveolar-Palatal
Clefts: Summary �� 70
3.1.6 The Decision-Making Process After the Discovery
of a Facial Cleft�� 72
ix
x Contents
3.2 Pierre-Robin Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

3.2.1 How to Screen for Retrognathia. . . . . . . . . . . . . . . . . 73
3.2.2 What to Look for in Cases of Retrognathia. . . . . . . . . 76
4 Dysmorphism�� 79
4.1 How to Define Objective Facial Dysmorphism�� 79
4.2 Tools for This Study�� 79
4.3 Dysmorphism of Major Chromosomal Anomalies�� 79
4.3.1 Trisomy 21�� 79
4.3.2 Trisomy 18�� 85
4.3.3 Trisomy 13�� 87
4.4 Upper Face Pathologies�� 95
4.4.1 Wolf-Hirschhorn Syndrome�� 95
4.4.2 Craniostenosis �� 95
4.5 Mid-Face Pathologies �� 107
4.5.1 Achondroplasia �� 107
4.5.2 Maxillo-Facial Dysplasia: Binder Syndrome�� 112
4.5.3 Thanatophoric Dysplasia�� 117
4.5.4 Prader-Willi Syndrome �� 120
4.5.5 Otopalatodigital Syndrome �� 122
4.6 Lower Face Pathologies�� 123
4.6.1 Otomandibular Dysplasias�� 123
4.6.2 Beckwith-Wiedemann Syndrome �� 131
4.6.3 Fetal Alcohol Syndrome �� 135
4.7 Multiple-Level Pathologies�� 138
4.7.1 Cornelia de Lange Syndrome�� 138
4.7.2 Williams-Beuren Syndrome�� 144
4.8 A Few Additional Syndromes�� 147
4.8.1 CHARGE Association�� 147
4.8.2 Noonan Syndrome�� 154
References�� 158
5 Facial Tumors �� 163
5.1 Teratomas�� 163
5.2 Hemangiomas �� 166
5.3 Lymphangiomas�� 168
5.4 Expansive Process of Brain Tumors �� 171
5.5 Pai Syndrome�� 173
6 The Eye �� 175
6.1 Embryology Review�� 175
6.1.1 Ultrasound of a Normal Eye �� 175
6.1.2 Main Aspects of Ocular Pathologies�� 182
7 Biometric Parameters�� 199
7.1 The Eyes�� 199
7.2 The Lens�� 203
7.3 Vitreous Circumference�� 203
7.4 Ocular Diameter�� 205
Contents xi
7.5 Lens Circumference�� 205

7.6 The Ear�� 206
7.7 Nasal Bones�� 210
7.8 Nose Width �� 210
7.9 Nostrils�� 211
7.10 Maxillary Bone Length �� 212
7.11 Alveaolar Ridge Width �� 213
7.12 Tongue�� 213
7.12.1 Skin Thickness Facing the Forehead�� 214
7.13 Length of Philtrum�� 215
7.14 The Ears�� 216
7.15 Lower Facial Angle�� 217
7.16 Upper Facial Angle �� 218
7.17 Maxillary Width�� 219
7.18 Mandibular Width �� 220
7.19 IOD �� 221
Introduction Craniofacial
Epigenesis in Vertebrates 1
The facial bones, as they appear in a fetal 1.1 he Key Stages

T
ultrasound image, result from a continuous
in Craniofacial Development
process of development, regulated and

sequenced by genetic and molecular embryol- The prescribed regions of the face and brain are
ogy, which progressively constructs the face differentiated as early as the gastrula and neu-
like epigenesis. rula stages.
The face, like the entire head, is “prefigured” Gastrulation lays out the embryonic body
by prescribed regions that are genetically deter- plan for all vertebrates with bilateral symmetry
mined during the gastrula and neurula stages. Via via the formation of the notochord and the meso-
typological deformations, the two-dimensional derm interposed between the endoderm and the
neural surface transforms symmetrically and ectoderm (Fig. 1.1) (this beginning explanation
acquires a third dimension. of epigenesis or the phenomenology of develop-
When the dorsal region of the neural grove ment by stages replaced the eighteenth century
closes into a tube, the “fourth layer” of migrating concept of preformation that stemmed from the
neural crest cells invade the future embryonic building of the first microscope, when
cephalic pole and provide the cellular filling for Leeuwenhoek, its inventor, identified the sperma-
the facial prominences. tozoid in 1677).
The face develops thanks to the five founding The future regions of the face are situated in
prominences or swellings of the ectoderm, which the rostral regions of the gastrula.
grow volumetrically and then fuse by contact and Neurulation is a theater of morphogenetic
are no longer recognizable as having existed once operations that will differentiate the prescribed
the face is totally formed. These prominences are: regions of the head (Fig. 1.2). This is the stage
during which the central nervous system, the
• The frontonasal prominence, which is median, facial mass and the neck truly begin their
single, symmetrical and different from the morphogenesis.
other four as it is formed by two left and right The neural plate is the two-dimensional cel-
halves. lular surface whose fate mapping demonstrates
• The maxillary prominences, right and left. the closeness and unity of the regions of the
• The mandibular prominences, right and left brain, the neuro-sensorial receptors, and the face,
(first branchial arches). genetically “printed” on the neural plate.
© Springer International Publishing Switzerland 2017 1

J.-M. Levaillant et al., Normal and Abnormal Fetal Face Atlas, DOI 10.1007/978-3-319-43769-9_1
2 1 Introduction Craniofacial Epigenesis in Vertebrates
Nicolas Hartsoeker’
Caspar F. Wolff’s epigenesis, 1759:
homunculi, 1694: the
human fetus develops in development via successive stages with
full in the spermatozoid. layers having different roles
Neural crest
Ectoderm
Neural plate
Mesoderm
Notochord
Endoderm
1 Vertebrate embryo in early neurula stage.
Fig. 1.1 Preformationism vs. epigenesis. 1 Homunculus. 2 End of gastrula phase, beginning of neurula stage
During neurulation, the topological trans- under the diencephalon and thus becomes the
formation of the neural plate continues. The posterior-most region, above the future stomo-
face is in the neurula and “grows” in front of it deum. The two olfactory placodes sprout
(Fig. 1.3). nerves and the olfactory apparatus, initially
The neural plate lengthens and folds, forming located above and on either side of the telen-
a groove with edges rising up and fusing into a cephalon and the adenohypophysis, approach
tube (Figs. 1.4 and 1.5). the median line due to the median fusing of the
Closure of the neural tube’s rostral opening neural ridges and position themselves ventrally
represents an exceptional topological originality under the tele-dicephalon, or the anterior brain
(Fig. 1.6): the anterior-most parts of the neural (Fig. 1.10).
plate roll up forward, completing a half-circle This is how the future nasal cavities and the
rotation (180°), flipping these regions into a ven- rhinencephalon are linked for the sense of smell.
tral position (it is an elegant and original solution Jointly, the retina surfaces on the neural plate
to the problem of closing a tube that is open in “blister” outwards and becomes the optic cups
the front (Figs. 1.7 and 1.8). and then the optic vesicles (see Fig. 1.7).
The lateral edges of the neural tube come The dorsal closure of the neural tube by
together and fuse in the middle. As a result, the molecular fusion triggers the migration of
adenohypophysis (Fig. 1.9), initially the cephalic neural crest cells (CNCC) (see
anterior-most neuro-ectodermic region, moves Figs. 1.4, 1.11, 1.12, 1.13, 1.14 and 1.15).
1.1 The Key Stages in Craniofacial Development 3
Hypothalamus
Neural Plate Adenohypophysis
Nasal cavity
Olfactory
Placode
PROSENCEPHALON
Naso-frontal ectoderm
Telencephalon
Eye
Posthypophysis
Optic placode
Thalamus
Epiphysis
Maxillo-mandibulary
Trigeminal placode
MESENCEPHALON
ectoderm +
COULY and LE DOUARIN
Dev.Biol.120-198-214 (1987)
Mesencephalon
Trigeminal
placode
nc
nc nc
nc
Nc: neural crest
Fig. 1.2 Map of neural plate regions
Ah
NC
Fig. 1.3 The face grows in front of the neural plate

Neural plate Dorsal fusion
Nc
Nc
Neural tube
Nc: Neural crest

D 15 D 18
Fig. 1.4 Closure of the neural plate into the neural tube, with neural crest
D 15 – The neural plate
D 18 – Dorsal fusion
NC Neural crest
Neural tube
Frontal view
Fronto-lateral view
Mouse, D8-D8,5; human, around D22
Fig. 1.5 Topogenesis of the anterior neural plate and beginning of the optic cup.
The optic cups invaginate. Elevated neural ridges move closer together on the dorsal side of the embryo
Frontal view
Fronto-lateral view
Mouse, D8-D8, 5; human, around D22
D 2O
Rotation
Cerebral
A
Facial
D 30
Expansion
D 40
Ventralization
Fig. 1.6 Overall ventral rotational movement of the rostral extremity of the embryo
1. Rotation–D20
2. Facial cerebral expansion – D30
3. Ventralization – D 40
the optical pits,

the ectoderm and
the mesenchyme.
anterieur posterieur
Mouse D 8,5; human around D 22-24
Fig. 1.7 Optical vesicles and the median closure of the rostral extremity
In this cut, one can observe the links between:
The optical buds, the ectoderm and the mesenchyme
Anterior
Posterior
Mouse D8, 5; Human around D22-24
Neurula: at 22 days
Lateral view View from above
Fig. 1.8 Scanning microscope images of anterior neural topology

Neurula: Day 22
Lateral view
View from above
As the neural tube lengthens and rolls over the olfactory placodes and the branchial placodes.
180° to achieve rostral and median closure, At this stage, the right and left olfactory placodes
CCNC migrate dorso-ventrally, leaving the cen- attract neural crest cells as a result of the expres-
tral nervous system and invading the cranial sion of mitogenetic molecules, growth factors
extremity of the embryo, between the ectoderm such as FGF 8, transcription proteins, and the
and the endoderm. DLX5, SLX6 and SHH genes, which are
This very particular strategy determines the strongly expressed in these placodes.
cellular volume of facial morphogenesis. The CNCC amass around these placodes, and
Thanks to their serious mitotic capacities, thanks to their mitoses, ensure the development
these cells will collect around the optic vesicles, of the five prominences of the future face:
Adenohypophyse
Fig. 1.9 Rostral neural topogenesis and final position of the adenohypophysis
The rostral dorso-ventral rotation outlining the pituitary gland in vertebrate embryo
*
*
Fig. 1.10 Human neurula at 27 days (Dr. C. Nilsson)

Telencephalon and olfactory placodes (*)
• The frontonasal prominence, which is median, The fusion of the two internal nasal pits char-
single, symmetrical and different from the other acterizes the median neural symmetry. This
four as it is formed by two left and right halves. fusion with the two maxillary prominences is
• The maxillary prominences, right and left. only possible by way of embryonic cell death or
• The mandibular prominences, right and left apoptosis. This cell death implies the existence of
(first branchial arches). molecular signals such as collagenase, caspase,
protease, metalloprotease, and folic acid. For
now, it is not entirely understood.
1.1.1 Cell Death
The fusion of the five face prominences after they 1.1.2 Genetic Determinants
come into contact with each other is only possi- and Differentiation of Intra-
ble because of embryonic cell death, or apopto- prominence Cellular
sis. This paradoxical developmental phenomenon Phenotypes
was not recognized as fundamental at the time of
its discovery in the 1960s (Gluckmann), but later In the end, each facial prominence is character-
became viewed as a process required for ized by its own genetic personality thanks to the
balancing out cell proliferation during the devel- expression of genes whose effects are repre-
opment of all living beings. sented by cellular proliferation and differentia-
As an originator example, cellular death or tion that ultimately develops into organs (bone,
morphogenetic necrosis of interdigital webbing cartilage, muscles, teeth, dermis, nerves, vessels,
contributes to separating the fingers and toes from etc.). Each prominence is thus responsible for
each other. The first genes commanding cell death the specific tri-dimensional construction of a
generate internal processes in each concerned specific skeletal and tissue territory of the facial
cell, triggering a suicide, or cell sacrifice. These mass, and of its anatomic and functional
genes began to be identified in the early 1980s. organization.
In every living cell, there exists a genetic If a development gene is defective in a promi-
death program, which when activated causes the nence, the latter cannot undergo satisfactory mor-
cell to implode and disappear (this differs from phogenesis, which then impacts it final qualitative
cells that necrotize by explosion, trauma, or viral and/or quantitative development, by notably dis-
infection because they are surrounded by blood turbing the fusion of this prominence with the
cells such as macrophages). adjacent ones, resulting in the various morphoge-
Cell death by apoptosis is quick, does not lead netic accidents that can be observed, such as
to inflammation, lesions, or scarring, which is clefts, hypoplasia, inclusion of embryonic relics,
why it went unnoticed for so long. fistulas, and ectodermic cysts. Yet, these accidents
The first genes found to trigger cell death were will always conserve a developmental logic as
CED-3 and CED-4 (Horwitz). Another identified well as facial and oral topographic coherence.
gene—CED-9—antagonizes and represses these
genes and their effects.
From the most primitive creatures, such as 1.2 Cellular Phenotypes
worms, through to mankind, these genes have Originating from the Neural
remained functional, representing the same Crest (Fig. 1.15)
molecular process for millions of years. This sys-
tem of cellular death and survival were preserved Classification of the normal and dysmorphic
intact. The molecular trigger for cell suicide is face (Fig. 1.16) — The six potential clefts
linked to the activity of protease and caspase. around the mouth (Fig. 1.17).
Cell death or apoptosis is essential to the Taking into account this genetic embryology,
formation of all facial anlage: of the double which leads to the modular construction of the
symmetry of the upper lip and of the fusion of face, it is possible to propose a modular topo-
the basic face prominences. graphical classification of facial and cervical
1.2 Cellular Phenotypes Originating from the Neural Crest 9
This human embryo, whose cephalic

extremity we see here, is
over 30 days old. We
have represented
the various ridges
of the face: their
volume develops
from the migration
of neural crest cells
(purple arrows). At this
stage, the future head is
resting on the heart. The
placodes (optical, otic and
1’arc olfactory), each consisting of
an ectoblastic layer of cells, are
2’arc the future sense organs.
3’arc
4’arc
Fig. 1.11 Neural crest cells migrating and the development of facial prominences
Posterior CNC
CNC
Anterior CNC
CNC
CNC
Fig. 1.12 Embryonic microsurgery documenting the migration of NC cells

Migration of cephalic neural crest cells (CNC)
Anterior CNC
CNC
Posterior CNC
Fig. 1.13 Development of face prominences

D31-36
Fig. 1.14 Human embryo face at around day 42 Neural

crest cells
- Facial and cranial osteo-cartilaginous skeleton

- Sclera, choroid and anterior segment of the
eye facial dermis, meninges
Cephalic level - Vascular walls of facial and cerebral vessels
NC without Hox
genes - Odontoblasts
- Tendons and muscular connective tissue
- Glial cells (Schwann)

- Glandular support cells
- Pigmentary cells
- Nerve cells
- Bipolar neuroblasts (medullar ganglions and
Cervical-body cranial nerves)
level
NC expressing
Hox genes - Multipolar neuroblasts of the autonomic
nervous system
- Endocrine cells
-calcitonin
-carotid body
-medulloadrenal
Fig. 1.15 Cellular phenotypes originating from the neural crest

2 Mnf 3
Mmx Mmx
4 5
Mmd Mmd
6
arch 1
arch 2
2 3
arch 3
NECK
arch 4
1
Fig. 1.16 Meridian and modular classification of morphological cephalic accidents
malformations and, as a result, provide keys for A total or partial defect in the median fusion of
understanding them. these two halves impacts the future nasofrontal
The median neural symmetry of the face prominence, which will present the frequent median
results from the rostral closure of the neural defects—partial or total schism, encephalocele, fis-
tube (Fig. 1.18). tula, cyst, etc.—that are observable with ultrasound.
The frontal, single and median, prominence This median facial cleft never extends beyond
develops by the fusion of two halves, right and left, the adenohypophysis and the sella turcica.
resulting from an original neural symmetry, the for- Embryology is a powerful predictive engine that
mation of which implies a process of fusion by is never at fault.
molecular “median adhesion” by N.CAM (neural The maxillary and mandibular prominences
cell adhesive molecule) dependent on the expres- have their own dysmorphisms, including intra-
sion of genes of the neural groove surface prominence clefts and hypoplasias. (PL 1.19
epithelium. and 1.20).
1 2
Fig. 1.17 The 6 clefts around the mouth
1 2 3 4 5
6 7 8 9 10 11
12 13 14 15 16
Fig. 1.18 Malformations of the nasofrontal-premaxillary external orbital. 11,12: hemi-arrhinia. 13: nasal proboscis.
prominence. From 1 to 9: median clefts and frontonasal 14: cyclopia. 15: nostril duplication. 16: arrhinia
encephaloceles. 10: bilateral labio-maxillary clefts and (ultrasound)
2 3 4 5 6
7 8 9 10 11
Fig. 1.19 Malformations of the maxillary prominences. velopalatine clefts. 6, 7: Goldenhar syndrome. 8, 9.:
2: aprosopia of the maxillary prominence. 3, 4: uni- and Franceschetti syndromes. 10, 11: homeotic duplication of
bilateral colobomas. 5: labio-maxillary and bilateral the maxillary prominence
2 3 4 5
6 7 8
10
10
11 13 14
Fig. 1.20 Malformations of the mandibular prominences. 2, 3: otocephalia. 4, 5, 6, 7, 8: First arch syndrome with
macrostomia. 9, 10: fossa and fibrochondroma of the chin. 11, 12: homeotic duplication of the mandible
1.3 Summary 15
1.3 Summary Defects in all or part of these molecular strate-

gies in one or more of the facial prominences
The final morphology of the fetal face results leads to the development of morphological
from a succession of stages punctuated by molec- accidents.
ular signaling whose visible effects are The facial mass and the brain and the skull,
successively topological deformations, cellular
which make up the head, are inseparable as they
migrations, numerous cellular death or apoptosis, both belong to the same neural compartment.
and then acquisition of cell phenotypes. (Figs. 1.21 and 1.22).
SNF
P
TC
III
SMM IV
V
VI
VII
VIII
XII
IX
X
XI
Fig. 1.21 Malformations associated with the face and the brain
Fig. 1.22 Facial skeleton (in grey) is made up of neural crest cells
Normal Face
2
The ultrasound of the face is perhaps the most pediatrician who first of all examines a newborn’s
important moment in the examination of the fetus face, this view provides much information about
with regards to the impact for the parents who potential pathologies. The same applies to the
have come to “see their baby.” fetus, and yet, strangely, the “minimum” recom-
This exam procures both anxiety about the mended exam minimalizes the examination of
potential discovery of a malformation and pleasure the face.
in seeing their future child on the ultrasound screen. The chapters that follow will provide proof of
This exam is also very important for the ultra- the importance of this exam.
sonographer for screening and diagnosis. Like a

18 2 Normal Face
2.1 hat Is Included in a Basic

W • Continuity of the upper lip
Sonographic Survey • Profile and nose bones with usual appearance
and a Diagnostic • Orbits with usual appearance
Sonographic Survey? • Lenses with usual appearance
Elements that must appear in the second trimes- One should note that three-plane examination
ter screening report: is essential in order to exam the face:
• Continuity of the upper lip • The nose-mouth coronal plane

• The strict sagittal plane for the profile
Elements that must appear in the diagnostic • Stepped images on an axial plane, for the
report: orbits, maxilla, tongue and mandible.
Fig. 2.1 Continuity of the upper lip Fig. 2.2 Profile and continuity of the upper lip
2.2 Routine Trimester Examinations 19
2.2 Routine Trimester This is a quick analysis, which depends on the

Examinations operator’s subjectivity and enables the operator to
raise any alarms based on various key points, nota-
2.2.1 First Trimester bly using the Herman score of the sagittal image.
• Locate biparietal and back • Forehead: a smooth arch, not too domed, not
• Profile: Herman image scoring sagittal too evasive
view • Upper lip: straight, not looking like a comma
• Analysis of profile: forehead, nose, upper • Chin: aligned, individualized, not too far in
lip and position of chin advance, not too far behind
12GW 6 d 12 GW 6 d 13 GW 2 d
Fig. 2.3 Normal 2D profile
12GW 4 d
Fig. 2.4 Sagittal view, endovaginal probe

20 2 Normal Face
2.2.1.1 What 3D Can Do • A declination of the axial views: frontal arch –

Imaging volume from a strict sagittal view orbital cut – maxillary arch – mandibular arch.
enables symmetrical restitution via the three • A “surface” coronal shot: to analyze the
planes—axial, sagittal, and coronal—which are upper lip and the nose.
orthogonal to one another: • A “bone” coronal shot: to analyze the bone
mass (metopic, actual bone junctions, maxilla).
• A creation of structural symmetry, enabling • Reconstruction of the face in both surface and
one to see the strict sagittal view of the nose bone mode.
bones. • Ear insertion: height and length
a
a b c
b c
Fig. 2.5 Multiplane 3D images – different view levels

a. orbits and ears
b. maxilla and palate
c. mandible
d. orbits
multiplan 3D
different section levels
aspects of the face in3D d-orbits
11GW 5 d 12 GW
13GW 5 d
12GW 4 d 12GW 6 d
Fig. 2.6 Aspects of the face in 3D

22 2 Normal Face
Fig. 2.7 Further images of the face

“Bone” mode, the retronasal bone triangle
At 12 SA the ears seem low because they are not yet in their final position
Face in “surface” mode
Face in “bone” mode
“Bone” mode – no nasal bones
“Bone” mode – nasal bones present
2.2.2 he Second and Third

T parallel views shot during a slow sliding
Trimesters movement rotating 90°, with the circular
path ending with the nose-mouth view.
2.2.2.1 Proposed Screening Protocol 4. Arrival point: nose-mouth view.
Example for a cephalic position
Starting point: biparietal diameter 2.2.2.2 A nalysis of Sagittal
and Parasagittal Views
1. Right from the start, locate the biparietal and The objective is to clear up the profile of a slightly
the back with an oblique translation of the bent head with the chin separated from the
probe, at a distance from the biparietal diam- sternum.
eter view, using a lateral sliding movement This analysis makes it possible to check the
and then a rotation of 20–30° from its initial various locations of facial anomalies:
position.
2. Construction of the sagittal view with a 90° • the forehead
rotation of the probe around a fixed virtual • the angulation and the presence of the nasal
point. bone
3. Construction of stepped axial views, from • the form of the upper lip
the forehead to the mandible with successive • the position of the chin
Fig. 2.8 2D profile and 2D nose-mouth view

24 2 Normal Face
2.2.2.3 Analysis of the Axial Views Other views are added to this paradigm:
The axial views enable the analysis of the face • Ears
from top to bottom to view the orbits, the maxilla,
the back edge of the palate, the tongue and the At least one ear could be analyzed if the exami-
mandible. nation is normal, and with frontal views, complete
analysis of the various parts of the eye can be done.
• orbits and crystalline lenses The ears are round during the first trimester,
• maxilla slightly rimmed during the second trimester, but
• posterior edge of the palate well rimmed during the third trimester.
• position of the tongue
• mandible • Eyes: full analysis of the various elements of
the eye can be done on frontal views.
a b
b
c
c d
Fig. 2.9 Stepped views (high definition, 2D)

a-orbits
b-upper maxilla
c-posterior edge of bone palate
d-mandible
Fig. 2.10 Normal ears

12 GW
22 GW
32 GW
Auricular hypoplasia Pre-auricular
Folds sup edge of helix: Folds upper edge of helix

Down's syndrome
Fig. 2.11 Abnormal ears

26 2 Normal Face
Fig. 2.12 Frontal view of

the eye
Orbit, crystalline lens and
pupil, 32 GW
2.2.2.4 Analysis of the Frontal View Two remarks about the subjective analysis of
• Nose-mouth view: This comes at the end of the face during the second trimester:
the circular path of analysis used on a face
presumed normal in order to obtain the view • Sometimes the mid-level can show a pseudo-
required by the basic report. exophtalmy, which is physiological.
• One must see the alignment of the nose, the • At the chin level, the fetus sometimes appears
lips and the tip of the chin. to have retroganthia as a result of having a
• Absence of visualization of the chin could be slightly bent head. This is why tools such as
an indirect sign of retroganthia. facial angle biometrics are so important.
Fig. 2.13 2D nose-mouth view

28 2 Normal Face
2.2.3 potlight on the Third

S • To capture a restitution of the skeleton in
Trimester “bone” mode, and of the face in “surface”
mode
Coronal, sagittal and axial views are sometimes
difficult to capture, particularly when the exami- • When the captured images are of good quality,
nation is done at 32 GW, right before maternity the volume restitution in “surface” mode ren-
leave begins, on a tired patient, or a fetus that is ders an actual photographic map of the fetal
already low. face:
During the third term, capturing a perfect pro- –– Eyelid inclination and openings
file is particularly difficult, considering how the –– Eyelashes
chin is bent onto the sternum, yet one should try to –– Implantation of hair
capture it by mobilizing the fetus’s head using the –– Mouth and philtrum aspect
abdominal hand to create a slight lifting move-
ment in order to eliminate the possibility of real The technique for capturing 3D volume
retroganthia, which would require a level-three depends on which rendering one is looking for.
team at birth and a pediatric team with ENT skills. An aesthetic rendering of the face is possible
An important part of the routine is checking from a capture that takes in three-quarters of the
the nose-mouth view to confirm that there is no fetal face in an oblique sagittal view.
labial cleft. One should do this, not so much An analytical “anthropometric” rendering
because such a cleft is a neo-natal emergency, but of the soft parts and the bone structures of the
rather because it could be the sign that one should face requires a capture from a strict sagittal view.
look for other syndromes. An important moment in the examination:
KNOWING HOW TO PLACE THE PROBE
2.2.3.1 What 3D Can Do FOR 2D AND 3D.
During the second and third trimesters, a 3D Placing the ultrasound probe is essential for
ultrasound enables one: both the 2D view and for quality 3D capturing:
the best example is that of visualizing the poste-
• To create symmetry of the views and the posi- rior edge of the palate.
tion of the tongue Normal – Additional sagittal view – Normal –
Face examination done
• To work with the three planes—sagittal, axial Abnormal – Additional sagittal and axial
and coronal, or the different views that are use- views – Normal – Abnormal – Send patient to
ful for ultrasound diagnosis of a normal face. referring ultrasonographer.
a b
Capturing a strict profile in A, pinpointing the perfect position in B and C,

and then 3D reconstruction
Fig. 2.14 Capturing a strict profile in (a), checking the perfect position in (b) and (c), and then 3D rendering
30 2 Normal Face
Fig. 2.15 Use of the 2-mm “thick view” with a mix of max mode and x-ray mode in order to accentuate the contrasts
Fig. 2.16 Use of the omniview mode with the 2-mm “thick slice”
1. Sup. maxilla, palate
2. Frontal view with anterior portion of the mandible and the maxilla
3. Frontal view of palate
Fig. 2.17 It may be necessary to visualize the bone structures (with maximum mode)
Profile with sutures. Face: note separated nasal bones. Occipital bone, note the presence of two bones
Fig. 2.18 Various surface modes

Surface texture
Gradient light
Mix of gradient light and texture
Surface texture
Enhanced surface
Mix enhanced and smooth
32 2 Normal Face
Fig. 2.19 Placement of the probe to look for the posterior edge of the bony palate
Fig. 2.20 Placement of the probe for a sagittal view

Starting 2D view
3D result
34 2 Normal Face
Fig. 2.21 Placement of the probe for an oblique view

Starting 2D view
3D result
Fig. 2.22 Placement of the probe under the chin. Starting 2D view
3D result
Coronal view
Nose-mouth view
Normal Abnormal
Additional Additional sagittal and

sagittal view axial views
Normal
Normal Abnormal
Facial Send the patient to referring

Fig. 2.23 Coronal view— examination ultrasonographer
nose-mouth view complete
36 2 Normal Face
2.3 Biometrics of the Face 2.3.1 hickness of the

T
Forehead Skin
Most of the biometric information useful for
diagnosis is measurable: It is measured at the level of the synostosis of the
nasal bone, from the external edge of the frontal
• Strict sagittal view bone to the external edge of the skin, and it makes
–– prefrontal thickness it possible to objectify sub-cutaneous edemas and
–– nasal bone facial angle filling.
–– philtrum Measurements and views of the upper lip at
–– superior facial angle 22 GW and 32 GW on the nose-mouth image
–– inferior facial angle and the sagittal image.
• Strict axial view
–– inter-orbit distance
–– maxilla width
–– mandibular width
• Coronal view
–– one the nose-mouth view, no additional
biometrics
Table 2.1 22 GW 3.8 mm ± 0.6 mm; 32 GW: 5.93 mm ±

1.1 Levaillant N=638
GA Skin thickness compared to
(weeks) forehead (mm) average SD
21 3.44 0.65
22 3.8 0.63
23 3.84 0.61
24 4.22 0.89
25–26 3.91 0.7
27–28 4.83 0.8
29–30 5.16 0.91
31–32 5.78 1.1
33 5.93 1.1
2.3 Biometrics of the Face 37
6.3
6
5.7
5.4
5.1
4.8
mm
4.5
4.2
3.9
3.6
3.3
3
21 22 23 25 24 26 27 28 29 30 31 32 33
GA (weeks)
Fig. 2.24 Skin thickness

38 2 Normal Face
2.3.2 Length of Philtrum those that are very long, unbalancing aesthetic of
the mid-level of the face.
This is measured from the nasal septum to the
extremity of the white lip and makes it possible
to differentiate normal-length upper lips from
Table 2.2 22 GW: 6.15 mm ± 0.7; 32 GW: 7.4 mm ±

1.37. (J.M. Levaillant. N=651)
GA (weeks) Philtrum (mm) average SD
21 6.06 0.99
22 6.15 0.79
23 6.44 1.03
24 6.47 0.99
25–26 6.7 1.02
27–28 7.34 1
29–30 7.02 1.36
31–32 7.4 1.31
33–34 7.65 1.29
Phitrum (mm)
Median
9
8.5
8
7.5
Phitrum (mm)
mm
7 Median
6.5
6
5.5
5
21 22 23 24 25 26 27 28 29 30 31 32 33
GA (weeks)
Fig. 2.25 Lenght of philtrum
2.3 Biometrics of the Face 39
2.3.3 The Nasal Bones extremity of the junction between the two nasal
bones.
This is an important indication for trisomy
21 and other pathological syndromes. It is
measured from the synostosis to the inferior
Table 2.3 Nasal bones Table 2.5 Nomogram of fetal nasal bone length
Gestation Mean Gestation (weeks) Mean (mm) SD (mm)
(weeks) (mm) SD −2SD +2SD 11-11 + 6 1.69 0.26
14 4.183 0.431 3.321 5.045 12-12 + 6 2.11 0.37
16 5.213 1.062 3.089 7.337 13-13 + 6 2.34 0.39
18 6.308 0.654 5.000 7.616 14-14 + 6 2.94 0.48
20 7.621 0.953 5.715 9.527 (Sivri et al. 2006)
22 8.239 1.102 6.035 10.443
24 9.362 1.300 6.762 11.962
26 9.744 1.277 7.190 12.298
28 10.72 1.459 7.803 13.639
30 11.348 1.513 8.322 14.374
32 11.580 1.795 7.990 15.170
34 12.285 2.372 7.541 17.029
(Guis et al. 1995)
Table 2.4 Fetal nasal bone length

Gestation (weeks) Mean (mm) SD (mm)
11–11.9 1.7 0.5
12–12.9 2.0 0.5
13–13.9 2.3 0.5
14–14.9 3.4 0.7
15–15.9 3.3 0.8
16–16.9 4.4 0.7
17–17.9 5.0 0.7
18–18.9 5.5 0.9
19–19.9 5.7 0.1
20–20.9 6.2 0.1
(Cuick et al. 2004)
40 2 Normal Face
2.4 Facial Angles synostosis of the nasal bones and the line of the
nasal bones themselves.
Two facial angles are useful for the objective Measurements at 22 and 32 GW
analysis of the face.
GA (weeks) Average upper facial angle SD
21–24 128.12 10.99
2.4.1 Upper Facial Angle 25–28 129.36 13.42
29–34 131.14 12.25
The upper facial angle is the angle formed
between the line of the forehead that follows the
Fig. 2.26 Upper facial angle
Measurement of facial angles
131.5
131
130.5
130
129.5
Angle
129
128.5
128
127.5
127
126.5
21–24 25–28 29–34
GA (weeks)
Fig. 2.27 Upper facial angle
2.4 Facial Angles 41
2.4.2 Lower Facial Angle Measurements at 22 and 32 GW
The lower facial angle is the angle formed GA (weeks) Average lower facial angle SD
between the line of the forehead that follows the 21–24 65.1 7.79
synostosis of the nasal bones and the line of the 25–27 67.2 8.43
nasal bones themselves. 28–34 69.06 7.96
JM Levaillant, N = 618
Fig. 2.28 Lower facial angle
Measurement of facial angles
69.5
69
68.5
68
67.5
Angle
67
66.5
66
65.5
65
64.5
64
21–24 25–27 28–34
GA (weeks)
Fig. 2.29 Lower facial angle

42 2 Normal Face
2.4.3 easurements of the Inter-

M Average median interorbital
orbital Distance GA (weeks) distance SD
21 24.24 1.61
Interorbital distances—internal to internal, 22 25.26 1.25
middle to middle, and external to external— 23 25.97 2.32
are measured on the axial view. 24 27.04 1.59
Interorbital distance – a few points of 25–27 28, 86 1.99
reference: 28–29 30.91 2.43
Median distance: 22 GW: 25.2 mm ± 1.3 mm – 31–32 34.15 2.35
32 GW: 34.8 mm ±2.5 mm 33–34 34.49 2.14
Interorbital distance/biparietal: 22 SA: 0.47 ± JM Levaillant, N = 325
0.5 – 32 SA 0.42 ± 0.5
Measurements at 22 GW and at 32 GW for
the three distances.:
Fig. 2.30 Interorbital distance, via different methods:

int./int., middle/middle, ext./ext
35
34
33
32
31
30
29
mm
28
27
26
25
24
23
21 22 23 24 25 26 27 28 29 31 32 33
GA (weeks)
Fig. 2.31 Median interorbital distance
Table 2.6 Average internal interorbital distance Table 2.7 Average External interorbital distance
Average internal interorbital Average external interorbital
GA (weeks) distance SD GA (weeks) distance SD
21 13.66 1.49 21 34.4 2.56
22 14.09 1.42 22 36.05 2.22
23 14.22 1.57 23 37.55 2.71
24 14.57 1.89 24 39.35 2.1
25–26 15.27 1.81 25–26 40.98 2.72
27–28 16.47 1.56 27–28 43.35 2.48
29–30 16.5 1.63 29–30 48.71 2.75
31–32 17.65 2.19 31–32 50.05 3
33–34 18.14 2.26 33–34 50.84 3.07
JM Levaillant N = 660 JM Levaillant N = 618
19
18
17
16
mm
15
14
13
12
21 22 23 24 25 26 27 28 29 30 31 32 33
GA (weeks)
Fig. 2.32 Internal interorbital distance
52
51
50
49
48
47
46
45
44
43
42
mm
41
40
39
38
37
36
35
34
33
32
21 22 24 25 26 27 28 29 30 31 32 33 34
GA (weeks)
Fig. 2.33 External interorbital distance

44 2 Normal Face
2.4.4 easurements and Views

M Measurements at 22 GW and at 32 GW
of the Mandibular These profiles, all different, are either from
and Maxillary Width normal fetuses or those with trisomy 21. Can
you tell the difference? (solution on next
These measurements are made on axial views, page).
from the external edge of the bone, 10 mm in,
or more or less at the level of the canines.
Table 2.8 Maxilla width (J.M. Levaillant. N=79)

GA (weeks) Average maxillary width (mm) SD
22 24.81 3.67
23 26.19 4.05
24 27 4.14
Table 2.9 Mandibula width (J.M. Levaillant. N=79)

GA (weeks) Average mandibular width (mm) SD
22 24.15 2.64
23 25.39 2.53
24 25.4 2.16
Fig. 2.34 Width of the mandible. 22 GW: 23.8 mm ± 1.9.

32 GW: 31.9 mm ± 4.7
Mandible/maxilla ratio: 1.01 ± 0.1
Fig. 2.36 Mandibular width
Fig. 2.35 Maxilla width
Prefrontal Hypoplasia
Achondroplasia Hypoplasia Unilateral
edema of the mid- Retrognathia
domed forehead of nasal bones cleft
4P- level
Bilateral
cleft
Fig. 2.37 Sagittal View – screening for rare, but serious, facial pathologies
46 2 Normal Face
A B C
D E F
Fig. 2.38 A: Retrognathia; B: 4p-; C: Binder; D: Achondroplasia; E: Bilateral cleft; F: Unilateral cleft
Fig. 2.39 Specific interest of 3D ultrasound images in the skin surface mode
Profiles of various fetuses at 32 GW. The black background effect is created by cutting the face volume in half
48 2 Normal Face
Fig. 2.40 Comparing profiles at 32 GW and birth
a b c d e
f g h i j
Fig. 2.41 Ten fetuses, five with trisomy 21. Which ones
2.4.4.1 Comments enable greater analytical precision of the skin

As with 2D ultrasound, 3D imagery makes it pos- surface.
sible to make a subjective diagnosis that must Solution: the Down’s syndrome fetuses are b,
then be upheld by objective biometrics: that is the d, f, h, j.
finality of this analytical approach.
The HD Live lighting technique highlights
skin details, like images in dermatology.
Palpabral orientation, the sometimes
reduced width of the mouth, the more or less
visible nostrils and philtrum, are details that
50 2 Normal Face
2.5 Practical Review Work • Table 2.12 classes the markers to look for the
major deletions
• Table 2.10 is oriented by organ.
• Table 2.11 is for finding the most common These are not, of course, exhaustive tables, but
markers for major chromosomic abnormalities. practical guides to help ultrasonographers.
No modification of the
surface light position
Fig. 2.42 HD Live surface mode

With not modification of the light source position
The same volume with different light source positions
2.5 Practical Review Work 51
Fig. 2.43 Fetal faces in HDLive mode

52 2 Normal Face
white lip
blanche
red lip
philtrum
columns
philtrum groove
edge of white lip
Cupid’s bow
Fig. 2.44
2.5 Practical Review Work 53
Fig. 2.45 4 trisomy 21 fetuses

54 2 Normal Face
Table 2.10 Prenatal screening of face abnormalities from ultrasound views

Views Key organ visualized Anomalies–diagnosis
Coronal view Orbits and eyes Anomaly of position
Biometric distance
Hypo or hypertelorism
Size: microphtalmy or anophtalmy
Cataract
Eyelids and contours Angle anomoly
Presence of a daryocystocele
Nasal bones Morphological anomoly
Disjointed bones
Hypoplasia
Philtrum Long
Smooth
This with barely visible pillars
Sagittal view Forehead Very arched
Nasal bones Biometric hypoplasia
Chin Retrognathia
Prognathia
Larger or smaller facial angles
Axial view Orbits Visualisation of crystalline lens anomalies
Tongue Glossoptosis type position
Macroglossia
Mandible “U” shaped
Table 2.11 Prenatal screening for face abnormalities from ultrasound views
Trisomy 21 Trisomy 18 Trisomy 13 Trisomy 9
Forehead Sometimes domed Sloping forehead Sloping forehead Sloping forehead
Prefrontal edema
Nose Hypoplasia of nasal Big, long
bones
Philtrum
Maxillary et palate Narrow palate – Labiomaxilliaray
palatal cleft palatal cleft
Mandible Retro and Retro and micrognathia Retro and
micrognathia micrognathia
Ears Small and low Small and low Low Low, prominent
anthelix
Microcephaly + + +
Tongue Macroglossia
Eyes Palpebral clefts up Hypertelorism – fentes Palpebral clefts up
and back Palpebral clefts down and back
and back
Mouth Small mouth
2.5
Table 2.12 Microdeletions and facial dysmorphism

Practical Review Work
Deletion
17p11,2 Deletion 15q11
Deletion 22 Deletion 4p16,3 Deletion 7q11 Deletion 17p13,3 Smith- Deletion 5p15 –q13
Digeorges Wolf Hirschhorn Williams Miller Dicker Magenis Cri du chat Prader Willi
Forehead + Prefrontal edema Large forehead High Bifrontal
narrowness
Nose + Greek helmet aspect Bulbous nose tip Anteverted Sunken Wide nose root
nostrils – short mid-level
nose
Philtrum + Short Long and smooth Thick and
long
Maxillary et palate Palatal or Ogival and narrow Ogival palate
velar cleft palate
Mandible Micrognathia Retrognathia Retrognathia
Ears Dysplasia and Low ears
auricular appendage
Microcephaly + +
Tongue Hypertelorism Hypertelorism Lengthened cleft
Eyes Falling corners Thick lips Falling Falling corners
mouth
55
Clefts and Pierre-Robin Syndrome
3
3.1 Clefts There is clearly a predominant association

between the face and the brain (Table 3.1).
3.1.1 Introduction
3.1.1.3 Facial Clefts and the
3.1.1.1 Why screen? Nose-Mouth Image During the
Facial clefts are found in 272 different syndromes, Second and Third Trimesters,
the frequency of cleft lips and palate is 0.5/1000, at 22 GW and 32 GW
or 1/500, 41 % of which are associated with other The classic entry point for facial clefts is on the
organ anomalies, and only 6/10 being isolated. “nose-mouth” image, with analysis of the upper
lip, the philtrum and below the septum.
3.1.1.2 F ace and Brain: The Key A lip cleft is the starting point for labio-
Combinations of Pathologies maxillary and/or palate clefts.
to Know The second trimester report can no longer be
When a facial cleft is discovered, complete analy- written with such laconic sentences as “face
sis of the face associated with a morphological unseen during this examination.”
diagnostic study should be done, due to the fre- Now, during the second trimester of
quent association between clefts and pathological pregnancy, one should be able to effectively
syndromes, as was confirmed in this study by screen for facial clefts, at the very least cleft
Gérard Couly, done at the Necker Hospital in Paris. lip.
Table 3.1 Brain malformations associated with facial malformations

Facial malformations Brain malformations
Labio-maxillary and 170 Unilateral 135 1 lissencephaly + (epilepsy) 14
velo-palatal and Philtrum 1 agenesis of corpus callosum
abnormalities Bilateral 35 10 holoprosencephaly
1 encephalocele (Meckel)
1 cortical malformation
Maxillo-madibular 44 Francescetti S. 1 agenesis of corpus callosum 6
dysplasias Goldenhar S. 5 posterior fossa anomalies (cyst,
1st arch S. mega cisterna)
Pierre Robin syndrome 60 3 mega cisterna magna 4
1 occipital porencephaly

58 3 Clefts and Pierre-Robin Syndrome
3.1.2 Symptomatic Analysis • For each side, describe as one would a unilat-
of Clefts eral labial cleft
–– The right and left processes
3.1.2.1 Unilateral Cleft Lip –– The skin surface and mucosa on either side
This is characterized by the bi-partitioning of the of the cleft.
peri-buccal integuments and muscles and respects
the gums and the dental alveoli in the upper maxilla. The sagittal and para-sagittal views enable
It is possible to describe: one to the complete the examination with obser-
vation of related markers:
• The cleft side.
• The right and left processes. • Position of the tongue
• The skin and mucosa on either side of the cleft, • Orbits
the nostril bridge and nostril asymmetry. • Bone structure: zygomatic arch, malar bone.
• The seriousness of the defect on the median • Visualization of the soft palate.
level and particularly at the philtrum level.
The axial view, or more precisely the stepped
3.1.2.2 Bilateral Cleft Lip axial views:
This is characterized by the tri-partitioning of the These will make it possible to see to what
peri-buccal integuments and muscles, and respects extent the cleft impacts the maxilla, the back side
the gums and the dental alveoli in the upper maxilla. of the palate and the pterygoid apophyses, the
It is possible to describe: tongue position and the mandibular arch.
• The median process, under the nostrils 3.1.2.3 What 3D Can Do

• The surface of the skin on the median process, Multi-view sagittal and axial views, in TUI
and how much excess mucosa there is. mode associated with thick VCI mode views.
• Mucosa The study of millimetric views enables the
• Skin detailed analysis in three planes for possible
• The two clefts on either side of the median deformations of bone structures.
process and their possible asymmetry.
3.1 Clefts 59
Fig. 3.1 Labioalveolar-palatal cleft. Overview in three planes
Fig. 3.2 Labioalveolar-palatal cleft. Axial view
Fig. 3.3 Labioalveolar-palatal cleft. Axial view
3.1.3 Ultrasound Diagnosis unilateral cleft, or a tri-partitioning in the case of

of Clefts: Analytical Study a bilateral labio-maxillary cleft.
An open-mouth sagittal view is rather easy
Once the diagnosis of a lip abnormality has been to capture for an examination targeting the palate,
uncovered, the ultrasonographer must use a sim- and enables one to follow both the hard and soft
ple, strict diagnostic methodology: palates. The image is almost easier to capture at
this stage than during the second trimester,
• Description of the cleft lip because there are fewer shadows linked to
• Description of the cleft maxilla if there is one ossification.
• Description of the cleft palate if there is one.
What 3D Can Do
3.1.3.1 A nalytical Study of First Skin surfacing objectifies the processes well.
Trimester Clefts The multi-planar technique and using thick
On the Herman score sagittal view, the upper lip views makes it possible to capture stepped axial
could have a comma-shaped deformation, with slight views starting from the orbit on to of the man-
eversion of its inferior portion, which should alert the dibular cavities.
ultrasonographer that there may be a cleft lip. It is easier to look for associated anomalies
The nose-mouth view can then show the during the first trimester. With trisomy 13, the
defect. associated hexadactylism can be seen in the same
Maxillary and mandibular axial views are 3D volume, and for that reason, one must record
easy to capture and can show the bi-partitioning the largest volume possible.
of the facial mass if there is a labio-maxillary
3.1 Clefts 61
Fig. 3.4 Uniliteral labioalveolar cleft at 12 GW
© R Chaoui
Otocephaly Trisomy 13
facial dysmorphism and
hexadactylism
Fig. 3.5 Otocephaly
The frontal view demonstrates an intact palate
Fig. 3.6 Unilateral labial cleft

3.1 Clefts 63
3.1.3.2 A
nalytical Study of Clefts Unilateral labio-alveolar-palatal cleft.
from the 2nd Trimester Bilateral labio-alveolar cleft impacting the
The most favorable time frame is between 20 and primary palate, with an intact secondary palate.
25 GW. Median cleft: a particular and associated
The major types of clefts: pathology.
Unilateral cleft lip.
Reconstructed 3D views of the palate demonstrate the palatal

cleft
Fig. 3.7 Labioalveolar and palatal cleft
The cleft involves the primary palate,

but the secondary palate is intact, as clearly
visible on these frontal views
Fig. 3.8 Bilateral labioaveolar-palatal cleft. 3D reconstructed views of the palate
Fig. 3.9 17 GW median

cleft lip – trisomy 13 HDLive surface mode Maximum mode shows maxillary cleft
3.1 Clefts 65
Fig. 3.10 Labioalveolar and palatal cleft, stepped axial views
3.1.3.3 B asic Principles for Obtaining • frontal mode

2D and 3D Views • flipped mode
Position of the head: • reverse mode
The position of the fetal head during image
capture is important for precise rendering and for Sagittal, axial and coronal views:
the diagnosis. By associating the various modes, such as
thick 2-mm views, multiplanar mode and TUI
1. A denected position is used to capture and mode, one can capture anatomical images of the
render images of the primary and secondary various views in order to study the entire head in
palates. detail, from the integuments to the bone
2. In 3D, one can approach the palate in three ways: structure.
Fig. 3.11 Three ways to look at the palate from a volume image: frontal, flipped or reverse modes
3.1 Clefts 67
Classic" surface mode HD Live mode
Fig. 3.12 Unilateral labioalveolar-palatal cleft
3.1.3.4 H D LIVE: Contribution In this evaluation, it is important to look at two

to an Aesthetic Prognosis tissues:
Variable directional lighting software can enable
more detailed analysis of the soft tissue. In the • The lip skin surface on the cleft side
case of cleft lip, it is particularly interesting to • The volume of the red lip on the same side,
differentiate the white and red lips and help the compared to the cleft’s contralateral side.
surgeon develop a prenatal estimation of the plas-
tic repairs needed for the upper lip.
3.1.4 Cleft Algorithm 3.15, and 3.16: unilateral labial cleft, bipartition
of the primary palate, normal palate, and palatal
An example of the cleft algorithm, in the case of cleft.
a unilateral cleft lip, is shown in Figs. 3.13, 3.14,
Unilateral cleft lip
Axial view Axial view Axial view
Normal alveolus Non linear lining Bipartition of

of the alveolus the maxilla
Isolated cleft lip Labioalveolar cleft Alveolar notching
Fig. 3.13 Unilateral labio-alveolar-palatal cleft with tongue protrusion in the cleft. “Classic” surface mode. HD Live
mode
3.1 Clefts 69
Normal alveolar arch deformed alveolar arch alveolar arch with wide
defect
Fig. 3.14 Bipartition of the primary palate
Fig. 3.15 Normal palate
Fig. 3.16 Palatal cleft
3.1.5 ltrasound Diagnosis of

U the different cases of facial clefts: Unilateral and
Labioalveolar-Palatal Clefts: bilateral cleft lip; unilateral and bilateral cleft
Summary alveolus; unilateral and bilateral cleft hard palate;
posterior clefts, premaxillary agenesis and holo-
Tables 3.2, 3.3, 3.4, 3.5, and 3.6 summarize what prosencephaly syndrome, respectively.
to look for and find on each of the image views in
Table 3.2 Ultrasound of unilateral and bilateral cleft lip

Image view Unilateral cleft Bilateral cleft
Sagittal No direct image
The indirect signs are: comma-shaped columella The expected normal image is replaced by a
and loss of lip regularity. budding growth of tissue resulting from pre-
maxillary protrusion.
A para-sagittal slice can visualize the cleft There are two defects on the parasagittal image,
upper lip: a defect causing asymmetry in cupid’s dividing the facial mass into three.
bow
The nostrils can be seen, complete but
asymmetrical.
Axial Bipartition of the lip with a solution for The median process is very much in front of the
continuity. two lateral lip lines, creating a division of the lip
Asymmetrical nostrils – the nostril is intact on the into three.
cleft side, flattened and widened. Nostrils are symmetrical and complete.
Coronal This is an important view. The nose-mouth This is an important view.
image required for the basic report.
The unilateral cleft can be seen when the slice is The division into three of the lip and the process
perfect, without the interposition of a limb or the “set” under the nostrils is clear.
cord.
Table 3.3 Ultrasound of unilateral and bilateral cleft alveolus

Image view Unilateral cleft Bilateral cleft
Sagittal or The para-median zone at the level of the cleft lip The pre-maxillary process is projected toward
para-sagittal shows an anechogenic defect and alveolar the front.
absence, more pronounced depending on the size Morphological analysis of the process shows
of the alveolar cleft, which could go from simple the presence of soft tissue, associated with
misalignment of the alveolar arch to an alveolar structures.
anechogenic gap.
The rupture between the remaining alveolar
arch, to the left and right, appears like an
anechogenic zone.
Axial This is an important image. One visualized and Protrusion of the premaxillary and the
quantifies the degree of rupture of the alveolar prolabium.
arch, from simple disturbed alveoli to a The pre-maxillary mass can be quantified:
bi-partitioning of the facial mass. size, soft tissue, bone mass.
The separation of the facial mass into three by
full rupture of the pre maxillary respects the
symmetry of the adjacent hemi-maxillaries
and protruding pre-maxillary.
Coronal There is a defect in alveolar continuity. Continuity of the maxillary arch seen from the
To visualize, one must remain in the strict front is interrupted twice: to the left and right
maxillary arch plane. of the anterior process.
3.1 Clefts 71
Table 3.4 Ultrasound of a unilateral or bilateral cleft secondary or hard palate

Image view Cleft palate with unilateral labio-maxillary cleft Cleft palate with unilateral labio-maxillary cleft
Sagittal or Successive slices show a defect in the The bilateral cleft associated to a cleft palate is
para-sagittal secondary palate. defined in the sagittal slice by the vomer bone,
which is median, rectilinear and not deviated.
It is median, asymmetrical, sinuous, often The para-sagittal slices are the ones that enable
para-sagittal to the vomer bone, which can be the visualization of defects in the hard palate.
a “trap” on the strict sagittal slice.
Axial The important image is the deviation of the The hyperechogenic median line, perpendicular
vomer bone axis in relation to the line to the maxillary axis, represents the vomer bone.
perpendicular to the maxillary.
The angle is around 10–20° Not held back, it pushed the premaxillary toward
the front, on the median axis.
The defect is visible on both sides.
Coronal The palatal arch is interrupted by the Only the vomer can be seen, not deviated, in
anechogenic defect. suspension, with lower bone support.
The defect is situated opposite the cleft lip and From the two sides, one can visualize two little
maxillary. structures made of bone relics.
The two palatal demi-arches are asymmetrical.
Table 3.5 Ultrasound aspects of posterior clefts

View Ultrasound aspects
Palate 10 mm sagittal and The hard palate is seen on this view. It is subjectively short, inferior to 10 mm. This
para-sagittal sign is not a certain sign, often looked for in inferior facial angle anomalies such as
retrognanthia and glosoptosis.
Axial On the axial view, the posterior edge is only visible if the slice goes through the
pterygoid apophysis and the posterior palatal edge, which appears alone, in the form of
a hyperechogenic line that is continuous and very slightly concave. If there is a cleft,
the posterior edge forms an upside down V.
Coronal Successive coronal view from front to back show a bi-partitioning of the bone mass
behind the alveoli—a reference point for the primary palate. In the back, there is a
rupture of the secondary palate, at 5–6 mm from the alveolar line. In 2D ultrasound,
the successive views first show continuity of the line, then progressive flaring of the
posterior edge.
Table 3.6 Ultrasound of median clefts. Pre-maxillary agenesis. Holoprosencephaly syndrome

View Ultrasound
Sagittal or parasagittal Flat nose, prominent lower lip.
Axial No primary palate.
In the back, visualization of secondary palate.
Coronal Mucosa, labial and bone defect.
Visible primary palate
Nearly absent nose, flat
X-shaped cleft lip, limited by the nose, the lower lip and two lateral defects.
Pre-maxillary agenesis. Holoprosencephaly syndrome
3.1.6 he Decision-Making Process

T This decision-making process guides the ultraso-
After the Discovery of a Facial nographer in explaining to the parents the type of
Cleft cleft which affects the child.
The decision-making process following the dis-

covery of a facial cleft is summarized in Fig. 3.17.
Fig. 3.17 Diagnostic and Ultrasound Cleft Ultrasound for “at-

detection
treatment decision making screening risk” patient
process
Reference person
Looking for other Confirmation and

Specific tests (caryotype)`
anomalies precision concerning
the nature of the cleft
Isolated cleft Related anomalies
Submission to Referral center and prenatal maxillo-facial

consultation
Overall prognosis (related Age of diagnosis

anomalies)
Explanation of surgical
treatment
Medical interruption of
Decision Continue pregnancy
pregnancy
Obstetric, pediatric and surgical

scheduling
Birth
Feto-pathology
Examination of child
Treatment
Genetic consultation and
psychological consultation
3.2 Pierre-Robin Syndrome 73
3.2 Pierre-Robin Syndrome 3.2.1.1 R etrognathia and the Inferior

Facial Angle
Retrognathia is the first warning sign related to The inferior facial angle evolves throughout
Pierre Robin Syndrome seen on ultrasounds as pregnancy, due to suckling by the fetus, which
early as the first trimester, and in each screening modifies the angle by a few degrees.
ultrasound done at 22 GW and 32 GW, which In Pierre Robin syndrome, the inferior facial
again emphasizes the importance of a systematic angle is less than 49°.
sagittal view.
3.2.1 ow to Screen
H
for Retrognathia
A first-trimester sagittal view makes it possible to

visualize retrognathia and palate and mandibular
abnormalities.
Fig. 3.18 Retrognathia at 32 GW. Note the absence of nasal bones in this case
Fig. 3.19 Evolution of retrognathia (Pierre Robin syndrome) during a pregnancy. 12 GW, 24 GW and 32 GW.
Retrognathia is most visible at the beginning of the pregnancy
3.2.1.2 Axial View of the Jaws A normal mandible forms a near triangle, in a
From the 12th week, the shape of the mandible in V shape, while a PRS mandible forms the
Pierre Robin syndrome is very different. rounded arc of a circle.
Normal mandible at 12 GW Pierre Robin mandible at 12 GW
Fig. 3.20 Shape of a normal mandible and of a mandible in case of Pierre-Robin Syndrome
palate
defect
post. palate
tongue
Fig. 3.21 Retrognathia with glossoptosis and posterior cleft palate at 15 GW

Screening Detecting High risk patient

ultrasound retrognathia ultrasound
Reference ultrasound
Complete morphological analysis
Facial analysis:
Measurement of facial angle (P.R.S. < 49°)
Glossoptosis and backwards displacement of tongue
Posterior cleft palate
Testing for anomalies Specific investigations-Caryotype
Submission to referral center

Genetic consultation to look
for syndrome
DECISION
Related abnormalities Continue pregnancy
Medical interruption Obstetric, pediatric and

of pregnancy surgical scheduling
BIRTH IN LEVEL 3 MATERNITY with

FETOPATHOLOGY ENT unit specialized in the syndrome
Fig. 3.22 Diagnostic and decision-making process in case of Pierre-Robin syndrome
3.2.1.3 Glossoptosis tence, facial dysmorphism, and learning

Verticalization of the tongue can be seen as early difficulties. (N. Philip)
as the first trimester. Its intra-buccal position is A diagnostic ultrasound that reveals ret-
displaced backwards in comparison to the normal rognathia should lead to a search for heart
position, where the anterior extremity of the disorders, and similarly, any discovery of a
tongue is located right behind the jaws. conotruncal heart disorder should lead to a
search for cleft palate, and even a posterior
cleft.
3.2.2 hat to Look for in Cases
W
of Retrognathia 3.2.2.3 Fetal Alcoholism
Fetal alcohol syndrome (FAS), which is some-
Retrognatia is the warning sign, and leads imme- times called alcoholic embryopathy, is the alco-
diately to a search for glossoptosis and cleft pos- holic intoxication of the embryo or fetus resulting
terior palate. from the mother drinking during pregnancy.
The diagnostic trio will lead to a complete
morphological examination due to the large num- • Intrauterine growth deficiency. The growth
ber of congenital syndromes linked to the trio, deficiency is global, and touches weight,
the four most important of which, in order of fre- height and cranial perimeter. The children are
quency are: born weak, fragile and often prematurely.
• Craniofacial dysmorphism. FAS leads to a
3.2.2.1 Stickler Syndrome specifically shaped baby head, with small pal-
Stickler syndrome is a hereditary vitreoretinopa- pebral fissures, a marked nasal hollow, a bump
thy with ocular problems, a Pierre Robin between the eyes, low and unstuck ears,
sequence that is more or less complete, bone microretrognathia (small mandible that is too
abnormalities and neuro-sensory deafness (10 % far back), a thin and convex upper lip, ante-
of cases). verted nostrils (excessively turned toward the
Incidence at birth is estimated at around front), long and bulging philtrum.
1/7,500. • Malformations touch around 25 % of cases,
Ocular anomalies can include juvenile cataract, and can impact the brain, heart, urinary
myopia, strabismus, vitreoretinal or chorioretinal tract, etc.
degeneration, retinal detachment, and chronic uve- • Psychiatric troubles appear after birth, some-
itis. Bone abnormalities include discrete platyspon- times during childhood.
dylia and often voluminous epiphyseal damage • Immediate alcohol withdrawal syndrome with
(Martine Le Merrer-Orphanet). tremors and trouble sleeping.
The diagnostic ultrasound cannot guarantee • Hyperactivity during childhood with irritabil-
parents the absence of Stickler syndrome on ity, attention deficit, difficulties concentrating.
the second and third trimester ultrasounds. • Mental retardation. Studies have demonstrated
that a mother consuming three glasses of alco-
3.2.2.2 The 22q Deletion hol a day leads to a child’s loss of an average
Monosomy 22q11 or DiGeorge Syndrome is of 7 IQ points.
characterized by a combination of several mal- • Poor muscle tone, memory and fine motor
formations, including thyroid and parathyroid skills.
hypoplasia, conotruncal congenital heart dis-
orders, and slight but distinctive facial There are several approaches to the diagno-
dysmorphism. sis on ultrasound, including the facial dysmor-
The velocardiofacial syndrome, in its full phism and microretrognathia, growth
form, combines congenital conotruncal heart dis- deficiencies—an excellent biometric marker—
orders, cleft palate or velopharyngeal incompe- and of course the heart and the brain.
3.2.2.4 Treacher-Collins Syndrome GROUP 2 – the 26 rarest syndromes

Treacher-Collins syndrome is a congenital disorder
affecting craniofacial development, characterized Orofacial digital syndrome
by bilateral and symmetric oto-mandibular dyspla- Nager syndrome
sia without limb anomalies, associated with a vari- Silver Russel syndrome
ety of head and neck abnormalities. The annual Trisomy 22
incidence is estimated at 1/50,000 live births. Trisomy 21
Children show characteristic facial dysmorphism, Vaproate syndrome
with bilateral and symmetric hypoplasia of the Hemifacial microsomia
malar bones and the infra-orbital opening (80 % Cerebral ocular facial syndrome
cases) or the mandible (78 %) (retrognathia, retro- Marshal syndrome
genia), which leads to dental malocclusion, charac- Cerebral costo mandibular syndrome
terized by anterior open bite. Predominant Kabuki syndrome
hypoplasia of the soft tissues can be observed at the Atelosteogenesis type 3
malar level, around the lower orbital edge and on Beckwith Weidemann syndrome
the cheeks. One can also observe complex anoma- Distal anthrogryposis
lies in the temporomandibular joint responsible for Bilateral femoral dysgenesis
limitation in buccal opening that can be of variable Catel-Manzke syndrome
severity, down-slanting palpebral fissures (89 %) Klinefelter syndrome
and colobomata of the lower eyelids at the 1/3 exter- Non-ocular Stickler syndrome
nal-1/3 middle union (69 %) with absence of eyelids Miller Dieker syndrome
on the external third of the lower eyelid. The palate Spondyloepichyseal syndrome
is ogival, and cleft palate could be observed (28 %). Dysplasia
External ear anomalies such as anotia or microtia, Moebius syndrome
atresia of the external auditory canals and anoma- Pterygium popliteal syndrome
lies in the ossicular chain are often present (60 %) Soethre Chotzen syndrome
and lead to conduction deafness. Intelligence is gen- Adam sequence
erally normal. Respiratory and nutrition difficulties Diastrophic dysplasia syndrome
can be encountered during early years, resulting for Larsen syndrome
the narrowness of the upper respiratory passages
and the limitations in the buccal opening. (M-P Table 3.22 shows the importance of having
Vasquez) a pluridisciplinary team in helping with the
The diagnostic ultrasound revealing any choice of continuing pregnancy as well as in
retrognathia should look for abnormalities in the continued research for syndromes that
the external earls and the semi-circular canals, could lead to a medical interruption of the
the most frequent related sign, which often pregnancy.
only touches one ear and supports a presumed
Treacher-Collins syndrome.
3.2.2.5 P
ierre Robin Syndrome: Non-
isolated Syndrome
GROUP 1 – The 4 most frequent syndromes
Stickler syndrome 34 %
22q.11 deletion 11–15 %
Fetal alcohol syndrome 10 %
Treacher-Collins syndrome 5%
Dysmorphism
4
4.1 ow to Define Objective

H among other things, enable a precise measure-
Facial Dysmorphism ment of the inter-orbital diameter.
The coronal view will, as shown in other
The study of fetal face anomalies using precise, chapters of this book, be an important tool to
reproducible, anthropometric criteria helps avoid evaluate labioalveolar-palate defects.
the too-frequent subjectivity found in an approach A panel of measurements covers the various
that is not truly quantified. The discovery of dys- facial parameters.
morphism and its characterization is one way that For a clear presentation, we decided to subdi-
is frequently used to uncover various pathologi- vide the most common dysmorphic pathologies
cal fetal syndromes. that impact the face into five categories:
• Major chromosomal anomalies

4.2 Tools for This Study • Pathologies impacting primarily the upper
face
They were described in Chap. 1 and consist of: • Pathologies impacting primarily the mid-face
Volume ultrasound images that enable: • Pathologies impacting primarily the lower face
• Unclassifiable pathologies
• Capturing rigorously strict views using multi-
ple plane views and their orthogonality
principle. 4.3 ysmorphism of Major
D
• Demonstrative imagery with surface render- Chromosomal Anomalies
ing modes
• An evaluation of the bone structures with the Screening for the major chromosomal anomalies
“maximum” mode. currently depends on quality screening during the
first trimester. In this chapter, we will identify the
Thus, the study of the sagittal view, espe- principal characteristics of the dysmorphism
cially with a study of the facial angles, is a key related to the major chromosomal anomalies.
moment in the study of the fetal profile, which is
very often altered in cases of facial
dysmorphism. 4.3.1 Trisomy 21
The axial view will contribute key informa-
tion regarding the shape and size of the maxillary There is frequently a delay in the ossification of the
bones and particularly the mandible, and will, nose bones (Figs. 4.1 and 4.2), the forehead could

80 4 Dysmorphism
be domed, sometimes with a prefrontal edema palpebral fissures are directed up and behind
(Fig. 4.3), the features could appear flat without the (Fig. 4.7), the ears are small and low (Fig. 4.8), and
upper facial angle truly being modified (Figs. 4.4 the tongue could be protrusive (Fig. 4.9).
and 4.5a, b), the mouth is small, with corners that to Nevertheless, in a certain number of cases, the
not exceed the wings of the nose (Fig. 4.6a, b), the profile could appear normal (Fig. 4.10).
Fig. 4.1 Nasal bone not visible at 13 GW (multiplanar view)
4.3 Dysmorphism of Major Chromosomal Anomalies 81
Fig. 4.2 Nasal bone not visible at 15 GW (multiplanar view)
Fig. 4.3 Prefrontal edema 22 GW

82 4 Dysmorphism
Fig. 4.4 Flat features
a b
Fig. 4.5 (a) Increased upper facial angle 18 GW; (b) Normal facial angle at 22 GW
a b
Fig. 4.6 Small mouth: (a) 22 GW; (b). 32 GW
Fig. 4.8 Small ear at 26 GW
Fig. 4.7 Palpebral fissures oriented up and back

84 4 Dysmorphism
Fig. 4.9 Protrusive tongue
Fig. 4.10 Trisomy 21, normal profile
4.3.2 Trisomy 18 In these case, the dysmorphism associates

microretrognathia, sloping forehead, and
The diagnosis of this chromosomal anomaly is small low ears. Cleft palate is frequent (cf.
usually based on a collection of morphological Clefts)
anomalies.
Fig. 4.11 Microretrognathia at 13GW (multiplanar image)

86 4 Dysmorphism
Fig. 4.12 Microretrognathia at 13GA, rendered image Fig. 4.14 Small ear
a b
Fig. 4.13 (a) Sloping forehead and (b) microretrognathia
4.3.3 Trisomy 13 These anomalies are related to cerebral medial

line anomalies (alobar, semi-lobar or lobar holo-
Dysmorphism in the case of trisomy 13 is often prosencephaly) that are present in 50 % of cases.
very spectacular, covering a wide range of possi- Facial dysmorphism related to other chromo-
bilities from a simple median incisor (Fig. 4.15) somal anomalies are often rougher, as seen in the
to cyclopia (Figs. 4.16 and 4.17), with a full below examples corresponding to:
range of intermediary aspects possible including
more or less hypotelorism (Fig. 4.18), single nos- • A partial trisomy 8 with an everted lower lip, a
trils (Figs. 4.18, 4.19, and 4.20). Clefting is found round nose and retrognathia (Figs. 4.23 and 24).
in 60–80 % of cases, and is both unilateral and • Distal monosomy 6P, with related hypertelorism,
bilateral. Median clefts are characteristic very slight retrognathia, palpebral fissures ori-
(Figs. 4.21 and 4.22). ented down and out, low-set ears (Fig. 4.25).
Fig. 4.15 Median incisor

88 4 Dysmorphism
a b
Fig. 4.16 (a, b) Cyclopia, proboscis 13GW
Fig. 4.17 Cyclopia, single nostril. 22 GW

90 4 Dysmorphism
Fig. 4.18 Hypotelorism, single nostril 13GW
Fig. 4.19 Single nostril 13GW (multiplanar image)
a b
Fig. 4.20 Single nostril 22 GW:(a): Render 3D, (b): 2D
Fig. 4.21 Median cleft 14 GW

92 4 Dysmorphism
Fig. 4.22 Various fetal facial dysmorphic features related to trisomy 13
Fig. 4.23 Partial trisomy eight profile
Fig. 4.24 Partial trisomy eight (post-natal aspect)

94 4 Dysmorphism
Fig. 4.25 Distal

monosomy 6p
4.4 Upper Face Pathologies 95
4.4 Upper Face Pathologies This dysmorphism occurs in a context of early

IUGR with, in particular, severe microcephaly,
4.4.1 Wolf-Hirschhorn Syndrome mental retardation could be severe with walking
and language acquisition occurring more or less
Wolf-Hirschhorn syndrome results from a micro- late.
deletion, with an incidence of 1/50,000. The
deletion occurs on the short arm of chromosome
4 at the 4p.16.3 region. This deletion is sporadic 4.4.2 Craniostenosis
in the majority of cases. Research for this dele-
tion should be signaled to geneticists when they These anomalies, resulting from the premature
test the amniotic fluid. fusing of one or several sutures, often lead to
The dysmorphism is characteristic: severe dysmorphism. The overall incidence is esti-
mated at 1/2000 and around 100 different forms
• On the profile, the upper facial angle mea- have been described. The role of an ultrasonogra-
surement is barely inferior to normal mea- pher consists of labeling as best as possible the
surements. However, the glabella appears type of anomaly and then looking for other mark-
prominent with a frequently not very echo- ers to determine whether or not the craniostenosis
genic aspect (the prefrontal tissues), which is related to a syndrome. It is useful to remember
results in a characteristic “Greek Helmet” that the first sign signaling craniostenosis could be
look (Fig. 4.26). an enlargement of a healthy contralateral suture.
• The corners of the lips appear to be falling. Craniostenoses are classified based on the type
• There can also be hypertelorism, dysplastic of suture involved (Figs. 4.27, 4.28, 4.29, and 4.30).
ears with periauricular tags, cleft lip or labio- Below are a few examples of an approach to
alveolar-palatal clefting. these complex pathologies.
a b c
Fig. 4.26 “Greek Helmet” look

96 4 Dysmorphism
Metopic: trigonocephaly
Unilateral coronal: Bilateral coronal:

Anterior plagiocephaly brachycephaly
Unilateral lambdoid:
posterior plagiocephaly
Sagittal: scaphocephaly
Fig. 4.27 Classification of craniostenoses
Fig. 4.28 Trigonocephaly (premature fusing of the metopic suture)
Fig. 4.29 “Cloverleaf” skull with intra cranial marks (premature fusing of coronal sutures)
Fig. 4.30 Asymmetric craniostenosis (premature fusing of a coronal suture)

98 4 Dysmorphism
4.4.2.1 E xamples of Syndrome Apert syndrome This results in the premature

Craniostenosis closing of the coronal sutures, with broad bone
Crouzon syndrome This syndrome results in the defects that can be seen on the median line
premature closing of the coronal sutures. Facial dys- between the two fontanels. Dysmorphism is
morphism is characterized by branchycephaly, with characterized by branchycephaly, a very marked
a very domed appearance, frontal bumps, moderate nasal bridge (Fig. 4.35), moderate mid-level face
hypoplasia of the mid-level face (Figs. 4.31, 4.32, hypoplasia, hypertelorism and a prominent fore-
4.33, and 4.34), proptosis related to shallow orbits head. The hands show syndactyly that leaves the
(Fig. 4.33), slight hypertelorism (Fig. 4.33), and a thumb free, producing “mitten” hands
straight mandible (Figs. 4.33 and 4.34). Intelligence (Fig. 4.36), however syndactyly of the feet
is generally normal. Complications such as atrophy impacts all the toes.
of the optic nerves and deafness can occur if not
caught and treated early. It is an autosomal dominant
genetic disorder.
Fig. 4.31 Crouzon syndrome (multiplanar image)
Fig. 4.32 Crouzon

syndrome: profile
Fig. 4.33 Crouzon syndrome: “render”

100 4 Dysmorphism
a: Maximum mode b: Post-natal
Fig. 4.34 Crouzon syndrome, with very wide metopic suture. (a) Maximum mode; (b) Post-natal
Fig. 4.35 Apert syndrome: profile
4.4.2.2 DiGeorge Syndrome

This syndrome is linked to a microdeletion at
22.q.1.1 and occurs at a frequency of 1/4000.
Transmission is dominant; one parent is carrier of
the deletion in 10–20 % of cases, most frequently
this deletion is “de novo”.
The main markers are:
• Conotruncal heart disorders (75 %) of cases

• Hypoplasia or absence of the thymus (in 83 %
of cases if there is a heart malformation, and
in 31 % of cases if the deletion is isolated)
• Palate defects (76 % of cases: submucosal
cleft palate and cleft palate, velopharyngeal
incompetence, etc.)
• Renal anomalies (35 % of cases)
• Limb anomalies (hyperlax hands or fingers,
polydactyly)
• A broad range of psycho-motor development
anomalies (slow learning with IQ variations
from normal to seriously retarded, psychiatric
disorders in 10 % of cases).
Fig. 4.36 Apert syndrome: dysmorphism and syndactyly
producing “mitten” hands
The dysmorphism is very moderate, associ-
ation a “tubular”-looking nose (Figs. 4.37,
4.38, and 4.39), a relatively narrow mouth
(Fig. 4.39), and minimal external ear anoma-
lies (Fig. 4.40).
102 4 Dysmorphism
Fig. 4.37 DiGeorge syndrome: multiplanar image, tubular nose (image B)
Fig. 4.40 DiGeorge syndrome: ear: excessively folded

helix
Fig. 4.38 DiGeorge syndrome: tubular nose, “render”
Fig. 4.39 DiGeorge syndrome: tubular nose, small

mouth (Render HD-Live)
104 4 Dysmorphism
4.4.2.3 Microcephaly When microcephaly is discovered, on must:

Microcephaly is a clearly defined biometric
anomaly: the cranial circumference is smaller • Correlate the cranial circumference with other
than −3 SD or Z-Score : −3. The frequency of biometric parameters.
1/6200 to 1/8500 is certainly underestimated. It • Look for a vascular context.
can be isolated, related to holoproscencephaly, or • Test for infections.
associated with chromosal anomalies, a number • Do karyotype testing for a 4p- deletion
of genetic syndromes, and other morphological • Do a family survey
anomalies. • Do a detailed ultrasound, particularly of the
Three conditions are required to consider cerebral structures.
microcephaly:
Dysmorphism primarily takes the form of a
• The dating of the pregnancy and the biomet- sloping forehead (Figs. 4.41, 4.42, and 4.43) and
ric definition must be precise, and the mea- a disproportion between the size of the face and
suring technique must be irreproachable. the skull (Figs. 4.42 and 4.43).
Fig. 4.41 Microcephaly:

normal-sized face, sloping
forehead
Fig. 4.42 Microcephaly: sloping forehead, narrow skull with retrognathia

106 4 Dysmorphism
Fig. 4.43 Microcephaly:

“render”
4.5 Mid-Face Pathologies 107
4.5 Mid-Face Pathologies with macrocrania (very marked frontal bossing),

and a relatively narrow thorax (Fig. 4.45). In
4.5.1 Achondroplasia addition to these markers, the ultrasound will
show a characteristic appearance of the upper
Achondroplasia is the most frequent osteochon- femoral metaphyses, which appear to be slender
drodysplasia, with an estimated frequency like “ice cream cones,” leading to an “opening”
between 1/15,000 and 1/26,000. It is related to a of the upper femoral angle (Fig. 4.44), short tri-
mutation of the FGFR3 gene. This bone pathol- dent hands, and platyspondyly (Fig. 4.45).
ogy becomes apparent starting at 26 gestational Dysmorphism combines marked frontal boss-
weeks, the diagnosis most frequently made during and a very “hollowed” nasal bridge with an
ing the third trimester ultrasound showing very abnormally closed upper facial angle (Figs. 4.46,
short limbs, in particular rhizomelia contrasting 4.47, 4.48, and 4.49).
Fig. 4.44 Achondroplasia: slender upper femoral metaphysis (2D and 3D)
108 4 Dysmorphism
Fig. 4.45 Achondroplasia: trident hand, narrow thorax, platyspondyly
Fig. 4.46 Achondroplasia: multiplanar view

110 4 Dysmorphism
Fig. 4.47 Achondroplasia: closed upper facial angle
Fig. 4.48 Achondroplasia:

dysmorphism “Render HD
Live”
Fig. 4.49 Achondroplasia: dysmorphism “Render”

112 4 Dysmorphism
4.5.2 Maxillo-Facial Dysplasia: Dysmorphism takes the form of a flattened

Binder Syndrome midface that translates into an abnormally open
upper facial angle, a short nose with a flattened
This anomaly has an estimated incidence of root, a slightly protruding mandible, and a little
1/10,000, but is probably underestimated. A few developed upper maxilla (Figs. 4.50, 4.51, 4.52,
family recurrences suggest autosomal recessive 4.53, and 4.54). Tests should include karyotype,
transmission or low-penetrating dominance. maternal blood test for lupus, a detailed ultra-
Binder-like dysmorphism can be found in cases sound looking for punctate epiphyses (Figs. 4.55
of mothers taking phenytoin and anti-vitamin K and 4.56), a scan could be done to confirm the
type anticoagulants, or with lupus. ultrasound results. Discovery of a
This sequence is considered to be an allelic brachytelephalangy would suggest a benign form
variation of punctate chondrodysplasias. of chondrodysplasia punctate (Fig. 4.57).
Fig. 4.50 Binder, multiplanar view
Fig. 4.51 Binder, open

upper facial angle
Fig. 4.52 Binder, rendered mode

114 4 Dysmorphism
Fig. 4.53 Binder, Render HD-live mode
Fig. 4.54 Punctate calcifications: prenatal ultrasound and corresponding post-natal x-ray
Fig. 4.55 Punctate calcifications – post-natal appearance

116 4 Dysmorphism
Fig. 4.56 Brachytelephalangy: prenatal ultrasound appearance and corresponding post-natal x-ray
Fig. 4.57 Binder, post-natal appearance
4.5.3 Thanatophoric Dysplasia fashioned telephone receivers, a narrow thorax

that looks like a champagne cork on a sagittal
This is the most frequent of fatal osteochondro- view, platyspondyly with H-shaped vertebrae,
dysplasias, with an estimated 1/20,000 to and macrocrania. Hydramnios is common
1/60,000. (Fig. 4.58).
Currently, a diagnosis is made most often Dysmorphism is marked by macrocrania,
during the first trimester, although it could be mid-face hypoplasia translated by a marked nasal
made during the second trimester. It combines bridge with a reduced upper facial angle
very short limbs with femurs shaped like old- (Figs. 4.59, 4.60, 4.61, and 4.62).
a b
Fig. 4.58 Thanatophoric dysplasia: (a) narrow thorax. (b) short curved femur. (c) platyspondyly. (d) macrocrania
118 4 Dysmorphism
Fig. 4.59 Thanatophoric dysplasia: multiplanar view
Fig. 4.60 Thanatophoric dysplasia: reduced upper facial angle
Fig. 4.61 Rendered image

of thanatophoric dysplasia
120 4 Dysmorphism
Fig. 4.62 HD live

rendered image of
thanatophoric dysplasia
4.5.4 Prader-Willi Syndrome to diminished active movements, fetal cardiac

disorders, and genital anomalies, and a detailed
This rare syndrome affects between 1/10,000 and study of the face could then support the
1/25,000 births, its origin being a genetic deletion on hypothesis.
the paternal chromosome 15 (at 15q11-q13). It is: Dysmorphism in this syndrome is character-
ized by:
• Either de novo
• or part of a maternal uniparental disomy. • A thin, slightly turned up upper lip
• Almond-shaped eyes, narrow forehead
Prader-Willi syndrome is considered with the • A closed upper facial angle
discovery of hydramnios and slow growth related
Fig. 4.63 Prader-Willi Syndrome: closed upper facial angle, thin turned up upper lip
a b
Fig. 4.64 Prader-Willi Syndrome: rendered image

122 4 Dysmorphism
4.5.5 Otopalatodigital Syndrome gers, syndactyly, polydactyly, etc.), auditory defi-

cit, and characteristic facial dysmorphism.
This is a very rare syndrome (only around 30 In this section, we are presenting a type 1 oto-
cases recorded), two types of which are described: palatodigital syndrome with marked dysmor-
type 1 and type 2. This genetic disease results phism associated with hypertelorism, a protruding
from mutations in the FLNA gene associated with supra orbital ridge, a small flat nose, and palpe-
skeletal dysplasia (curved long bones, limb bral fissures oriented downward and outward
anomalies, including fan-shaped toes, bent fin- (Figs. 4.65 and 4.66).
Fig. 4.65 Otopalatodigital syndrome: profile
4.6 Lower Face Pathologies 123
Fig. 4.66 Otopalatodigital syndrome: rendered image and post-natal appearance
Francheschetti syndrome or Treacher

4.6 Lower Face Pathologies Collins syndrome
–– Associated: Acrofacial dysostosis
4.6.1 Otomandibular Dysplasias Nager or Miller Syndroms with limb
anomalies.
These pathologies combine external ear anom- • Unilateral or asymmetric forms
alies that are often warning signs (Figs. 4.67 –– Isolated
and 4.68), lower face anomalies at the mandib- First arch syndrome or first and second
ular level and mid-face anomalies at the malar arches syndrome
level. Hemifacial microsomy
We can divide otomandibular dysplasias into –– Associated: Goldenhar syndrome
two groups:
The facial dysmorphism that these syndromes
• Symmetric bilateral forms share is in external ear anomalies, with preauric-
–– Isolated: ular tags (or fibrochondromas (Fig. 4.67), auricu-
Mandibulofacial dysostosis lar anomalies (Fig. 4.68).
124 4 Dysmorphism
a b
Fig. 4.67 (a, b) Francheschetti or Treacher-Collins syndrome
4.6.1.1 Francheschetti or Treacher-

Collins Syndrome
Incidence is estimated at 1/50,000. The major
markers of this syndrome other than ear anom-
alies (auricular deformities, preauricular
tags, internal ear anomalies) include facial
bone anomalies: hypoplastic malar bones,
absent zygomatic arches, mandibles that lose
their usual angulation between the ramus and
the horizontal branch, impacting the temporo-
mandibular joint that can lead to serious limi-
tations in buccal opening (Figs. 4.70, 4.71,
and 4.72), micrognathia leading to a decrease
in the lower facial angle measurement
(Figs. 4.73 and 4.74).
Malar hypoplasia results in palpebral fissures
oriented downward and outward (Fig. 4.69), and
Fig. 4.68 Francheschetti syndrome: auricular anomalies
coloboma of the lower eyelids is frequent 40 % of cases, 60 % of cases being a de novo

between the external and middle thirds. mutation. The genetic origin corresponds to a
There can be cleft palate (Fig. 4.75). mutation at 5q32 encoding a protein called
This syndrome can express differently within “Treacle,” which is essential for the survival of
a same family. Family history can be found in neural crest cells.
Fig. 4.69 Treacher-Collins syndrome: malar hypoplasia and palpebral fissures oriented downward and outward
Fig. 4.70 Treacher-Collins syndrome: dotted line: unangulated mandible, dotted arrows: absence of zygomatic arch,
full-line arrow: malar hypoplasia
126 4 Dysmorphism
Fig. 4.71 Francheschetti syndrome: unangulated

mandible, interruptions of zygomatic arch
Fig. 4.72 Francheschetti syndrome: bone scan: malar hypoplasia, interrupted zygomatic arch, unangulated mandible
Fig. 4.73 Treacher-Collins syndrome: multiplanar view

128 4 Dysmorphism
Fig. 4.74 Treacher-Collins syndrome: micrognathia, lower facial angle: 45°
Fig. 4.75 Francheschetti syndrome: cleft palate (second-

ary palate)
4.6.1.2 Goldenhar Syndrome • Limbal dermoids

This syndrome is part of the oculo-auriculo-
vertebral spectrum of diseases, with an estimated The etiology of this syndrome remains
incidence of 1/6000. unclear.
Facial dysmorphism in this syndrome includes The differential diagnosis for the oculo-
external ear anomalies (fibrochondromas, auricu- auriculo-vertebral spectrum is the branchio-oto-
lar anomalies) (Fig. 4.76). renal syndrome (BOR syndrome, Fig. 4.79)
which associates facial markers with renal anom-
• Facial asymmetry impacts the mandible, the soft alies and family history. It is an autosomal domi-
parts of the cheeks, and edges of the mouth, cre- nant syndrome linked to a mutation of the EYA1
ating a lateral cleft that leads to an appearance of gene located on chromosome 8.
macrostomia (Figs. 4.77 and 4.78).
• There are related vertebra malformations (cer-
vical vertebra fusion, hemi-vertebra, etc.)
Fig. 4.76 Goldenhar syndrome: unilateral anomaly of the left ear, prenatal ultrasound and post-natal image
130 4 Dysmorphism
Fig. 4.77 Goldenhar syndrome, TUI, mouth asymmetry (yellow arrows)
a b
Fig. 4.78 Goldenhar syndrome mouth asymmetry. (a) prenatal, (b) post-natal
Fig. 4.79 BOR Syndrome: ear anomalies, facial symmetry, normal zygomatic arch and mandibles
4.6.2 Beckwith-Wiedemann The major risks linked to this syndrome are

Syndrome the development of tumors during the first 5 years
of life (Wilms tumor or nephroblastoma, hepato-
The incidence of this syndrome is estimated at blastoma, corticoadrenaloma, neuroblastoma,
1/13,000. It is a syndrome that results in exces- rhabdomyosarcoma). This risk is estimated at
sive growth. The three major classic markers are between 7.5 % and 10 %. The genetics of this
macrosomia, macroglossia (Figs. 4.80, 4.81, and syndrome are complex, but recent progress has
4.82), and abnormal openings in the anterior made it possible to better target children with
abdominal wall, especially an omphalocele tumor risk.
(Fig. 4.83). The minor markers are visceromeg- Facial dysmorphism is primarily marked by
aly (particularly the kidneys, liver, spleen and macroglossia, with a tongue that is constantly
pancreas, Fig. 4.84), ear anomalies (Fig. 4.85), sticking out (Figs. 4.80 and 4.81), the lingual
neonatal hypoglycemia, mesenchymal dysplasia perimeter is greater than normal (normal: gesta-
of the placenta in 20 % of cases (Fig. 4.86). tional age in weeks since last menstrual period X
A diagnosis of Beckwith-Wiedemann is 2.75, according to D. Nyberg Fig. 4.82), subtle
accepted when two major markers and one minor auricular anomalies that look like notches and
marker have been found. anomalies in the shape of the anthelix (Fig. 4.85).
132 4 Dysmorphism
Fig. 4.80 (a) Beckwith-Widermann syndrome: macroglossia. (b) Beckwith-Wiedemann syndrome: macroglossia
Fig. 4.81 Beckwith-Wiedemann syndrome: multiplanar image
Fig. 4.82 Beckwith-Wiedemann syndrome: lingual

perimeter
134 4 Dysmorphism
Fig. 4.83 Beckwith-

a
Wiedemann syndrome:
omphalocele
Fig. 4.84 Beckwith-Wiedemann syndrome: nephromegaly
Fig. 4.85 Beckwith-

Wiedemann syndrome: on
the right, control ear, on
the left, ear of affected
patient, with dotted line
indicated the anthelix
anomaly and the full arrow
the auricular notch
Fig. 4.86 Beckwith-Wiedemann syndrome: Mensenchymal dysplasia of the placenta, on ultrasound and fetal pathol-
ogy examination
4.6.3 Fetal Alcohol Syndrome orbits, with late intellectual development and
behavioral anomalies.
The effects of alcohol exposure on the fetus have • Facial dysmorphism recognizable on ultra-
been known for several decades and are grouped sound, combining short lower face, slight
together under the term “Fetal Alcohol Syndrome retrognathia, a long domed philtrum, and a
(FAS)”. The criteria defined in 1989 to diagnose thin upper lip (Figs. 4.87, 4.88, 4.89, and
it are an association of markers: 4.90).
• Prenatal and post-natal growth deficiency Revealing a context of fetal alcohol syndrome
• Microcephaly, biometric anomalies in the is often difficult and follow-up should be done
brain, in particular in the frontal lobes and the with tact.
136 4 Dysmorphism
Fig. 4.87 FAS: multiplanar image
Fig. 4.88 FAS:

practically normal
inferior facial angle,
long philtrum, short
height of lower face
Fig. 4.89 FAS: surface rendering

138 4 Dysmorphism
Fig. 4.90 FAS: post-natal appearance
4.7 Multiple-Level Pathologies Fig. 4.92), radial, cubital and ptergium

anomalies.
4.7.1 Cornelia de Lange Syndrome • Facial dysmorphism is characterized by retrog-
nathia that is more or less marked (Fig. 4.93),
This syndrome was described for the first time by anteverted nares (Fig. 4.94), round nose,
Mrs. Cornelia de Lange in 1933. It has an esti- marked nasal bridge (Fig. 4.93), thin upper lip
mated incidence of 1/45,000 to 1/62,500. It is (Fig. 4.93), domed philtrum (Fig. 4.94), down-
often accompanied by severe mental retardation. turned corners of the mouth (Fig. 4.7), and
Prenatal genetic diagnosis is difficult, which short mandible (Fig. 4.98).
means that the diagnosing ultrasonography must
know the markers well in order to analyze the Discovery of all or any part of this trio of
dysmorphism and pinpoint cardinal markers and markers requires one to look for more subtle yet
particularly evocative markers. quite suggestive markers:
It should be noted that enlarged nuchal trans-
lucency could be seen in the first trimester. The • Hypertrichosis (Fig. 4.99), with very long
classic ultrasound trio associates intrauterine eyelashes (Fig. 4.100).
growth retardation, limb defects and facial • A very small first metacarpal, which appears
dysmorphism. round (Fig. 4.101).
• The presence of a bony spine under the man-
• Growth retardation appears as early as the sec- dible (Fig. 4.102).
ond trimester, with its intensity seeming to
correlate with the severity of mental The genetics of this syndrome are complex: its
retardation. expression is variable, it is most frequently trans-
• Limb anomalies are variable. The most com- mitted sporadically, although a few cases of auto-
mon are oligodactyly, ectrodactyly (Fig. 4.91), somal dominant family transmission have been
phocomelia (characteristic if present, described.
4.7 Multiple-Level Pathologies 139
Mutations on three genes involved in chromo- Cornelia de Lange Syndrome linked to the X,
some cohesion (cohesion complex) are involved and the SMC3 gene (10q25).
in this syndrome.
The NIPBL and SMC1A genes are involved in
• Major form: the NIPBL gene (5p13.2) is 65 % of cases. If this mutation is identified, a pre-
mutated in approximately 50 % of patients. natal diagnosis can be suggested.
• Minor form: the SMC1A gene (SMC1L1,
Wp11.22-p11.21) is associated with a form of
Fig. 4.91 Cornelia de

Lange Syndrome:
oligodactyly
Fig. 4.92 Cornelia de Lange

Syndrome: phocomelia
140 4 Dysmorphism
Fig. 4.93 Cornelia de Lange syndrome: retrognathia
Fig. 4.95 Cornelia de Lange syndrome, 17 GW: ante-

verted nostrils, round nose
Fig. 4.94 Cornelia de Lange syndrome, 17 GW: marked

nasal bridge, domed philtrum
Fig. 4.96 Cornelia de Lange syndrome, 17 GW: thin

upper lip
Fig. 4.98 Cornelia de Lange syndrome: short mandible
Fig. 4.97 Cornelia de Lange syndrome: downturned cor-

ners of the mouth
Fig. 4.99 Cornelia de Lange syndrome: hypertrichosis

142 4 Dysmorphism
Fig. 4.100 Cornelia de Lange syndrome, 29 GW: very

long eyelashes
Fig. 4.102 Cornelia de Lange syndrome, 29 GW: bony

spine under the mandible (yellow arrow)
Fig. 4.101 Cornelia de Lange syndrome, 29 GW: round

first metacarpal (green arrow)
Fig. 4.104 Cornelia de Lange syndrome: post-natal

appearance
Fig. 4.103 Cornelia de Lange syndrome, 29 GW

144 4 Dysmorphism
4.7.2 Williams-Beuren Syndrome philtrum, and a wide mouth with an everted

lower lip, giving an “elfin” appearance
Williams-Beauren syndrome was first described (Figs. 4.105, 4.107 and 4.108).
in 1961 and 1962 by J.C.P. Williams, who
described the supravalvular aortic stenosis and Progress in cytogenetics, and in particular
A.J. Beuren who pinpointed the association with techniques that enable targeted testing for lost
intellectual disabilities. genetic material that corresponds to muta-
Today, this syndrome is still diagnosed during tions known to be responsible for syndromes
young childhood based on associated difficulties associated with mental retardation, has led
in school: ultrasonographers to develop precise studies
of subtle markers visible on ultrasound and to
• Mental retardation (IQ < 60) study in an objective manner dysmorphic
• Cognitive deficiencies: disturbed perceptual anomalies that had previously gone unseen.
functions in discord with proper language Williams-Beuren syndrome is a typical exam-
acquisition. ple benefiting from these advancements: the
• Supravalvular aortic stenosis heart disease (in dysmorphism is, indeed, analyzable on prena-
around 70 % of cases) or peripheral pulmo- tal ultrasound and the subravalvular aortic
nary stenosis. stenosis can also be recognized (Figs. 4.106,
• Facial dysmorphism that combines a broad 4.107, and 4.108).
forehead, malar hypoplasia, full cheeks, long
Fig. 4.105 Williams-Beuren syndrome, 30GW: small round nose, wide mouth with everted lower lip
Fig. 4.106 Williams-

Beuren syndrome,
30GW: supravalvular
aortic stenosis (pink
arrows, aortic valves;
yellow arrows, stenosis)
146 4 Dysmorphism
Fig. 4.107 Williams-Beuren syndrome, 30GW: HD

Live surface rendering
Fig. 4.108 Williams-Beuren syndrome, 30GW: fetopathological appearance. Left and central images show facial dys-
morphism, while the right image shows the aortic stenosis
4.8 A Few Additional Syndromes 147
4.8 A Few Additional Syndromes Incidence is 1/8500 to 1/12,000, with muta-

tions on the CDH7 gene being responsible in
4.8.1 CHARGE Association 75 % of cases.
Discovery of a heart defect associated with
It may seem odd in a book focused on the fetal an anomaly of the posterior fossa (vermian
face to discuss the CHARGE association of birth hypoplasia Fig. 4.110) should lead to a search
defects, yet the presence of external ear and eye for dysmorphism such as auricular anomalies
anomalies fit in the framework of facial dysmor- (they are often small with a rather rectilinear
phism and we considered that pertinent enough upper edge (Fig. 4.111), microphthalmia
to include this association in this chapter. (Fig. 4.112), colomba (Fig. 4.110). All cases
The acronym CHARGE stands for a set of present arhinencephaly (Figs. 4.113 and 4.114)
birth defects combining Coloboma of the eye and anomalies of the semicircular canals—
(Fig. 4.109), Heart defects (tetralogy of Fallot, hypoplasia or more frequently agenesis
double outlet ventricle, atrioventricular canal (Fig. 4.115). One can use ultrasound to look for
defect, etc.), Atresia of the choanae, Retardation these two latter anomalies, and then confirm
of growth and/or development, Genital hypopla- with MRI.
sia, and Ear abnormalities.
Fig. 4.109 CHARGE association: coloboma of the ret-

ina (virtual fundus exam technique)
148 4 Dysmorphism
Fig. 4.110 CHARGE association: vermian anomaly (defect in lower region)
Fig. 4.111 CHARGE association: ear anomalies

150 4 Dysmorphism
Fig. 4.112 CHARGE

association:
microphthalmia
a b
c d
Fig. 4.113 CHARGE association: (a). olfactive grooves present on ultrasound; (b) absence of grooves (CHARGE),
(c) bulbs present on MRI, (d) absence of bulbs (CHARGE)
152 4 Dysmorphism
Fig. 4.114 CHARGE association: fetopathological

appearance of arhinencephaly (olfactive bulbs are not
visible, arrows)
a b
c d
Fig. 4.115 CHARGE association: (a) normal semicircular canals (SCC), (b) very hypoplastic SCC in case of
CHARGE, (c). absence of SCC (RX CHARGE), (d). fetopathological image, absence of SCC
154 4 Dysmorphism
4.8.2 Noonan Syndrome rotating helix (Figs. 4.118, 4.119, and 4.120),
and a short, thick neck (Fig. 4.123).
This syndrome has an estimated incidence of
between 1/1000 and 1/2500. This diagnosis should This syndrome is inherited in an autosomal
be considered when a fetus presents increased dominant pattern. For half the patients, there is a
nuchal translucency thickness (especially if persis- missense mutation in gene PTPN11 localized on
tent, Fig. 4.115) with a normal karyotype, but also chromosome 12 leading to a gain in phsophoty-
if a fetus presents hydamnios, pleural effusion or rosine function. Other genes involved have
edemas if not ordinary cause can be found. recently been uncovered.
The characteristics of this syndrome are: This chapter highlights the progress that has
been made in the prenatal study of fetal dysmor-
• Cardiovascular anomalies: pulmonary steno- phism thanks to the innumerable technical
sis, hypertrophic cardiomyopathy advances that have been made not only in imag-
• Scoliosis-like vertebral anomalies ery, but also in genetic medicine, cytogenetics
• Umbilical vein anomalies such as persistent and molecular genetics.
right umbilical vein Working in a pluridisciplinary team allows the
• Cryptorchidism ultrasonographer to develop his or her knowledge
• Facial dysmorphism associated with hyper- and to sharpen his or her curiosity looking for
telorism (Fig. 4.116), downwardly slanting pal- markers that may be subtle but that are present.
pebral fissures (Fig. 4.119), a deep vertical This work must be accompanied with an
groove in the middle of the philtrum (Figs. 4.121 extremely rigorous methodology, as I hope we
and 4.122), low-set ears with a thick, b ackward have demonstrated.
Fig. 4.116 Noonan syndrome: multiplanar view, hypertelorism
Fig. 4.117 Noonan syndrome: evolution of neck thickness

156 4 Dysmorphism
Fig. 4.119 Noonan syndrome: ears at 23GW and

postnatal
Fig. 4.118 Noonan syndrome: ears 23GW, poorly
folded, low-set and rotated backward
Fig. 4.120 Noonan syndrome, 28GW: dysmorphism, hypertelorism, downward slanting palpebral fissures
Fig. 4.123 Noonan syndrome: postnatal, thick neck
Fig. 4.121 Noonan syndrome, 23GW: Deep grooves in

Cupid’s arc
Fig. 4.122 Noonan syndrome: 21 SA: other deep grooves

in Cupid’s arc
158 4 Dysmorphism
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Facial Tumors
5
Facial tumors can affect various aspects of the tumors originate at the base of the fetal skull
face that are most often linked to their anatomo- and reach the hard palate and the sphenoid.
pathological origin. They develop rapidly towards the exterior of
In this chapter, we do not attempt to be exhaus- the mouth and the nasal cavities, and their
tive, but our objective is to describe a few exam- extension can be major and impressive, some-
ples of the tumors seen most frequently in times masking the entire fetal face (Figs. 5.1,
prenatal examinations. 5.2, and 5.3). Sometimes they are more limited
(Fig. 5.4).
The appearance of these tumors is most often
5.1 Teratomas mixed and disorganized, associating solid and
liquid components in variable quantity, without
These tumors, also called “epignathus”, have systematic vascularization.
an incidence estimated at between 1/35,000 and Sometimes these teratomas have a cervical
1/200,000 live births. The majority of these starting point (Fig. 5.5).

164 5 Facial Tumors
Fig. 5.1 Giant epignathus (arrows: ocular structures)
Fig. 5.3 Giant epignathus: post-natal appearance
Fig. 5.2 Giant epignathus: HD live rendering highlight-

ing the heterogeneous aspect of the tumor
5.1 Teratomas 165
Fig. 5.4 Small facial teratoma outside of one

nostril
Fig. 5.5 Cervical teratoma: heterogenous aspect, vascularization
166 5 Facial Tumors
5.2 Hemangiomas The aspect is most often echogenic, usually

homogenous, although sometimes heterogeneous
Vascular anomalies of the face can be divided (Fig. 5.7). The Doppler highlights hypervascular-
into vascular malformations and vascular tumors. ization at the level of the tumor (Figs. 5.6 and
The most frequent kind of vascular tumor is the 5.7). The opposite bone base could be the seat of
hemangioma. These are further divided into those a slight depression related to the subperiostal
that spontaneously disappear (regression is usu- process origin (Fig. 5.8).
ally complete by the age of 14 months) and those
for which involution is not spontaneous.
Fig. 5.6 Frontal hemangioma: left, rendered aspect, right vascularization and slight bone depression
5.2 Hemangiomas 167
Fig. 5.7 Extraorbital hemangioma: slightly heterogeneous tumor aspect and vascularization
Fig. 5.8 Left extraorbital hemangioma in HD live

rendered mode
168 5 Facial Tumors
5.3 Lymphangiomas larly from an esthetic point of view. Their appear-

ance on the ultrasound is that of a multicystic
Frequently found at the cervical level, they are formations (the cysts can be of variable sizes
much less frequent on the face. Surgery is very Figs. 5.9, 5.10, 5.11, 5.12 and 5.13).
difficult and could leave major damage, particu-
Fig. 5.9 Cystic

lymphangioma of the
upper lip: left, cystic
aspect of the tumor; right,
rendered mode
Fig. 5.10 Cystic lymphangioma of the upper lip: TUI mode

5.3 Lymphangiomas 169
Fig. 5.11 Cystic lymphangioma of the upper lip: classic rendering and HD live (lower image)
170 5 Facial Tumors
Fig. 5.12 Lymphangioma of the upper lip

(post-natal appearance)
5.4 Expansive Process of Brain Tumors 171
5.4 xpansive Process of Brain

E The histological nature of these tumors is variable.
Tumors We will illustrate with a cerebral hamartoma that
spread, destroying the left orbit and invading the
Brain tumors can develop to be big and “fuse” mouth (Figs. 5.13, 5.14, 5.15, and 5.16).
through the skull bone structures such as the orbits.
Fig. 5.13 Cerebral

hamartoma: medio-
cerebral origin
172 5 Facial Tumors
Fig. 5.14 Cerebral hamartoma: TUI extension of tumor into the orbit and mouth
Fig. 5.15 MRE of cerebral hamartoma

5.5 Pai Syndrome 173
Fig. 5.16 Cerebral hamartoma: destruction of the orbit by the tumor (maximum mode)
5.5 Pai Syndrome fetal face and the secondary hard palate
(Fig. 5.17).
This rare syndrome is characterized by the asso- The few examples found in this chapter illus-
ciation of pericallosal lipomas, median cleft of trate the difficulty of delivering a precise etio-
the palate and upper lip, and by the presence of logical diagnosis and highlight the importance of
skin polyps on the face. It can include bifid nose. pluridisciplinary work to best counsel couples
Psychomotor development is normal. facing these difficult situations.
The discovery of a callous lipoma should, evi-
dently, lead to the attentive examination of the
174 5 Facial Tumors
Fig. 5.17 PAI syndrome in rendered mode: multiple skin polyps, bifid nose, median cleft
References I. Antenatal sonographic and magnetic resonance

images of a giant hemangioma of the fetal skull.
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A. Prenatal diagnosis of an epignathus: a case report Ultrasound Obstet Gynecol. 1999;14(6):407–18.
and review of the literature. Ultrasound Obstet 8. Sahinoglu Z, Aktug Ertekin A, Cerrah Celayir A,
Gynecol. 2001;18(2):178–81. Gucluer B. Prenatal diagnosis of a huge facial tumor:
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K, Nakamura T, Kondoh Y, Noguchi M, Konishi Ultrasound Obstet Gynecol. 2008;32(5):708–10.
The Eye
6
The study of the fetal eye is an important moment The retina and lens are irrigated by the hyaloid
in the examination of the face as numerous ocular artery (a branch of the ophthalmic artery) which
anomalies are often found in syndromic disor- reaches into the ocular globe by the coloboma fis-
ders. Precise knowledge of the of normal semei- sure located on the ventral side of the optic pedi-
ology is essential to better understand pathological cle. If this fissure does not close, there will be
aspects. coloboma anomalies.
6.1 Embryology Review 6.1.1 Ultrasound of a Normal Eye
Beginning on the 21st day (of pregnancy), neural 6.1.1.1 First Trimester
folds in the diencephaly region invaginate to The ocular structures are visible as early as the
form gutters that transform into optic vesicles, first trimester, in particular the ocular globes, the
which then rapidly invaginate again into optic lens and the orbits. Note that at 13GW, it is pos-
cups. The ectoderm in contact with the vesicle sible to visualize a slight posterior thickening of
thickens to constitute the lens placode, which in the lens that corresponds to remnants of the prim-
turn invaginations to become the lens vesicle. itive vitreous (Fig. 6.1).
This then transforms into the lens.

176 6 The Eye
6.1.1.2 Second Trimester quite visible; the hyaloid artery appears as a thin
The orbits are perfectly identifiable: in particular line connection the back side of the lens to the
in maximum volume mode, which makes it pos- retina (it does not persist beyond 28GW)
sible to see the various bone components (Fig. 6.3).
(Fig. 6.2). The ocular globes and the lenses are
Fig. 6.1 The eye during the first trimester
Fig. 6.2 Bony orbits

(maximum volume
mode)
6.1 Embryology Review 177
Fig. 6.3 Eye at 22 GW (note the presence of hyaloid Fig. 6.5 Pupil on a frontal view
arteries) Pupil
in 2006 and the biometrics in 2007 in the journal

Ultrasound in Obstetrics and Gynecology (cf.
references) (Figs. 6.7, 6.8, and 6.9).
The eyelids and eyelashes are visible from the
second trimester (Fig. 6.10).
It is possible to evaluator the fundus (virtual)
using volumetric capture using the technique that
we described in 2008 in the journal Ultrasounds
in Obstetrics and Gynecology (cf. References)
(Figs. 6.11 and 6.12).
It is possible to measure the inter-orbital dis-
tance. In France, we tend to use the measurement
Fig. 6.4 Eye during the third trimester from the middle of one orbit to the middle of the
Cornea other (Fig. 6.13), the relationship between the
Pupil IOD/BPD is constant: 0.47 at 22 GW and 0.42 at
Front chamber
Vitreous body
32 GW.
Lens A simple technique is that of the “virtual
orbit”: if the two eyes are separated a normal dis-
tance, it is possible to put just one “virtual orbit”
6.1.1.3 Third Trimester in between the two normal orbits (Fig. 6.14).
The various eye structures are perfectly visible, When making a diagnostic study, one will use
as seen in Fig. 6.4, with the pupil being visible on various published tables, in particular those
a frontal view (Fig. 6.5). regarding measurements regarding the orbits, the
Furthermore, one can see the optic nerve, the ocular globes and the lenses.
ophthalmic artery, the retrobulbar fat (which In addition, an attentive study will make it
appears as clearly echogenic) (Fig. 6.6). possible to visualize ocular movements. It should
The chiasma opticum can be seen from 20GW be noted that strabismus, particularly when diver-
using the volume mode. We described the capture gent, is often observed in the fetus.
178 6 The Eye
Fig. 6.6 Optic nerve, ophthalmic artery, retrobulbar fat

Optic nerve
Ophthalmic artery
Retrobulbar fat
Fig. 6.7 Chiasma

opticum at 22, 28, 32
and 34 GW
Fig. 6.8 Chiasma opticum at 22 GW:

fetopathological examination (* olfactive bulbs,
° chiasma, Sph sphenoid wings)
Fig. 6.9 Chiasma 3.8

biometrics 3.6
3.4
3.2
3.0
2.8
FOC (mm)
2.6
2.4
2.2
2.0
1.8
1.6
1.4
3rd and 97th
1.2
5th and 95th
20 22 24 26 28 30 32 34 36
GA (weeks) 50th
Fig. 6.10 Eyelids and eyelashes (yellow arrow)
180 6 The Eye
Fig. 6.11 Capturing the eye fundus

Fig. 6.12 Fundus at 16 GW (note the slight depression corresponding to the insertion of the hyaloid artery) at 25 GW
and 36 GW
182 6 The Eye
Fig. 6.13 Interorbital distance measurement

IOD
Fig. 6.14 Virtual orbit
6.1.2 ain Aspects of Ocular

M cyst appears as an anechogenic formation inside
Pathologies and to the front of the eye. It is sometimes possi-
ble to reveal a small lithiathis in the cyst
6.1.2.1 Dacryocystocele (Fig. 6.15). In the majority of cases, these dac-
This is a cyst in the lachrymal canal that can be ryocystoceles are easily resolvent after birth or
seen on an ultrasound as a small swelling in the even in utero (Fig. 6.16).
internal corner of the eye. On an axial view, this
Fig. 6.15 Dacryocystoceles (white arrow: lithiathis, black arrow: volumetric aspect)
184 6 The Eye
Fig. 6.16 Dacryocystoceles: pre and post natal
Fig. 6.17 Hypotelorism

related to semi-lobar
holoprosencephaly. BPD/
OFD: 0.40 for 29 GW
6.1.2.2 Hypoltelorism, Cyclopia ultrasound was not carried out during the first tri-
If hypotelorism is brought to light, it is impera- mester (Fig. 6.19). These cyclopias can present
tive to look for holoprosencephaly, as illustrated with one or two lenses, the front bones are fused,
in the below example (Fig. 6.17). and the metopic suture is not visible. These
Extreme forms of hypotelerism result in anomalies are most often seen as part of lobar
cyclopia that can be seen as early as the first tri- holoprosencephaly, and in particular in trisomy
mester (Fig. 6.18). Sometimes, the aspect is 13-type anomalies (Fig. 6.19).
found in the second trimester, in particular if an
Fig. 6.18 Cyclopia in the first trimester: upper right, alobar holoprosencephaly (arrow); lower left: to lenses (arrow);
right: volumetric rendered image (proboscis, single orbit, nose not visible)
Fig. 6.19 Cyclopia in the second trimester: left, rendered volumetric image; lower right, single lens; lower left: fusion
of frontal bones, no visible metopic suture
186 6 The Eye
6.1.2.3 Cataracts ter (Fig. 6.20), or during the morphological

The lens is opaque, appearing echogenic. This examination done during the second trimester
aspect could be visible as early as the first trimes- (Fig. 6.21).
Fig. 6.20 Cataract during

the first trimester
Fig. 6.21 Cataract during the second trimester

6.1.2.4 Microphthalmias from the front, and then the volume is visualized
Microphthalmias can involve one eyeball from behind the facial mass, looking for internal
(Figs. 6.22, 6.23, or 6.24) or be bilateral orbital contours (Fig. 6.26). This technical pos-
(Figs. 6.28 and 6.29). sibility can be assimilated to the reverse view
The size of the eyes can have a very minimal technique described by S. Campbell to visualize
difference, which means it is indispensable to palatal defects.
refer to measurement tables (Goldstein 1998 A colobomatous origin is frequent in microph-
OUG). And MRI can be complementary to ultra- thalmia, so one should be particularly attentive to
sound imagery (Fig. 6.25). looking for a retinal defect (Fig. 6.27).
It is possible to use the reverse view technique.
The volumetric image of the fetal face is captured
Fig. 6.22 Microphthalmia at 22 GW
188 6 The Eye
Fig. 6.23 Unilateral microphthalmia at 30 GW (blue arrow: persistence of primitive vitreous)
Fig. 6.24 Unilateral microphthalmia: prenatal rendered image and post-natal appearance
Fig. 6.25 Unilateral

microphthalmia: MRI
Fig. 6.26 Unilateral microphthalmia – reverse view: right, capture from the front; left: view of the facial mass from
behind (not the small size of the left orbit, which is hard to visualizes from behind)
190 6 The Eye
Fig. 6.27 Unilateral colobomatous microphthalmia (arrow: defect)
Fig. 6.28 Bilateral microphthalmia

Fig. 6.29 Bilateral colobomatous microphthalmia

(arrow: colobomatous cyst)
Fig. 6.30 Bilateral anophthalmia
6.1.2.5 Anophthalmia Remember that to confirm there is an eye in an

Unilateral or bilateral: no orbital relief and not orbit, one needs to visualize the ocular structures.
ocular structures are visible (Fig. 6.30). Normally, it is easiest to visualize the lenses.
192 6 The Eye
6.1.2.6 Buphthalmia globe is too large, creating an impression of

This should not be confused with exophthalmia: exophthalmia. Biometrics will help to determine
the bony orbit is normal sized, but the ocular the diagnosis (Fig. 6.31).
Fig. 6.31 Bilateral buphthalmia

6.1.2.7 Exophthalmia cannot contain the ocular globe, leading to its

Unlike buphthalmia, the ocular globe is normal exteriorization (Fig. 6.32).
sized, but the orbit is too small or deformed and
Fig. 6.32 Exophthalmia in a case of craniostenosis (the scanner clearly shows orbital asymmetry)
194 6 The Eye
6.1.2.8 Persistent Primary Vitreous Buphthalmia, persistent primary vitreous

This arises from the persistence of embryonic (Fig. 6.35) and retinal dysplasia (Fig. 6.34) are
structures: the primary vitreous and the hyaloid often present in Walker-Warburg syndrome, with
vessels. type 2 lissencephaly, associating, in particular,
On an ultrasound, it can be seen by the present cerebral gyration, hydrocephaly, and a
of an echogenic structure behind the lens. Most “Z”-shaped cerebral trunk.
often the aspect is an arc of a circle or triangular (See the chapter on cerebral gyration troubles
with a posterior point. This persistence often in the “Normal and Pathological Fetal Brain” by
accompanies microphthalmia (Figs. 6.23 and 6.33). the same publisher).
Fig. 6.33 Persistence of primary vitreous and

microphthalmia
Fig. 6.34 Retinal dysplasia: Walker-Warburg syndrome

6.1
Embryology Review
Fig. 6.35 Persistent primary vitreous and buphthalmia – Walker-Warburg syndrome
195
196 6 The Eye
Fig. 6.36 Peters syndrome: glaucoma and cataract
6.1.2.9 Peters Syndrome Measurement of the posterior branches of the

This syndrome is linked to an anomaly in the chiasma can currently be considered as a major
anterior eye chamber related to an anomaly in prognostic element.
embryologic development that leads to glaucoma In a series that we recently published in ultra-
and opacification of the central part of the cornea sound, the only two children who were affected
(Fig. 6.36). This is a recessive autosomal anom- by a septo-optic dysplasia had posterior chias-
aly. It can be associated with facial dysmorphism matic branches presenting measurements very
and hypospadias. much below what was expected. Fig. 6.36 illus-
trates a case of serious hypoplasia of the posterior
6.1.2.10 Septal and Chiasma Agenesis branches of the chiasma at 31 GW, in a fetus who
When encountering a septel agenesis, the prob- will be affected by total blindness (Z-score: −5)
lem when it comes to advising the couple, is (Fig. 6.37).
whether or not there is a septo-optical dysplasia, Several anomalies can be discovered in the
with is terrible consequences, which are endo- eyes, including excessively long eyelids in
crine troubles and blindness. Cornelia de Lange syndrome (see chapter on dys-
C. Lépinard and his team in Angers focused morphism), cryptophthalmia in Frazer syndrome,
their research on measuring maternal plasma and more.
oestriol. When the rate collapses, there is a dys- As a result, the serious and complete examina-
function of the hypothalamo-hypophyseal axis tion of the fetus cannot neglect and attentive and
in the fetus. detailed examination of the fetal eyes.
References 197
Fig. 6.37 Hypoplasia of the posterior branches of the chiasma in volumetric mode and MRI
retina with 3D ultrasound. Ultrasound Obstet

References Gynecol. 2008;32(3):410.
9. Pietryga M, Karolczak-Kulesza M, Jankowiak A,
1. Spaggiari E, Vuillard E, Baumann C, Dupont C, Brazert J, Kociecki J. Prenatal diagnosis of eye abnor-
Belarbi N, Oury JF, Delezoide AL, Guimiot malities. Ultrasound Obstet Gynecol. 2007;30(4):421.
F. Ultrasound detection of hyaloid artery in the third 10. Wenling S, Manhua C, Zongxiang L, Hui L,
trimester of pregnancy: a pathological finding. Zongxiang L. Prenatal diagnosis of dacrocystocele.
Ultrasound Obstet Gynecol. 2012;39(4):478–9. Ultrasound Obstet Gynecol. 2010;36(S1):239–40.
2. Bault JP. Visualisation of the fetal optic chiasm. 11. Wong HS, Parker S, Tait J, Pringle KC. Antenatal
Ultrasound Obstet Gynecol. 2006;28(4):433–4. diagnosis of anophthalmia by three-dimensional
3. Bault JP, Quarello E. Retinal coloboma: prenatal diagno- ultrasound: a novel application of the reverse face
sis using a new technique, the ‘virtual fetal eyeground’. view. Ultrasound Obstet Gynecol. 2008;32(1):103–5.
Ultrasound Obstet Gynecol. 2009;33(4):495–6. 12. Yazicioǧlu HF, Ocak Z. Walker–Warburg syndrome
4. Goldstein I, Tamir A, Zimmer EZ, Itskovitz-Eldor with persistent hyperplastic primary vitreous detected
J. Growth of the fetal orbit and lens in normal pregnan- by prenatal ultrasonography. Ultrasound Obstet
cies. Ultrasound Obstet Gynecol. 1998;12(3):175–9. Gynecol. 2010;35(2):247–9.
5. Horimoto N, Hepper PG, Shahidullah S, Koyanagi 13. Boog G, Le Vaillant C, Joubert M. Prenatal sono-
T. Fetal eye movements. Ultrasound Obstet Gynecol. graphic findings in Peters-plus syndrome. Ultrasound
1993;3(5):362–9. Obstet Gynecol. 2005;25(6):602–6.
6. Mashiach R, Vardimon D, Kaplan B, Shalev J, 14. Lepinard C, Coutant R, Boussion F, Loisel D,
Meizner I. Early sonographic detection of recurrent Delorme B, Biquard F, Bonneau D, Guichet A,
fetal eye anomalies. Ultrasound Obstet Gynecol. Descamps P. Prenatal diagnosis of absence of the sep-
2004;24(6):640–3. tum pellucidum associated with septo-optic dysplasia.
7. Bault JP. Prognos c value of fetal op c chiasm mea- Ultrasound Obstet Gynecol. 2005;25(1):73–5.
surements in fetuses with septal agenesis. Ultrasound 15. Bault JP, Salomon LJ, Guibaud L, Achiron
Obstet Gynecol. 2007;30(4):390. R. Management of fetuses with septal agenesis. A role
8. Bault JP. Re nal coloboma: a case report using “virtual for 3D US measurement of the fetal optoc tract.
eyeground”: a new technique to visualize the fetal Ultrasound Obstet Gynecol. 2011;37(5):570–5.
Biometric Parameters
7
7.1 The Eyes
Table 7.1 The fetal orbital diameter (mm)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 5.2 4.8–5.7 4.5 5.0 5.3 5.7 5.7
15 26 6.1 5.9–6.3 5.4 5.5 6.2 6.5 6.7
16 25 6.6 6.3–6.9 5.8 6.2 6.5 7.0 7.6
17–18 19 7.3 6.7–7.8 6.2 6.5 6.7 9.0 9.0
19–20 23 9.8 9.3–10.2 8.6 9.0 10.0 10.1 11.3
21 19 10.5 10.0–10.9 9.4 9.9 10.0 11.0 12.0
22 26 10.4 10.0–10.7 9.5 9.6 10.5 11.0 11.3
23 21 10.7 10.4–11.1 9.6 10.0 10.5 11.4 11.5
24 19 11.6 11.3–11.8 10.7 11.0 11.5 12.0 12.5
25 13 11.2 11.4–12.4 10.3 11.0 12.2 12.5 12.8
26 16 12.7 12.0–13.4 11.0 11.0 12.7 13.8 14.5
27 14 13.0 12.4–13.5 11.9 12.0 12.9 13.4 14.8
28 21 13.0 12.7–13.3 21.1 12.0 13.1 13.3 14.1
29 23 13.9 13.4–14.4 12.6 13.0 13.7 14.6 15.7
30–31 24 14.2 13.8–14.5 13.3 13.0 13.9 14.7 15.4
32–33 24 14.4 13.7–15.1 12.2 13.0 14.1 14.8 17.5
34–36 26 15.8 15.4–16.2 14.6 15.0 15.7 16.5 16.9
Growth of the fetal orbit and lens in normal pregnancies. Ultrasound in Obstetrics and Gynecology–Volume 12, issue 3,
December 2002, 175–179 I. Goldstein, A. Tamir, E.Z. Zimmer, J. Itskowitz-Eldor
GA gestational age, CI confidence interval

200 7 Biometric Parameters
Table 7.2 The fetal orbital circumference (mm)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 16.4 15.1–17.8 14.1 15 16.5 17.9 17.9
15 26 19.1 18.4–19.8 17.0 17 19.5 20.4 21.0
16 25 20.7 19.9–21.6 18.1 19 20.4 21.9 23.8
17–18 19 22.9 21.2–24.6 19.3 20 20.9 28.3 28.3
19–20 23 30.6 29.3–31.9 26.9 28 31.4 31.7 35.5
21 19 32.9 31.5–34.3 29.4 31 31.4 34.6 37.7
22 26 32.6 31.5–33.6 29.7 30 33.0 34.5 35.4
23 21 33.7 32.6–34.8 30.2 31 33.0 35.8 36.1
24 19 36.3 35.4–37.2 33.5 35 36.1 37.7 39.3
25 13 37.5 35.8–39.1 32.4 36 38.3 39.3 40.3
26 16 40.0 37.8–42.1 34.7 36 39.8 43.4 45.5
27 14 40.7 39.0–42.4 37.4 38 40.5 42.0 46.4
28 21 40.8 39.9–41.7 38.0 39 41.0 41.6 44.4
29 23 43.7 42.2–45.1 39.6 40 42.9 45.9 49.4
30–31 24 44.58 43.5–45.6 41.9 42 43.8 46.0 48.2
32–33 24 45.3 43.0–47.5 38.3 41 44.4 46.4 54.9
34–36 26 49.7 48.5–50.8 46.0 47 49.4 51.7 52.9
Growth of the fetal orbit and lens in normal pregnancies. Ultrasound in Obstetrics and Gynecology–Volume 12, issue
3, December 2002, 175–179 I. Goldstein, A. Tamir, E.Z. Zimmer, J. Itskowitz-Eldor
Table 7.3 The fetal orbital area (mm2)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 21.6 18.0–25.2 15.9 19.3 21.7 25.5 25.5
15 26 29.2 27.1–31.3 23.0 23.8 30.2 32.9 35.1
16 25 34.4 31.6–37.3 26.2 30.2 32.9 38.2 44.9
17–18 19 42.7 36.2–49.3 29.7 33.2 34.7 63.6 63.6
19–20 23 75.3 68.7–81.8 57.4 63.6 78.6 80.2 100.5
21 19 86.5 79.0–94.1 68.7 76.2 78.6 95.1 113.1
22 26 84.9 79.4–90.4 70.2 72.8 86.6 94.4 99.5
23 21 90.5 84.6–96.5 72.4 79.8 86.6 102.1 103.9
24 19 105.2 100.2–100.3 89.1 100.0 103.0 113.1 122.8
25 13 112.2 102.8–121.5 84.2 103.0 116.0 122.8 129.2
26 16 128.2 114.4–142.0 95.8 106.0 126.0 149.7 165.2
27 14 132.4 120.8–144.0 111.0 116.0 130.0 140.4 170.9
28 21 132.6 127.0–138.3 114.0 124.0 133.0 137.9 157.0
29 23 152.5 142.0–162.9 124.0 131.0 146.0 167.5 194.3
30–31 24 158.3 150.5–166.2 139.0 143.0 152.0 168.8 185.1
32–33 24 165.1 148.2–182.1 117.0 137.0 156.0 170.9 240.0
34–36 26 196.6 187.9–205.3 167.00 181.0 194.0 212.6 222.9
7.1 The Eyes 201
Table 7.4 Diameter of the fetal lense (mm)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 2.5 2.3–2.7 2.1 2.4 2.5 2.7 2.9
15 26 2.9 2.9–3.0 2.7 2.8 2.9 3.1 3.2
16 25 2.9 2.8–3.0 2.7 2.8 2.9 3.1 3.2
17–18 19 3.3 3.0–3.6 2.8 2.9 3.0 3.3 5.0
19–20 23 4.1 4.0–4.3 3.6 4.0 4.0 4.3 5.0
21 19 4.4 4.1–4.6 3.7 3.9 4.0 5.0 5.0
22 26 4.4 4.2–4.7 3.9 4.0 4.3 5.0 5.0
23 21 4.6 4.3–4.8 3.8 4.0 5.0 5.0 5.0
24 19 4.6 4.4–4.8 4.0 4.3 4.6 5.0 5.0
25 13 4.8 4.6–5.0 4.2 4.6 5.0 5.1 5.2
26 16 5.0 4.8–5.2 4.4 4.8 5.1 5.2 5.5
27 14 5.0 4.8–5.2 4.4 4.8 5.1 5.2 5.5
28 21 5.1 5.0–5.2 4.5 5.0 5.2 5.2 5.5
29 23 5.3 5.1–5.5 4.6 5.2 5.2 5.5 5.9
30–31 24 5.3 5.2–5.5 4.8 5.1 5.5 5.5 5.7
32–33 24 5.6 5.4–5.8 4.8 5.2 5.5 5.9 6.2
34–36 26 5.8 5.6–6.0 5.4 5.5 5.7 6.0 6.5
Table 7.5 Area of the fetal lens (mm2)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 5.1 4.3–6.9 3.5 4.4 4.9 5.6 6.6
15 26 6.8 6.4–7.2 5.9 6.2 6.6 7.6 8.0
16 25 6.7 6.3–7.0 5.6 6.2 6.6 7.3 8.0
17–18 19 8.8 6.9–10.8 7.9 9.0 9.0 10.6 13.8
19–20 23 13.6 12.4–14.8 10.2 12.0 12.6 14.5 19.6
21 19 15.1 13.3–17.0 10.8 12.0 12.6 19.6 19.6
22 26 15.8 14.2–17.3 12.2 12.0 14.2 19.6 19.6
23 21 16.6 15.0–18.2 11.6 12.0 19.6 19.6 19.6
24 19 16.9 15.5–18.4 12.6 14.0 16.6 19.6 19.6
25 13 18.3 16.7–19.9 13.6 16.0 19.6 20.4 21.2
26 16 19.7 18.2–21.3 15.2 18.0 19.6 21.2 23.8
27 14 19.8 18.1–21.4 15.2 18.0 19.6 21.2 23.4
28 21 20.5 19.4–21.7 15.9 19.0 21.2 21.2 23.8
29 23 22.3 20.6–24.0 16.4 21.0 21.2 23.8 27.4
30–31 24 22.4 21.1–23.8 18.1 20.0 23.8 23.8 25.9
32–33 24 24.5 22.8–26.3 18.1 21.0 23.8 27.4 30.0
34–36 26 26.6 25.0–28.1 23.0 23.0 25.6 28.3 33.5
Table 7.6 Circumference of the fetal lens (mm)

Centiles
GA (weeks) N Mean 95 % CI 10 25 50 75 90
14 10 8.0 7.3–8.6 6.7 7.5 7.9 8.4 9.1
15 26 9.2 9.0–9.5 8.6 8.8 9.1 9.7 10.1
16 25 9.1 8.9–9.4 8.4 8.8 9.1 9.6 10.0
17–18 19 11.0 9.3–11.4 9.5 10.0 11.0 11.5 12.5
19–20 23 13.0 12.4–13.6 11.3 12.0 12.6 13.5 15.7
21 19 13.7 12.8–14.5 11.6 12.0 12.6 15.7 15.7
22 26 14.0 13.3–14.7 12.4 12.0 13.4 15.7 15.7
23 21 14.4 13.7–15.1 12.1 12.0 15.7 15.7 15.7
24 19 14.5 13.9–15.2 12.6 130 14.5 15.7 15.7
25 13 15.1 14.5–15.8 13.1 14.0 15.7 16.0 16.3
26 16 15.7 15.1–16.3 13.8 15.0 15.7 16.3 17.3
27 14 15.7 15.1–16.4 13.8 15.0 15.9 16.3 17.1
28 21 16.3 15.6–16.5 14.1 15.0 16.3 16.3 17.3
29 23 16.7 16.1–17.3 14.3 16.0 16.3 17.3 18.5
30–31 24 16.7 16.2–17.2 15.1 16.0 17.3 17.3 18.0
32–33 24 17.5 16.9–18.1 15.1 16.0 17.3 18.5 19.4
34–36 26 18.2 17.7–18.8 17.0 17.0 17.9 18.9 20.5
7.3 Vitreous Circumference 203
Table 7.7 The outer orbital diameter (OOD) and inner 7.3 Vitreous Circumference
orbital diameter (IOD)
OOD (mm) IOD (mm) Measurement protocol
Centiles Centiles Coronal view: the transverse diameter and
GA (weeks) 5 50 95 5 50 95 the supero-inferior diameter of the vitreous
12 8 15 23 4 9 13 are measured from one internal edge to the
13 10 18 25 5 9 14 other. The circumference is calculated auto-
14 13 20 28 5 10 14 matically with a formula (D1 + D1) ×1.57
15 15 22 30 6 10 14
16 17 25 32 6 10 15
Table 7.9 Vitreous Circumference
17 19 27 34 6 11 15
18 22 29 37 7 11 16 Centiles
19 24 31 39 7 12 16 GA (weeks) 5 50 95
20 26 33 41 8 12 17 12 4 10.9 17.7
21 28 35 43 8 13 17 13 7.7 14.6 21.4
22 30 37 44 9 13 18 14 10.9 17.8 24.6
23 31 39 46 9 14 18 15 13.8 20.6 27.5
24 33 41 48 10 14 19 16 16.3 23.2 30.0
25 35 42 50 10 15 19 17 18.6 25.4 32.3
26 36 44 51 11 15 20 18 207 27.5 34.3
27 38 45 53 11 16 20 19 22.5 29.4 36.2
28 39 47 54 12 16 21 20 24.2 31.1 37.9
29 41 48 56 12 17 21 21 25.8 32.6 39.4
30 42 50 57 13 17 22 22 27.2 34.0 40.9
31 43 51 56 13 18 22 23 28.5 35.4 42.2
32 45 52 60 14 18 23 24 29.8 36.6 43.4
33 46 53 61 14 19 23 25 30.9 37.7 44.6
34 47 54 62 15 19 24 26 31.9 38.8 45.6
35 48 55 63 15 20 24 27 32.9 39.8 46.6
36 49 56 64 16 20 25 28 33.9 40.7 47.5
37 50 57 65 16 21 25 29 34.7 41.6 48.4
38 50 58 65 17 21 21 30 35.6 42.4 49.2
39 51 58 66 17 22 26 31 36.3 43.2 50.0
40 52 59 67 18 22 26 32 37.1 43.9 50.8
33 37.8 44.6 51.4
GA gestational age (Jeanty et al. 1984)
34 38.8 45.3 52.1
35 39.0 45.9 52.7
7.2 The Lens 36 39.6 46.5 53.3
37 40.2 47.0 53.9
The development of the fetal eye: ultrasonographic mea-
Table 7.8 Lens diameters
surements of the vitreous and lens in utero. E. Achiron,
12 GW 3 mm Z. Gottlieb, Y. Yaron, M Gabbay, S Lipitz, S Mashiach.
17 GW 4 mm Prenat Diagn 1995, 15, 155–160
Term 5–6 mm
Never more than 6 mm
Pratique de l’échographie en gynécologie obstétrique (JM
Bouton, M. Denhez, F. Eboué, Vigot, 1990)
GW gestational weeks
6th Percentile
Median
Vitreous circumference 90th Percentile
Millimeters
GA Weeks
Fig. 7.1 Vitreous circumference
7.5 Lens Circumference 205
7.4 Ocular Diameter 7.5 Lens Circumference
Measurement protocol
Table 7.11 Lens circumference
The orbital diameter is measured from the
internal bone edge on one side to the external Centiles
bone edge on the same side. GA (weeks) 5 50 95
12 1.9 5.7 9.6
13 3.5 7.4 11.3
Table 7.10 Ocular diameter 14 4.9 8.8 12.7
15 6.2 10.0 13.9
Centiles
16 7.3 11.1 15
GA (weeks) 5 50 95
17 8.2 12.1 15.9
12 1 3 6
18 9.1 12.9 16.8
13 2 4 7
19 9.8 13.7 17.5
14 3 5 8
20 10.5 14.3 18.2
15 4 6 9
21 11.1 15.0 18.8
16 5 7 9
22 11.7 15.5 19.4
17 5 8 10
23 12.2 16.0 19.9
18 6 9 11
24 12.6 15.5 20.4
19 7 9 12
25 13.1 16.9 20.8
20 8 10 13
26 13.5 17.3 21.2
21 8 11 13
27 13.8 17.7 21.6
22 9 12 14
28 14.2 18.0 21.9
23 10 12 15
29 14.5 18.3 22.2
24 10 13 15
30 14.8 18.6 22.5
25 11 13 16
31 15.1 18.9 22.8
26 12 14 16
32 15.3 19.2 23.0
27 12 14 17
33 15.6 19.4 23.3
28 13 15 17
34 15.8 19.7 23.5
29 13 15 18
35 16.0 19.9 23.7
30 14 16 18
36 16.2 20.1 23.9
31 14 16 19
37 16.4 20.3 24.1
32 14 17 19
33 15 17 19 The development of the fetal eye: ultrasonographic mea-
surements of the vitreous and lens in utero. E. Achiron,
34 15 17 20
Z. Gottlieb, Y. Yaron, M Gabbay, S Lipitz, S Mashiach.
35 15 18 20 Prenat Diagn 1995, 15, 155–160
36 16 18 20
37 16 18 21
38 16 18 21
39 16 19 21
40 16 19 21
Growth of the ocular parameters. Prenatal diagnosis of
congenital anomalies, 1988, table 2–1, 83 R. Romero, G
Pilu, P. Jeanty, A. Ghidini, JC Hobbins
7.6 The Ear
Table 7.12 The fetal ear

GA (weeks) Cases (numbers) Mean Scale
18 7 12.42 2.01
19 11 14.35 1.02
20 44 14.91 1.12
21 135 16.35 1.20
22 200 17.22 1.11
23 97 18.38 1.34
24 28 19.32 1.66
25 16 19.62 1.60
26 6 21.51 2.08
27 9 23.43 1.66
28 16 24.90 2.44
29 18 25.29 2.03
30 12 26.09 2.88
31 27 28.13 1.74
32 49 28.77 1.46
33 19 29.52 1.67
34 8 30.90 1.55
(J. Kerleroux, S. Kerleroux, E. Masse, Médecine fœtale, 1997 no. 29)
Fig. 7.2 Diameter of the lens
7.6 The Ear 207
Fig. 7.3 Ear length

Table 7.13 CV indicates coefficient of variation

Ear length (mm)
GA (weeks) n Mean SD CV%
14 13 8 0.7 9.1
15 14 9 1.8 19.6
16 28 10 0.9 8.8
17 23 11 1.0 8.8
18 26 13 0.7 5.8
19 18 14 1.1 7.9
20 29 15 1.1 7.4
21 18 17 1.0 6.1
22 26 18 1.5 8.3
23 20 19 1.4 7.2
24 13 20 1.1 5.6
25 18 22 1.7 7.9
26 8 23 2.1 8.9
27 17 25 1.7 6.6
28 13 26 1.8 6.8
29 15 26 1.6 6.1
30 9 27 2.3 8.8
31 22 29 2.6 8.9
32 16 29 1.9 6.4
33 16 30 1.8 5.9
34 14 31 1.6 5.3
35 13 31 2.1 6.9
36 11 33 2.6 7.8
37 19 33 2.0 6.3
38 7 33 4.1 12.3
39 7 34 4.3 12.5
40 7 37 2.1 5.7
41 7 36 1.9 5.3
Fetal ear length statistical characteristics according to GA. Prenatal detection of fetal aneuploidy by sonographic ear
length. J. Ultrasound Med, 2003–22:565. L Yeo, ER Guzman, CV Ananth, C Walters, D Day-Salvatore, AM Vintzileos
7.6 The Ear 209
Table 7.14 Normogram of fetal pinna length (mm) according to percentile distribution
Centiles
GA (weeks) n 5 10 25 50 75 90 95
15 10 8.18 8.36 9.00 9.20 10.08 11.47 12.24
16 12 8.83 9.54 9.98 10.60 13.03 13.97 14.00
17 12 12.91 13.02 13.43 14.20 14.73 15.25 15.35
18 11 12.55 12.70 13.80 15.00 16.20 16.70 17.05
19 23 14.00 14.00 15.55 16.00 17.25 17.94 18.00
20 60 15.00 15.40 16.00 17.00 18.00 19.60 20.00
21 88 15.80 16.00 17.00 17.90 19.00 20.20 20.90
22 92 16.20 17.00 18.00 19.00 20.00 21.40 22.50
23 63 17.00 17.60 1840 20.00 21.40 22.60 22.80
24 52 18.50 19.10 19.90 20.90 22.40 23.60 24.00
25 35 18.90 19.10 20.00 21.90 23.00 24.20 24.60
26 39 21.00 21.20 22.40 23.70 25.50 26.80 29.00
27 21 21.60 22.20 23.00 25.00 27.30 28.60 28.60
28 20 24.40 24.90 25.50 26.40 27.10 28.10 28.50
29 18 23.90 24.40 25.00 28.10 29.90 31.60 33.60
30 21 25.00 25.00 27.00 28.00 29.20 31.10 31.30
31 17 26.20 26.30 27.00 28.30 29.90 30.20 31.00
32 29 26.40 27.30 28.00 30.00 31.20 32.20 33.60
33 24 14.70 25.70 28.00 31.40 34.00 34.60 35.00
34 30 27.10 27.70 29.60 32.20 34.30 36.10 37.40
35 33 29.30 30.20 31.10 32.60 34.00 35.80 38.10
36 24 30.00 30.50 31.90 34.00 35.60 36.80 34.40
37 18 29.90 30.40 33.70 35.10 36.40 37.90 38.20
38 13 30.90 31.30 32.20 34.00 37.70 38.20 38.50
39 12 29.60 29.90 32.10 34.90 36.40 37.90 38.90
40 10 29.10 29.20 36.20 37.30 37.90 38.20 39.10
Sonography measurement of fetal pinna length in normal pregnancies. Kathmandu Univ Med J (KUMJ). 2011 Apr-
Jun;9 (34):49–53. KS Joshi, CD Chawla, S Karki, NC Shrestha
7.7 Nasal Bones 7.8 Nose Width
Table 7.15 Length of the nasal bone Table 7.18 The fetal nose width (mm) (Goldstein et al.
1997)
Mean
GA (weeks) (mm) SD −2SD +2SD Centiles
14 4.183 0.431 3.321 5.045 GA (weeks) 10 25 50 75 90
16 5.213 1.062 3.089 7.337 14–15 5.5 7.2 7.6 8.3 10.2
18 6.308 0.654 5.000 7.616 16–17 6.5 7.3 7.9 8.5 10.5
20 7.621 0.953 5.715 9.527 18–19 8.5 8.9 10.0 10.5 11.0
22 8.239 1.102 6.035 10.443 20–21 10.2 11.0 12.0 12.0 13.0
24 9.362 1.300 6.762 11.962 22 13.0 13.0 14.0 15.0 15.0
26 9.744 1.277 7.190 12.298 23 13.0 13.0 14.0 15.0 15.0
28 10.72 1.459 7.803 13.639 24 13.0 14.1 15.0 16.0 16.0
30 11.348 1.513 8.322 14.374 25 14.2 15.0 16.3 17.0 17.0
32 11.580 1.795 7.990 15.170 26 14.1 15.0 16.3 17.4 18.4
34 12.285 2.372 7.541 17.029 27 13.4 15.4 17.2 18.4 19.0
Mean, standard deviation (SD), mean +2SD and mean 28 15.1 16.9 17.6 18.2 20.2
−2SD for length of the nasal bones (mm) throughout ges- 29–30 16.5 17.4 18.1 19.2 20.6
tation (Guis et al. 1995) 31–32 16.6 17.9 19.6 20.7 21.4
33–34 17.4 19.1 20.5 21.4 23.1
Table 7.16 Fetal nasal bone length (mm), 11–20 weeks’ 35–37 17.6 20.0 20.5 22.0 23.3
gestation (Cuick et al. 2004) 38–40 17.4 17.9 18.9 20.5 23.4
GA (weeks) Mean (mm) SD (mm)
11–11.9 1.7 0.5
12–12.9 2.0 0.5
13–13.9 2.3 0.5
14–14.9 3.4 0.7
15–15.9 3.3 0.8
16–16.9 4.4 0.7
17–17.9 5.0 0.7
18–18.9 5.5 0.9
19–19.9 5.7 0.1
20–20.9 6.2 0.1
Table 7.17 Nomogram of fetal nasal bone length at

11–13 gestational weeks in fetuses (Sivri et al. 2006)
GA (weeks) Mean (mm) SD (mm)
11−11 + 6 1.69 0.26
12−12 + 6 2.11 0.37
13−13 + 6 2.34 0.39
14−14 + 6 2.94 0.48
7.9 Nostrils 211
7.9 Nostrils Table 7.20 Measurement of the meant ±2SD of the fron-
tal lobe distance and thalamic frontal lobe distance versus
gestational age (Goldstein et al. 1988)
Table 7.19 The fetal nostril distance (mm) (Goldstein GA FLD Mean TFLD Mean
et al. 1997) (weeks) (cm) ±2SD (cm) ±2SD
Centiles 15 1.4 0.4 3.2 0.4
GA (weeks) 10 25 50 75 90 16 1.4 0.4 3.2 0.4
14–15 3.3 3.6 4.2 4.7 5.4 17 1.6 0.2 3.6 0.6
16–17 3.5 3.9 4.4 4.8 5.9 18 1.6 0,2 3.7 0.6
18–19 4.0 4.4 4.6 5.0 5.8 19 1.7 0.2 3.8 0.4
20–21 4.2 5.0 5.0 5.7 6.0 20 1.7 0.2 4.1 0.4
22 5.0 5.0 6.0 6.4 7.0 21 1.8 0.4 4.1 0.4
23 5.0 5.6 6.0 7.0 7.0 22 1.8 0.4 4.6 0.4
24 5.8 6.0 6.2 7.3 7.9 23 1.8 0.4 4.6 0.4
25 5.9 6.0 6.4 7.0 7.7 24 1.9 0.2 4.7 0.4
26 5.1 6.2 7.7 8.0 9.0 25 2.2 0.4 5.1 0.6
27 6.4 6.8 7.8 8.4 9.4 26 2.3 0.4 5.2 0.6
28 6.4 7.0 7.9 8.6 9.4 27 2.5 0.6 5.6 0.8
29–30 5.4 7.0 7.0 8.2 9.6 28 2.8 0.2 5.7 0.4
31–32 4.6 7.4 7.9 9.2 10.7 29 2.7 0.2 6.1 0.4
33–34 5.4 6.4 8.1 9.0 9.7 30 2.8 0.6 6.2 1.2
35–37 5.8 6.6 8.5 9.6 10.2 31 2.9 0.4 6.2 0.8
38–40 6.0 6.8 8.5 9.5 10.5 32 3.0 0.6 6.4 0.8
33 3.1 0.6 6.5 0.6
34 3.2 0.2 6.7 0.6
35 3.2 0.4 6.9 0.6
36 3.2 0.4 7.0 0.4
37 3.4 0.4 7.2 0.6
38 3.5 0.4 7.3 0.8
39 3.7 0.6 7.5 0.8
40 4.0 0.6 7.7 0.8
GA gestational age, FLD frontal lobe distance, TFLD tha-
lamic frontal lobe distance
7.10 Maxillary Bone Length
Table 7.21 Maxillary bone length across gestationnal age

Xentiles
GA (weeks) n Mean SD 10 50 90
14 17 9.97 1.12 8.32 10.0 11.52
15 59 10.64 1.07 9.4 10.6 11.8
16 13 10.6 1.73 7.6 10.4 12.98
17–19 7 10.07 2.75 7.0 10.9 13.0
20–22 14 11.48 3.42 7.0 11.0 17.35
23–24 15 13.19 3.34 8.6 13.0 16.76
25–26 11 12.85 1.74 10.2 13.0 15.92
27–28 15 12.61 2.11 10.0 12.0 16.2
29–30 16 13.63 1.67 11.67 13.5 16.23
31 15 13.16 1.25 11.0 13.0 15.48
32 18 13.49 1.25 11.9 13.45 15.0
33 20 13.7 1.37 11.11 14.0 15.95
34 25 13.87 1.72 11.96 14.0 16.15
35 28 14.15 1.27 12.54 14.0 16.0
36 28 14.31 1.4 12.63 14.35 16.15
37 12 14.08 1.26 12.93 14.0 16.73
38–39 12 14.84 1.77 11.74 14.8 17.47
Nomogram of maxillary bone length in normal pregnancy. Journal of ultrasound in medicine, September 2005 – 24(9):
1229–1233, I Goldstein, A Reiss, BS Rajamim, A Tamir
7.12 Tongue 213
7.11 Alveaolar Ridge Width 7.12 Tongue
Search of macroglossie (D. Nyberg)

Table 7.22 Normal values of the fetal alveolar ridge Tongue circumference: age (GW) × 2.75
width Ultrasound obstetric gynecology – January
GA (weeks) Mean (mm) +/−SO (mm) 1997 – 39–41. R Achiron, A Ben Arie, U Gabbay,
14–15 10.5 1.3 S Mashiach, Z Rotstein, S Lipitz
16 11.7 1.1
17 16.6 2.5
18 17.5 1.1 Table 7.23 Tongue circumference (mm) by gestational
age and the 95 % confidence interval
19 18.0 1.1
20 18.5 1.1 Lower 95 % Upper 95 %
GA (weeks) Cl Mean Cl
21 18.5 2.1
14 24 28 31
22 19.9 1.7
15 26 33 36
23 20.5 1.9
16 33 36 38
24 21.3 2.7
17 37 37 38
25 22.8 1.9
18 40 43 46
26 23.6 2.6
19 47 48 51
27–28 23.6 2.1
20 47 51 56
29 25.5 2.2
21 51 55 61
30 26.3 2.5
22 52 58 62
31 26.5 2.1
23 58 62 68
32 26.7 2.0
24 60 64 67
Nomogram of the fetal alveolar ridge: a possible screen-
ing tool for the detection of primary cleft palate. 25 68 70 73
Ultrasound obstetric gynecology – November 1999, 14 26 71 73 76
(5), 333–337 Development of the fetal tongue between 14 and 25 weeks
of gestation: in utero ultrasonographic measurements
7.12.1 S
kin Thickness Facing
the Forehead
22 GW: 3.8 mm ± 0.6 mm
Table 7.24 Skin thickness GA (weeks) Skin thickness SD

21 3.44 0.65
22 3.8 0.63
23 3.84 0.61
24 4.22 0.89
25–26 3.91 0.7
27–28 4.83 0.8
29–30 5.16 0.91
31–32 5.78 1.1
33 5.93 1.1
JM Levaillant
N = 638
6.3
6
5.7
5.4
5.1
4.8
mm
4.5
4.2
3.9
3.6
3.3
3
21 22 23 25 24 26 27 28 29 30 31 32 33
Fig. 7.4 Skin thickness GA (weeks)
7.13 Length of Philtrum 215
7.13 Length of Philtrum
Table 7.25 Length of GA (weeks) Mean SD

Philtrum
21 6.06 0.99
22 6.15 0.79
23 6.44 1.03
24 6.47 0.99
25–26 6.7 1.02
27–28 7.34 1
29–30 7.02 1.36
31–32 7.4 1.31
33–34 7.65 1.29
J.M. Levaillant. N = 651
22 GW: 6.15 mm ± 0.7
32 GW: 7.4 mm ± 1.37
Phitrum (mm)
Median
9
8.5
8
7.5
Phitrum (mm)
mm
7 Median
6.5
6
5.5
5
Fig. 7.5 Length of Philtrum 21 22 23 24 25 26 27 28 29 30 31 32 33
GA (weeks)
7.14 The Ears
Table 7.26 Ear length GA (weeks) Ear SD

21 16.35 0.96
22 17.52 0.86
23 18.67 1.47
24 20.03 2.27
JM Levaillant
N = 135
Fig. 7.6 Ear length
7.15 Lower Facial Angle 217
7.15 Lower Facial Angle
Table 7.27 Lower facial angle

GA (weeks) Lower facial angle mean SD
21–24 65.1 7.79
25–27 67.2 8.43
28–34 69.06 7.96
JM Levaillant
N = 422
69.5
69
68.5
68
67.5
Angle
67
66.5
66
65.5
65
64.5
64
Fig. 7.7 Lower facial 21–24 25–27 28–34
angle GA (weeks)
7.16 Upper Facial Angle
Table 7.28 Upper facial angle

GA (weeks) Upper facial angle mean SD
21–24 128.12 10.99
25–28 129.36 13.42
29–34 131.14 12.25
JM Levaillant
N = 454
131.5
131
130.5
130
129.5
Angle
129
128.5
128
127.5
127
126.5
21–24 25–28 29–34
Fig. 7.8 Upper facial
angle GA (weeks)
7.17 Maxillary Width 219
7.17 Maxillary Width
Table 7.29 Maxillary width GA (weeks) Maxillary width mean SD

22 24.8 3.67
23 26.19 4.05
24 27 4.14
JM Levaillant
N = 79
27.5
27
26.5
26
25.5
mm
25
24.5
24
23.5
22 23 24
Fig. 7.9 Maxillary
width GA (weeks)
7.18 Mandibular Width
Table 7.30 Mandibular width GA (weeks) Mandibular width mean SD

22 24.15 2.64
23 25.29 2.53
24 25.4 2.16
JM Levaillant
N = 79
26.5
26
25.5
25
mm
24.5
24
23.5
23
22 23 24
Fig. 7.10 Mandibular
width GA (weeks)
7.19 IOD 221
7.19 IOD 22 GW: 25.2 mm ± 1.3 mm

32 SA: 34.8 mm ± 2.5 mm
A few points of reference IOD/BPD
Median IOD 22 GW: 0.47 ± 0.5–32 SA : 0.42 ± 0.5
Table 7.31 Median IOD GA (weeks) Median IOD mean SD

21 24.24 1.61
22 25.26 1.25
23 25.97 2.32
24 27.04 1.59
25–27 28.86 1.99
28–29 30.91 2.43
31–32 34.15 2.35
33–34 34.49 2.14
JM Levaillant
N = 325
35
34
33
32
31
30
29
mm
28
27
26
25
24
23
21 22 23 24 25 26 27 28 29 31 32 33
GA (weeks)
Fig. 7.11 Median IOD

Table 7.32 Internal IOD Table 7.33 External IOD

GA (weeks) Internal IOD mean SD GA (weeks) External IOD mean SD
21 13.66 1.49 21 34.4 2.56
22 14.09 1.42 22 36.05 2.22
23 14.22 1.57 23 37.55 2.71
24 14.57 1.89 24 39.35 2.1
25–26 15.27 1.81 25–26 40.98 2.72
27–28 16.47 1.56 27–28 43.35 2.48
29–30 16.5 1.63 29–30 48.71 2.75
31–32 17.65 2.19 31–32 50.05 3
33–34 18.14 2.26 33–34 50.84 3.07
JM Levaillant JM Levaillant
N = 660 N = 618
19
18
17
16
mm
15
14
13
12
21 22 23 24 25 26 27 28 29 30 31 32 33
GA (weeks)
Fig. 7.12 Internal IOD
7.19 IOD 223
52
51
50
49
48
47
46
45
44
43
42
mm
41
40
39
38
37
36
35
34
33
32
21 22 24 25 26 27 28 29 30 31 32 33 34
GA (weeks)
Fig. 7.13 External IOD

Normal and Abnormal Fetal Face Atlas 2017

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Normal and Abnormal

ISBN 978-3-319-43768-2 ISBN 978-3-319-43769-9 (eBook)

Library of Congress Control Number: 2017933711

© Springer International Publishing Switzerland 2017

Printed on acid-free paper

This Springer imprint is published by Springer Nature

ultrasound imagery at the Saint-Denis Ultrasound School, with trainers from

1 Introduction Craniofacial Epigenesis in Vertebrates ������������������ 1

3.2 Pierre-Robin Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

7.5 Lens Circumference���������������������������������������������������������������� 205

The facial bones, as they appear in a fetal 1.1  he Key Stages

© Springer International Publishing Switzerland 2017 1

1 Vertebrate embryo in early neurula stage.

Fig. 1.3 The face grows in front of the neural plate

Neural plate Dorsal fusion

Nc: Neural crest

Mouse, D8-D8,5; human, around D22

the optical pits,

Mouse D 8,5; human around D 22-24

Lateral view View from above

Fig. 1.8 Scanning microscope images of anterior neural topology

Fig. 1.10 Human neurula at 27 days (Dr. C. Nilsson)

This human embryo, whose cephalic

Fig. 1.12 Embryonic microsurgery documenting the migration of NC cells

Fig. 1.13 Development of face prominences

Fig. 1.14 Human embryo face at around day 42 Neural

- Facial and cranial osteo-cartilaginous skeleton

- Glial cells (Schwann)

Fig. 1.15 Cellular phenotypes originating from the neural crest

Fig. 1.17 The 6 clefts around the mouth

1.3 Summary Defects in all or part of these molecular strate-

© Springer International Publishing Switzerland 2017 17

2.1  hat Is Included in a Basic

• Continuity of the upper lip • The nose-mouth coronal plane

2.2 Routine Trimester This is a quick analysis, which depends on the

Fig. 2.3 Normal 2D profile

Fig. 2.4 Sagittal view, endovaginal probe

2.2.1.1 What 3D Can Do • A declination of the axial views: frontal arch –

Fig. 2.5 Multiplane 3D images – different view levels

aspects of the face in3D d-orbits

Fig. 2.6 Aspects of the face in 3D

Fig. 2.7 Further images of the face

2.2.2  he Second and Third

Fig. 2.8 2D profile and 2D nose-mouth view

Fig. 2.9 Stepped views (high definition, 2D)

Fig. 2.10 Normal ears

Auricular hypoplasia Pre-auricular

Folds sup edge of helix: Folds upper edge of helix

Fig. 2.11 Abnormal ears

Fig. 2.12 Frontal view of

Fig. 2.13 2D nose-mouth view

2.2.3  potlight on the Third

Capturing a strict profile in A, pinpointing the perfect position in B and C,

Fig. 2.18 Various surface modes

Fig. 2.20 Placement of the probe for a sagittal view

Fig. 2.21 Placement of the probe for an oblique view

Additional Additional sagittal and

Facial Send the patient to referring

2.3 Biometrics of the Face 2.3.1  hickness of the

1 Introduction Craniofacial Epigenesis in Vertebrates �� 1

3.2 Pierre-Robin Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

7.5 Lens Circumference�� 205

The facial bones, as they appear in a fetal 1.1 he Key Stages

1.3 Summary Defects in all or part of these molecular strate-

2.1 hat Is Included in a Basic

2.2 Routine Trimester This is a quick analysis, which depends on the

2.2.1.1 What 3D Can Do • A declination of the axial views: frontal arch –

2.2.2 he Second and Third

2.2.3 potlight on the Third

2.3 Biometrics of the Face 2.3.1 hickness of the

2.4.2 Lower Facial Angle Measurements at 22 and 32 GW

2.4.3 easurements of the Inter-

2.4.4 easurements and Views

2.4.4.1 Comments enable greater analytical precision of the skin

3.1 Clefts There is clearly a predominant association

3.1.3 Ultrasound Diagnosis unilateral cleft, or a tri-partitioning in the case of

3.1.3.3 B asic Principles for Obtaining • frontal mode

3.1.3.4 H D LIVE: Contribution In this evaluation, it is important to look at two

3.1.5 ltrasound Diagnosis of

3.1.6 he Decision-Making Process