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Lara Spalldi Barii*, Milan Stanojevi, Asim Kurjak, Selma Porovi and Ghalia Gaber
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652Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
Table 1:Prenatal diagnosis of 18selected congenital anomaly subgroups for registries with complete EUROCAT data from 2010 to 2014 [1].
Includes the following registries: Antwerp (Belgium), French West Indies (France), Isle de la Reunion (France), Saxony-Anhalt (Germany),
Cork and Kerry (Ireland), SE Ireland, Emilia Romagna (Italy), Tuscany (Italy), Malta, N Netherlands (NL), S Portugal, Basque Country (Spain),
Valencia Region (Spain), Vaud (Switzerland), Wales (UK), Ukraine.
However, implementing new ideas and knowledge from When to suspect a syndrome
scientific research along with taking advantage of pro-
gress in available diagnostic equipment make prenatal prenatally and how to detect it
detection much more accurate and precise. With the recent
dynamic and quick development of computer technology, Common terminology used to describe fetal syndromes
like 3D high definition live (3D HDlive) silhouette and can sometimes be confusing. A wide variety of terms and
flow US technology, there has been an enormous break- synonyms are used. Sometimes, there is a lack of good
through in US equipment, with remarkable image quality. definitions of how many major and minor criteria should
Thanks to highly specialized software systems, it is possi- be present to diagnose each syndrome. The difference in
ble to view fetal anatomy in the smallest detail [2] and the prenatal detection rates for each region or country can be
dynamics of fetal structural and functional development partly explained by differences in screening policies and
in real time. Using four-dimensional (4D) technology, one follow-up practices, as well as the possible variations in
can get an idea of the functionality of some organs and practitioners skills and available equipment [8].
systems, for example, the brain or the eye, introducing Clinical dysmorphology is a branch of clinical genetics
new fields of fetal assessment like fetal neurology or fetal dedicated to the study of abnormal human development,
sono-ophthalmology [3]. Some new functional tests have with emphasis on syndromes expressed mostly as altera-
even been introduced in everyday clinical practice, like tions in body morphology [14, 15]. There are many patho-
the Kurjak antenatal neurodevelopmental test (KANET), physiological mechanisms for fetal maldevelopment,
to assess the function of the fetal brain [47], adding which can be described as malformation, deformation,
some additional valuable input into the diagnosis of fetal disruption or dysplasia [16]. Malformation is commonly
syndromes [8]. Many authors reported a shift of prenatal defined as a single localized poor formation of tissue initi-
detection of fetal syndromes from the 2nd to the 1st trimes- ating a sequence of defects (e.g. anencephaly). The recur-
ter of pregnancy [3, 8, 913]. rence risk for malformations generally range from 1% to
The aim of this paper is to present and discuss the 5%. Deformation is a result of extrinsic mechanical forces
possibilities of different US techniques to improve the on otherwise normal tissue, deforming it (e.g. abnormal
detection rates of some fetal syndromes prenatally. faces, pulmonary hypoplasia and limb contractures that
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound653
result from prolonged oligohydramnios or primary renal (2D) US should always be followed to avoid mistakes in
agenesis in Potter syndrome with Potter facies). Disrup- prenatal assessment [8]. When evaluating structures like
tion results from an extrinsic insult that destroys normal the fetal spine or the face, 3D/4D US renders much more
tissue, altering the formation of affected structure (e.g. accurate images [18]. Magnetic resonance imaging (MRI)
amniotic band syndrome). If the primary defect is absence has comparable image quality with US, which is the most
of normal organization of cells into tissue, then we speak commonly used modality for pregnancy evaluation. US
of dysplasia (e.g. achondroplasia) [8, 16]. provides cost-effective real-time imaging, offers high reso-
Any of the mechanisms of fetal maldevelopment can lution and is considered safe for the mother and the fetus
result in altered morphology of fetal organs and systems, [19]. US is superior to any other imaging technology in
which can result in the formation of a fetal syndrome if pregnancy because of the possibility to be used from the
many organs are involved. The word syndrome originates early 1st trimester [18], with the possibility to assess fetal
from ancient Greek meaning running together [17], rep- movements in almost real-time [18]. Undoubtedly, one of
resenting a specific pattern of associated signs, symptoms, the best non-invasive diagnostic tools for the detection
dysmorphic features and/or behaviors occurring together and visualization of fetal anomalies and syndromes is US,
in the same individual [8, 14, 15]. particularly 3D/4D US [9]. With recent advances in 3D/4D
Some fetal syndromes can be detected prenatally while technology, antenatal diagnosis of fetal anomalies and
others cannot; some are expressed prenatally while others syndromes greatly shifted from the 2nd to the 1st trimester
are not. In many cases definitive diagnosis can be made of pregnancy [9, 11, 18].
posnatally, many years later [8]. The differential diagnosis Goncalves et al. [20] reviewed 525 articles on 3D/4D
of fetal syndromes is wide, and there are several available sonography and found that 3D US provides additional
databases online that can be of assistance in the recogni- diagnostic information for the diagnosis of facial anom-
tion of patterns of anomalies as a syndrome, sequence or alies, especially facial clefts, neural tube defects and
association [8]. The most widely used online databases are skeletal malformations.
Online Mendelian Inheritance in Man (OMIM), Orphanet, Merz and Welter [21] examined a large group of 3472
London Dysmorphology Database, Possumweb and the fetuses evaluated with detailed 2D and 3D US targeted
Phenotip online database. For the sonographer, the most for fetal anomalies. The total number of defects was
user-friendly database, especially designed to include all 1012. Comparing the 2D and 3D techniques, 3D US proved
antenatal sonographic findings (instead of postnatal find- advantageous in 60.8% of the defects, which was related
ings), is the Phenotip online database, while the London to the favorable demonstration of targeted areas in differ-
Dysmorphology Database and Possumweb are non-free ent views (e.g. multiplanar, surface view) [21, 22].
databases, constructed to aid in differential diagnosis, with Only in the last several years have high-frequency
the inclusion of postnatal findings. There is quick access to transducers and HDlive technology made major improve-
the information, with the possibility to search by ultrasono- ments in the quality of US imaging. The 3D HDlive ren-
graphic marker, a combination of a few markers or just by the dering method takes advantage of shadowing effects
name of the syndrome. The triggers to investigate even more to improve the visualization of details on the image [23].
carefully for the syndrome could be known family history, Unlike conventional 3D surface rendering that uses a
earlier pregnancy with malformed fetus/infant, history of fixed virtual light source and reflects the light off the skin
consanguinity, exposure to some teratogenic drug or other surface, HDlive rendering calculates the propagation of
agents, traveling to high-risk areas and possible exposure light through the skin and the tissue [23]. Shadows are
to some infections (Zika virus, TORCH infections) or trauma created where light has moved through denser tissues.
[8]. There is also the possibility to include parental markers The virtual light source can be changed and directed
if present. Synonyms of the syndromes are included in the easily from any angle and can be manipulated to enhance
search automatically, which makes it easier and faster. segmentation of tissue structures, define precise outlines
and highlight important clinical details [23]. This tool is
handy when observing surfaces, particularly of the facial
Clinical application of 3D/4D area. Any suspected area or malformation can be investi-
ultrasound in the prenatal detection gated and visualized much better than with conventional
2D US. By changing the angle of virtual light, one can
of fetal syndromes adjust it perfectly to emphasize and get depth perception
in visualizing a region of interest that may be an anomaly.
An optimized and systematic approach (guidelines) to the A translucent effect is gained if the light source is placed
evaluation of the fetus by conventional two-dimensional behind the object [23]. Enhanced smoothing is obtained
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654Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
by volume-speckle reduction imaging (V-SRI) on quality of the pericallosal artery (PA) (Figure 1) and the anterior
multi-planar 3D/4D rendered images by applying volume cerebral artery (ACA) became much easier than before [12,
(voxel) vs. traditional single slice (pixel) imaging. 32]. If there is a suspicion or clear prenatal diagnosis of
HDlive rendering can be successfully applied during agenesis of CC (ACC), it is important to search for other fetal
the entire pregnancy [18]. In the 1st trimester, normal and abnormalities or syndromes [trisomy 18, cerebro-costo-
abnormal embryonal and fetal developments can be fol- mandibular syndrome, Walker-Warburg syndrome, Pai
lowed and evaluated in the smallest detail. Early and mid- syndrome, Fryns syndrome and also fetal varicella zoster
trimester anomaly scans can be aided with 3D/4D HDlive syndrome, fetal cytomegalovirus (CMV) syndrome and the
technology in detecting fetal anomalies and syndromes, most recently recognized congenital fetal Zika virus syn-
as suggested by many studies [10, 18, 2426]. Only 2years drome, etc.] [33]. Despite the fact that we are able to recog-
ago, new applications in 3D US called HDlive silhouette nize some structural anomalies prenatally, the prediction
and HDlive flow were launched. HDlive silhouette found of the exact extent of the damage and prognosis may still
its clinical significance in imaging simultaneously the be a challenge [7, 32].
inner morphology through the outer surface in a transpar-
ent fashion. This helps in mapping the exact location and
volume of inner structures, which can be hyperechoic, Congenital heart defects
such as bone, or hypoechoic, such as a cyst [12]. HDlive
flow adds more spatial resolution to a conventional angio- Congenital heart defects (CHD) are the most common con-
gram. With the simultaneous combination of both tech- genital anomalies occurring more frequently than chro-
niques (HDlive silhouette and flow), one can visualize the mosomal malformations and spinal defects together. The
exact location of vascular structures inside the organs and incidence is estimated to about 413 per 1000 live births,
map the direction of the vascular flow (3D HDlive bidi- representing a significant cause of fetal mortality and
rectional power Doppler). These two novel applications morbidity [34].
enabled the visualization of intracorporeal vascularity, Prenatal diagnosis of CHD by US is difficult, demand-
premature forebrain, midbrain and hindbrain, as well as ing thorough training and expertise. The detection rate of
flow in the brain vessels. CHD is variable and it ranges from 35% to 86% in most
The use of a skin-like color tone in HDlive gave an even studies [34]. In the past, many attempts were made to
more realistic impression of a live fetus, with impressive improve the prenatal detection rate of CHD. Four-dimen-
pictorial illustration [3, 712, 18, 2430]. Many of the earlier sional US (real-time 3D US) used for fetal cardiac assess-
mentioned innovations in 3D/4D US applications are par- ment may improve visualization of cardiac anatomy and
ticularly beneficial in the prenatal detection and visualiza- allow better evaluation of valvular function [20].
tion of anomalies of the fetal face and its discreet details. Early evaluation of the fetal heart as well as recog-
The fascinating combination of science, research and new nition of several major cardiac abnormalities frequently
technologies is all together implemented in a new upcom- coexisting in many fetal syndromes (Down syndrome,
ing research program called Give a face to a syndrome [8, Edwards syndrome, DiGeorge syndrome, tarsal tunnel syn-
31]. Facial Dysmorphology Novel Analysis (FDNA) is a new drome, etc.) can be obtained by 3D/4D US and improved
technology that facilitates detection of facial dysmorphic by special applications [8, 12, 18, 26]. Two-dimensional US
features and recognizable patterns of human malforma- is still the technique of choice for the prenatal diagnosis of
tions (postnatal/adult life) to present comprehensive and CHD; however, the last decade has shown some promising
up-to-date neurogenetic references available online [8, 31]. results due to advanced 3D/4D US technology [34], such
as advanced spatio-temporal image correlation (STIC),
volume contrast imaging (VCI) and Omni view. STIC is
Brain anomalies a technological development of 3D/4D US developed to
assist the detection of CHD. An automated device is incor-
An important milestone in the prenatal recognition of porated into the ultrasound probe that has the capacity to
normal brain development is the visualisation of corpus perform a slow sweep to acquire a single 3D volume [34].
callosum (CC) by improved ultrasound imaging; without Acquisition of volume data of the fetal heart and connec-
this prenatal assessment was rather difficult. With 3D tions is done (the intraventricular septum, atrioventricu-
surface rendering in the median plane, CC can be visual- lar valves, great vessels outflow tracts, aorta and ductal
ized with all its segments: genu, body and splenium. Addi- arch) by allowing multiplanar and surface reconstruction
tionally, vascularization of CC with a 3D sonoangiogram of the heart anatomy [34]. The sonographer, even when
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound655
less experienced in fetal echocardiography, can acquire among them; CHD [conotruncal, ventricular septal defect
volume data, which can be digitally stored and analyzed (VSD), tetralogy of Fallot] in more than 40% of cases,
later or sent to a (fetal echocardiography) expert for facial dysmorphysm (hyperthelorism, bulbous nasal tip),
further analysis. For better evaluation, the acquired data cleft palate, hypoplasia/aplasia of the thymus, malfor-
can be also assessed in the cine loop feature [34], played mation of cortical brain development (polymycrogyria),
in slow motion and stopped any time to evaluate cardiac missing ribs, open spina bifida, polydactyly and clubfoot
or vascular structures of interest. This application is also are the most common (Figure2) [33]. All the above-men-
very helpful in counselling the parents and showing them tioned malformations can be detected prenatally by US.
where the problem is when CHD is found in the fetus. Beside the heart anomalies, thymic hypoplasia/aplasia
is known to be a typical feature in this condition, and
Chaoui etal. [35] suggested that fetal thymic US can be
Detecting the syndrome from an additional parameter in the assessment of fetuses
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656Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
A B
While evaluating fetal faces, one must consider ethnic Syndromes featuring primarily craniofacial
variations and normal differences. For example, an epi- anomalies
canthal fold may be normal for people of Asiatic descent
and for some non-Asian infants, but it can be considered Paramedian cleft lip (CL) or cleft palate (CP) or a combina-
as a dysmorphic feature of syndromes such as Down syn- tion of the two (Figure 3) are the most common fetal facial
drome, Turner syndrome, Noonan syndrome, Williams anomalies and one of the most common fetal anomalies.
syndrome, fetal alcohol syndrome, etc. Different shape They occur between the 8th and 9th gestational week and
of the nose in different ethnic groups is another example can be unilateral or bilateral. If this is an isolated finding
(Mediterranean, African, Asian, Hispanic and Cauca- (in less than 50% of cases), the defect can be surgically
sian). A broad-beaked nose is a feature of Wolf-Hirschhorn repaired with a good postoperative result. Unfortunately, a
syndrome (Greek warrior helmet syndrome) [33] and a majority of the fetuses with CL or CP have high incidence of
short-beaked nose of some craniosynostosis-associated chromosomal abnormalities and other associated anoma-
syndromes like Apert syndrome, Pfeiffer syndrome, lies as part of syndromes [37]. Carriers of Van der Woude
Crouson syndrome, etc. [37]. A bulbous nose tip is feature (VdW) syndrome have facial clefts in 50% of cases. VdW
of DiGeorge syndrome, as mentioned earlier. However, if syndrome has an autosomal dominant mode of inherit-
there is a syndrome, there will be other associated anoma- ance, which accounts for approximately 2% of all cases of
lies too. So even a small deviation from the normal can be CL and CP [37]. Incomplete unilateral small CL can easily
a trigger and clue to look further and raise awareness of be missed by conventional 2D US, while 3D HDlive surface
possible syndromes. rendering is a better method to detect it. Bilateral CL can
A B C D
Figure 3:Paramedian cleft lip (CL) or cleft palate (CP) or a combination of the two (CL/P).
(A) Prenatal detection of unilateral paramedian right CL/P by 3D HDlive surface rendering in fetus with detected Edwards syndrome (trisomy
18). (B) Postnatal presentation of unilateral paramedian right CL/P. (C) Postnatal presentation of unilateral paramedian left only CL. (D) Post-
natal presentation of bilateral paramedian CL/P.
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound657
Figure 5:Prenatal detection of micrognathia with low-set ears by 3D HDlive surface rendering.
(A) In a fetus with detected Pierre- Robin sequence (PRS). (B) In a fetus with Meckel-Gruber syndrome (courtesy of S. Panchal).
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658Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
first year of life and the adjusted profile of the child can could occur in the timeline between the 4th and 8th weeks
be expected between the 3rd and 6th year of life [3840]. of gestation [44]. However, Wang etal. [45] analyzed data
Isolated PRS (without any other associated malformation) from a large congenital birth defects registry in Spain
occurs in about 50% of cases; however, in the other half and found a connection between diabetic mothers and
of the cases, PRS is part of a malformation syndrome. The increased risk of their infants being born with OAV syn-
clinical expression of the syndrome depends on the exist- drome. There has been speculation that poorly controlled
ence and severity of associated anomalies [37]. The nature maternal diabetes interferes with cephalic neural crest
of these anomalies is diverse most commonly, the first cell migration, causing this syndrome [45]. The first sono-
branchial arch anomalies, various chromosomal disorders graphic clue for the detection of this syndrome (also with
(DiGeorge syndrome), collagenopathies or syndromes conventional 2D US imaging) can be finding asymmetry of
associated with toxic agents such as alcohol (fetal alcohol the face due to hemifacial macrosomia or something small
syndrome), etc. In the review of 115 cases of patient with and very typical as periauricular skin tags (Figure 7).
PRS, as expected, 54% had PRS as an isolated finding. By using 3D surface rendering, more can be evaluated.
The others included syndromes such as Stickler syndrome Unilateral craniofacial anomaly underdevelopment of one
(18%), velocardiofacial syndrome (7%), Treacher Collins side of the body can include brain (cerebellar hemisphere
syndrome (TCS) (5%), facial and hemifacial microsomia hypoplasia) [45], eye (micro/anophtalmia), low-set ears
(3%) and other defined (3.5%) and undefined disorders with malformation, face (asymmetry of the soft tissue),
(9%) [8, 40]. Facial dysmorphism commonly arises from kidney (hydronephrosis), etc. With the application of 3D
a combination of migration and inadequate formation of HDlive imaging technology, even small details of the face
facial mesenchyme (especially when associated with dis- and other body parts can be visualized in a very realis-
orders of the first and second branchial arches) [41]. tic way, which can be very helpful while counseling the
Goldenhar syndrome (GS) or oculo-auriculo-vertebral parents. The combination of micrognathia with low-set
(OAV) syndrome is the combination of such abnormalities ears is a common finding in many syndromes. Detection
[37]. It is characterized by a wide spectrum of symptoms, of bilateral symmetric hypoplasia of the face, preauricular
facial and associated features that may differ in range tags in combination with micrognathia may be part of TCS,
and severity from one case to another (Figure 6). A classic Nager syndrome or Miller syndrome. TCS is a congenital
feature of GS is asymmetric (mostly unilateral) hypoplasia disorder of craniofacial development caused by mutations
of the face. Fetuses with GS have major anomalies, such in the TCOF1 gene on chromosome 5q32 [33]. TCS is repre-
as unilateral mandibular hypoplasia with involvement sented by bilateral symmetrical otomandibular dysplasia
of the temporomandibular joint and multiple skin tags (Figure8). TCS is often associated with downward slant-
around the ear, ear hypoplasia/aplasia and/or eye malfor- ing of the palpebral fissures. There could be associated
mations (microphthalmia/anophthalmia) and vertebral head and neck defects, and abnormalities of the extremi-
anomalies. Typically, these malformations are unilateral ties can be also found. The incidence of TCS is estimated
(70%) and give an asymmetric appearance of the face. at 1:50,000 live births per year. The inheritance is autoso-
Usually, the right side is more severely affected than the mal dominant with variation in expressivity. Cranioskel-
left [4244]. There have been some theories about the etal hypoplasia develops due to an insufficient number
origin of this condition. Some authors hypothesized that of neural crest cells as a consequence of neuroepithelial
the problem could be unilateral disruption of the blood progenitor cell death [46]. The onset of defects occurs very
supply (ischemia) to the 1st and 2nd brachial arches, which early in embryogenesis between the 4th and 8th weeks of
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound659
Figure 7:Prenatal 3D surface rendering image of preauricular tag, postnatal images of external ear deformity, small ipsilateral half of the
face and microphtalmia.
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660Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
with the Apert syndrome is defect on the extremities, are limb defects (constriction rings, amputation of the
called mitten-like hands/feet: syndactyly (soft tissue limb or digits, etc.) and anterior abdominal wall defects
and osseous) of the 2nd, 3rd and 4th finger in combination (gastroschisis, omphalocele) (Figure 10) [16, 37]. Other
with a broad thumb. Pooh and Kurjak [13] published a skull abnormalities detected by US are microcephaly and
case of a prenatally detected fetus with Apert syndrome macrocephaly. Microcephaly indicates a group of disor-
by using 3D sonography. Correlation was made between ders characterized by a small head and typically asso-
prenatal 3D US images of anomalies and identical post- ciated with abnormal neurological findings and mental
natal appearance [13, 18]. Three-dimensional US images disabilities [37]. Microcephaly usually also implies micro-
can be used to present the parents with the extent of encephaly because the head size is commonly determined
the abnormalities of the face, skull and extremities [48]. by the brain size. Fetuses with prenatally suspected
Parents should be counseled about prognosis, possibility microcephaly have head circumference (HC) >3standard
of different degrees of intellectual impairment and risk deviations (SDs) below the mean for gestational age [50].
of recurrence. When resulting from a de novo mutation, Different associated US features depend greatly on the
recurrence risk is improbable, but if one of the parents is a etiologic factor causing microcephaly. The exact etiology
carrier, the recurrence risk is 50%. There may be an asso- of most microcephaly cases is still unknown. However, it
ciation between advanced paternal age and higher risk of is linked to numerous syndromes associated with chro-
occurrence of Apert syndrome as a single-gene disorder mosomal abnormalities like Cornelia de Lange syndrome,
[49]. To confirm the diagnosis prenatally, the option of AC DiGeorge syndrome, Wolf-Hirshhorn syndrome, cri-du-
should be offered to the parents. chat syndrome, trisomy 13 and 9, etc., exposure to some
Frontal bossing may be a typical finding in achondro- toxic agents (alcohol, drugs, chlomiphene, methotrexate,
plasia (autosomal dominant condition with rhizomelic phenylalanine), maternal under-nutrition and certain
limb shortening) (Figure 9) and Russell-Silver syndrome maternal infections during pregnancy, such as rubella,
(short stature, asymmetric intrauterine growth restriction toxoplasmosis, varicella and cytomegalovirus (CMV).
of the skeleton with normal size of the head). Asymmetry There are reports of a new causation between maternal
of the fetal skull can also be found in the fetus with amni- infection and Zika virus during pregnancy and adverse
otic band syndrome (sequence). Due to rupture in the pregnancy outcomes such as microcephaly, other brain
amnion, which initiates the process very early in the 1st and eye defects and pregnancy loss [51]. Zika congenital
trimester of pregnancy, the amniotic band causes a wide syndrome is generally characterized by cerebral atrophy
variety and severity of destructive fetal malformations, that may interfere in formation and neuronal migration
depending on fetal parts that come in contact and get during early cerebral embryogenesis [52]. Other features
trapped in it. When affecting the skull, asymmetric anen- of this syndrome are the following: severe microcephaly,
cephaly, encephalocele, facial clefting and micrognathia lissencephaly, cataract of the eye, microophtalmia, club-
can be detected. Other abnormalities that are also found foot, contractures and arthrogryposis [5153]. Viruses
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound661
A B C D
E F G H
Figure 10:Prenatal detection of omphalocele at 13+3 gestational weeks. Different ultrasound modes and rendering applications are used to
visualize the omphalocele.
(A) Conventional 2D mode. (BD and EG) 3D HDlive surface rendering with different angle of illumination. (H) Postnatal presentation of the
baby born at 40 gestational weeks, realistic and same appearance of omphalocele in the prenatal compared to the postnatal period.
such as CMV or Zika have been shown to invade the brain In addition, infection may cause scars and calcifications
cells, particularly neural progenitors, infect and destroy in the brain tissue. Abnormalities such as periventricular
the primary stem cells (the radial glial cells) of the brain; and intraparenchymal calcifications, ventriculomegaly
therefore, there is a lack of future daughter neurons secondary to cerebral atrophy, cerebellar hypoplasia and
[5456]. The severity of the condition may depend on the cortical abnormalities are seen and detected much earlier
timing of infection during pregnancy. Microcephaly is than microcephaly itself. Besides the standard US screen-
mostly the result of decreased size of the cerebral cortex. ing, fetal neurosonography as well as KANET should be
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662Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound
performed and repeated in the follow-up period until the first few days of life due to pulmonary hypoplasia
the delivery. The infection should be confirmed by the and renal failure. Detection of occipital encephalocele
real-time reverse transcription polymerase chain reac- in the 1st trimester is easier due to a better overview and
tion (rRT-PCR) [53]. The most recent follow-up studies normal collection of amniotic fluid. Later in pregnancy,
from Brazil have shown that even though some babies are there is progressive oligohydramnios and encephalocele
born with a normal head size, postnatal development of
microcephaly can still occur as well as significant neuro-
logical sequelae also leading to arthrogryposis, a condi-
tion resulting in deformities of joints [52]. In the prenatal
assessment of pregnancies at risk, evaluation with 4D
US and KANET could be included. Prenatal results can
be compared with postnatal results of neonatal neuro-
logical evaluation in the follow-up period during the first
23years of life [68].
During a routine anomaly scan, abnormalities of
fetal kidneys can be detected. A wide variety of structural
and functional abnormalities can be seen (Figure 11).
Dysplastic kidneys with multiple cysts [multcystic dys-
plastic kidneys (MCDK)] that fluctuate in size can be
found in some very severe syndromes. As MCDK are dys-
functional, it could be a lethal condition called Meckel-
Gruber syndrome (Figure 12) with autosomal recessive
inheritance [57], if found bilaterally. Three pathogno- Figure 14:3D HDlive surface rendering of normal appearance of
monic anomalies can be found: occipital encephalocele, fetal face at 28 gestational weeks.
MCDK (Figure13) and polydactyly. Neonates die within KANET assessment by 4D. Notice the open eye.
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Barii etal., Diagnosis of fetal syndromes by 3D/4D ultrasound663
may be missed. Special attention should be paid to eval- approved by the authors institutional review board or
uate both fetal kidneys because normal sonographic equivalent committee.
finding of kidneys rules out the lethal Meckel-Gruber
syndrome.
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Antenatal detection of fetal syndromes by ultrasound: from a
there is also a lot of room for improvement. As the new
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Authors Statement
[12] Pooh RK. Novel application of hdlive Silhouette and hdlive
Conflict of interest: Authors state no conflict of interest. flow: clinical significance of the see-through fashion in pre-
Material and Methods: Informed consent: Informed natal diagnosis. Donald School J Ultrasound Obstet Gynecol.
consent has been obtained from all individuals included 2016;10:908.
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of fetal anomalies. Donald School J Ultrasound Obstet Gynecol.
Ethical approval: The research related to human subject
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