Prenatal sonography of extracorporeal ductus venosus in association with large fetal gastroschisis.

Liver herniation commonly associated with omphalocele occurs in only approximately 2.3% to 16% of fetuses with gastroschisis. Liver herniation in such cases is associated with considerably decreased survival rates (43% vs 97% with or without liver herniation, respectively). Rarely, abnormally positioned fetal hepatic vasculature has been reported mainly in association with congenital diaphragmatic hernia. In these rare cases, intrathoracic depiction of hepatic venous vasculature has assisted in confirming intrathoracic displacement of the fetal liver. We present a case of a large gastroschisis with complete herniation of the fetal liver in which prenatal sonography depicted an extracorporeal ductus venosus.

Vermiform Appendix During the Repackaging Process from Umbilical Herniation to Fixation onto the Right Posterior Abdomen: A Study of Human Fetal Horizontal Sections.

The anatomical position of the vermiform appendix varies among adults, and these variations are responsible for differences in the symptoms of appendicitis. However, to date no study has examined how and when these variations occur during fetal development. The present study examined horizontal sections of 27 midterm fetuses (crown rump length [CRL] 38-97 mm, gestational age approximately 8-15 weeks). There were 10 fetuses (CRL 56 mm or more) in which the cecum and appendix were in a posterosuperior site near the right kidney (postmigration phase), and 12 fetuses (CRL 39-72 mm) in which the ileocecal junction and appendix remained on the visceral surface of the liver in the anterior or anterolateral abdominal cavity (migration phase, after physiological umbilical herniation). Analysis of the 12 fetuses in the migration phase indicated that the appendix extended inferiorly in eight fetuses and superiorly in four fetuses. Likewise, a "preileal" appendix (a morphology in which the distal part of the appendix was in front of the terminal ileum) was present in eight of these fetuses. Extension of the appendix superiorly or inferiorly during the migration phase seems unrelated to the topographical relationship of the appendix with the terminal ileum at the postmigration phase in fetuses and in adults. Conversely, it seems likely that a retroileal appendix leads to a coiled appendix behind the ileocecal junction. "Guidance" by the liver surface seemed to be important for posterior migration, which ended with the ascent of the liver. Clin. Anat., 33:667-677, 2020. © 2019 Wiley Periodicals, Inc.

Kagami-Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report.

BACKGROUND: Kagami-Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region. Its clinical manifestations include polyhydramnios in the fetal stage, respiratory insufficiency because of a small thorax, abdominal wall abnormalities, and peculiar facial features after birth. CASE PRESENTATION: A 38-year-old Japanese primigravida woman was referred to our hospital in the 19th week of pregnancy for suspected omphalocele. She had a history of hypothyroidism but was prescribed orally administered levothyroxine (50 µg/day) prior to conception and was euthyroid. Her ultrasound scan prior to visiting our hospital revealed fetal omphalocele, heavy for date, and polyhydramnios. The mother was advised to be admitted for observation from 28 weeks of gestation for threatened premature delivery. She required amniodrainage at 29 and 32 weeks of gestation. At 35 weeks of gestation, the fetal membrane prematurely ruptured and she gave birth after an emergency Cesarean section. The infant was a male child with a birth weight of 3188 g, and was suspected to have Kagami-Ogata syndrome after birth based on thoracic hypoplasia, swallowing function abnormalities, and peculiar facial features. A definitive diagnosis was established by performing genetic testing of the infant after obtaining informed written consent from both the parents; the results of the genetic testing revealed hypermethylated intergenic-differentially methylated region and maternally expressed gene 3-differentially methylated region in the corresponding chromosome 14 region. Both the parents were genetically tested after adequate genetic counseling, which revealed a de novo microdeletion in a differentially methylated region. CONCLUSION: Kagami-Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.

Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes.

OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases. STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed. RESULTS: Out of 63 fetal cases, 33 were live-born, > 50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach to omphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p = 0.006). CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

Cardiac anomalies associated with omphalocele.

Omphaloceles are ventral abdominal wall defects that are associated with significant other anomalies in up to 80% of cases in some descriptions. Of these abnormalities, Cardiac defects are some of the more common ones, and have the most substantial impact on outcomes and survival. In cases with a severe congenital heart defect (CHD), the omphalocele management changes significantly. This article addresses the common defects seen, and their management issues.

Insights into embryology and development of omphalocele.

Congenital abdominal wall defects are one of the most common human birth defects with an incidence of about 1 in 2000 live births. While often discussed together abdominal wall defects consist mainly of two distinct entities namely gastroschisis and omphalocele. There is no clear consensus explaining the precise embryological mechanisms leading to the development of an omphalocele. Many clinicians and embryologists have attempted to explain congenital malformation as a result of failure of progression of normal embryonic development. This review summarizes the mechanisms involved in normal and abnormal development of the ventral abdominal wall.

Relationship Between Physiological Umbilical Herniation and Liver Morphogenesis During the Human Embryonic Period: A Morphological and Morphometric Study.

It is widely hypothesized that physiological umbilical herniation (PUH) in humans occurs, because the liver occupies a large space in the abdominal cavity, which pushes the intestine into the extraembryonic coelom during the embryonic period. We have recently shown the presence of the intestinal loop in the extraembryonic coelom in embryos with liver malformation. Here, we analyzed the relationship between the liver and the PUH at Carnegie stage 21 of four embryos with liver malformation, including two with hypogenesis (HY1, HY2) and two with agenesis (AG1, AG2), using phase-contrast X-ray computed tomography and compared them with two control embryos. The intestinal loop morphology in the malformed embryos differed from that in the control embryos, except in HY1. The length of the digestive tract in the extraembryonic coelom of the embryos with liver malformation was similar to or longer than that of the controls. The rate of intestinal loop lengthening in the extraembryonic coelom compared with that of the total digestive tract in all embryos with liver malformation was similar to or higher than that of the controls. The estimated total abdominal cavity volume in the embryos with liver malformation was considerably smaller than that of the controls, while the intestinal volume was similar. The cardia and proximal portion of the pancreas connecting to the duodenum were located at almost identical positions in all the embryos, whereas other parts of the upper digestive tract deviated in the embryos with abnormal livers. Thus, our results provided evidence that PUH occurred independently of liver volume. Anat Rec, 302:1968-1976, 2019. © 2019 American Association for Anatomy.

Gestational Outcomes of Pregnancies with Prenatally Detected Gastroschisis and Omphalocele.

Objective: To evaluate and compare the outcomes of pregnancies with prenatally detected gastroschisis and omphalocele. Materials and Methods: We retrospectively evaluated prenatally detected gastroschisis and omphalocele cases. Cases were compared in terms of maternal demographic and clinical characteristics as well as pregnancy and neonatal outcomes. Results: This study consisted of 17 gastroschisis and 30 omphalocele cases. Only one case with gastroschisis was terminated due to additional severe limb deformities. Seventeen out of 30 cases of omphalocele were terminated for various reasons (56.7%). All patients with gastroschisis had surgical repair, while 8 out of 13 omphalocele cases had surgery. One patient with an omphalocele died after surgery due to sepsis. Six cases of gastroschisis also died in the neonatal period due to various reasons (6/16, 37.5%). Conclusion: Additional genetic disorders are more frequent in those with omphalocele cases, and they are more frequently terminated during gestation that the gastroschisis fetuses.

Return of the intestinal loop to the abdominal coelom after physiological umbilical herniation in the early fetal period.

The intestine elongates during the early fetal period, herniates into the extraembryonic coelom, and subsequently returns to the abdominal coelom. The manner of herniation is well-known; however, the process by which the intestinal loop returns to the abdomen is not clear. Thus, the present study was designed to document and measure intestinal movements in the early fetal period in three dimensions to elucidate the intestinal loop return process. Magnetic resonance images from human fetuses whose intestinal loops herniated (herniated phase; n = 5) while returning to the abdominal coelom [transition phase; n = 3, crown-rump length (CRL)] 37, 41, and 43 mm] and those whose intestinal loops returned to the abdominal coelom normally (return phase; n = 12) were selected from the Kyoto Collection. Intestinal return began from proximal to distal in samples with CRL of 37 mm. Only the ileum ends were observed in the extraembryonic coelom in samples with CRLs of 41 and 43 mm, whereas the ceca were already located in the abdominal coeloms. The entire intestinal tract had returned to the abdominal coelom in samples with CRL > 43 mm. The intestinal length increased almost linearly with fetal growth irrespective of the phase (R2  = 0.90). The ratio of the intestinal length in the extraembryonic coelom to the entire intestinal length was maximal in samples with CRLs of 32 mm (77%). This ratio rapidly decreased in three of the samples that were in the transition phase. The abdominal volumes increased exponentially (to the third power) during development. The intestinal volumes accounted for 33-41% of the abdominal volumes among samples in the herniated phase. The proportion of the intestine in the abdominal cavity increased, whereas that in the liver decreased, both without any break or plateau. The amount of space available for the intestine by the end of the transition phase was approximately 200 mm3 . The amount of space available for the intestine in the abdominal coelom appeared to be sufficient at the beginning of the return phase in samples with CRLs of approximately 43 mm compared with the maximum intestinal volume available for the extraembryonic coelom in the herniated phase, which was 25.8 mm3 in samples with CRLs of 32 mm. A rapid increase in the space available for the intestine in the abdominal coelom that exceeded the intestinal volume in the extraembryonic coelom generated an inward force, leading to a 'sucked back' mechanism acting as the driving force. The height of the hernia tip increased to 8.9 mm at a maximum fetal CRL of 37 mm. The height of the umbilical ring increased in a stepwise manner between the transition and return phases and its height in the return phase was comparable to or higher than that of the hernia tip during the herniation phase. We surmised that the space was generated in the aforementioned manner to accommodate the herniated portion of the intestine, much like the intestine wrapping into the abdominal coelom as the height of the umbilical ring increased.

Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures. PURPOSE: To address the temporal requirement of Pdgfra in embryonic development. METHODS: We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies. RESULTS: Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives. CONCLUSION: Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies.

High prevalence of same-sex twins in patients with cloacal exstrophy: Support for embryological association with monozygotic twinning.

PURPOSE: Previous studies have hypothesized that cloacal exstrophy may be caused by errors early in embryological development related to monozygotic twinning. This study reports the prevalence of twins in a large cohort of patients with cloacal exstrophy. METHODS: Patients with cloacal exstrophy treated 1974-2015 were reviewed for reports of multiple gestation or conjoined twinning. The genetic sex of the patient and their twin, and any mention of anomaly in the twin were recorded. Neither placental exam nor genetic testing results were available to definitively determine zygosity. RESULTS: Of 71 patients, 10 had a live born twin (14%), all of whom were of the same genetic sex as the affected patient. One additional patient's twin suffered intrauterine fetal demise, and another patient had a conjoined heteropagus twin. None of the twins were affected by exstrophy-epispadias complex. The rate of twin birth in this cohort was 4.4-7.7 higher than that reported by the Centers for Disease Control in the general population time period (P<0.001), with a striking preponderance of same-sex pairs. CONCLUSIONS: The highly significant prevalence of same-sex twin pairs within this cohort supports the hypothesis that the embryogenesis of cloacal exstrophy may be related to errors in monozygotic twinning. LEVEL OF EVIDENCE: 2b.

Impact of holoprosencephaly, exomphalos, megacystis and increased nuchal translucency on first-trimester screening for chromosomal abnormalities.

OBJECTIVES: To examine the prevalence of alobar holoprosencephaly, exomphalos, megacystis and nuchal translucency thickness (NT) ≥ 3.5 mm, the incidence and types of chromosomal abnormalities associated with these conditions and their overall impact on the rate of invasive testing and performance of screening at 11-14 weeks. METHODS: This was a prospective screening study for trisomies 21, 18 and 13 by the first-trimester combined test at three maternity units in England. RESULTS: In the study population of 108 982 singleton pregnancies, 870 (0.8%) had abnormal karyotype, including 654 (75.2%) with trisomies 21, 18 or 13 and 216 (24.8%) with other chromosomal abnormalities. The prevalence of alobar holoprosencephaly, exomphalos, megacystis and NT ≥ 3.5 mm was 1 in 2945, 1 in 419, 1 in 1345 and 1 in 119, respectively. Chromosomal abnormalities were observed in 78.4% of cases of holoprosencephaly, 40.8% of exomphalos, 18.5% of megacystis and 48.5% of those with NT ≥ 3.5 mm. The most common chromosomal abnormality associated with holoprosencephaly was trisomy 13, with exomphalos and megacystis was trisomy 18 and with increased NT was trisomy 21. Fetal karyotyping of cases with major fetal defects or increased NT would potentially detect 57% of all chromosomal abnormalities at an invasive testing rate of 1.1%. CONCLUSION: Major fetal defects and increased NT at 11-13 weeks' gestation are associated with a high risk of chromosomal abnormalities and merit invasive fetal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

When Closure Fails: What the Radiologist Needs to Know About the Embryology, Anatomy, and Prenatal Imaging of Ventral Body Wall Defects.

Ventral body wall defects (VBWDs) are one of the main categories of human congenital malformations, representing a wide and heterogeneous group of defects sharing a common feature, that is, herniation of one or more viscera through a defect in the anterior body wall. Gastroschisis and omphalocele are the 2 most common congenital VBWDs. Other uncommon anomalies include ectopia cordis and pentalogy of Cantrell, limb-body wall complex, and bladder and cloacal exstrophy. Although VBWDs are associated with multiple abnormalities with distinct embryological origins and that may affect virtually any system organs, at least in relation to anterior body wall defects, they are thought (except for omphalocele) to share a common embryologic mechanism, that is, a failure involving the lateral body wall folds responsible for closing the thoracic, abdominal, and pelvic portions of the ventral body wall during the fourth week of development. Additionally, many of the principles of diagnosis and management are similar for these conditions. Fetal ultrasound (US) in prenatal care allows the diagnosis of most of such defects with subsequent opportunities for parental counseling and optimal perinatal management. Fetal magnetic resonance imaging may be an adjunct to US, providing global and detailed anatomical information, assessing the extent of defects, and also helping to confirm the diagnosis in equivocal cases. Prenatal imaging features of VBWDs may be complex and challenging, often requiring from the radiologist a high level of suspicion and familiarity with the imaging patterns. Because an appropriate management is dependent on an accurate diagnosis and assessment of defects, radiologists should be able to recognize and distinguish between the different VBWDs and their associated anomalies. In this article, we review the relevant embryology of VBWDs to facilitate understanding of the pathologic anatomy and diagnostic imaging approach. Features will be illustrated with prenatal US and magnetic resonance imaging and correlated with postnatal and clinical imaging.

Development of the ventral body wall in the human embryo.

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body.

Registry analysis supports different mechanisms for gastroschisis and omphalocele within shared developmental fields.

Nine thousand two hundred eighty abnormalities associated with 2,943 abdominal wall defects (AWD) encoded from 1999 to 2008 by the Texas Birth Defects Registry (TBDR) were classified and analyzed for mechanism, beginning with 1,831 gastroschisis cases, 774 (41%) with 2,368 associated anomalies (AA) and 814 of omphalocele, 727 (89%) with 4,092 AA. Typical AA profiles for Trisomy 18 (23% of omphalocele cases) and Beckwith-Wiedemann syndrome (15%) validated registry AA descriptors, chromosome disorders surprisingly accounting for 24% of known conditions with gastroschisis followed by expected amniotic band (ADAM) complex (23%) and amyoplasia/arthrogryposis (16%). Separation of known diagnoses, fetal-stillbirth cases, and transitional or secondary AA left 330 cases of gastroschisis with 594 AA (452 major, 142 minor) and 295 cases of omphalocele with 956 AA (683 major, 273 minor). Anomalies suggestive of vascular origin (intestinal atresias, amyoplasia, bands) were more frequent with gastroschisis and those of defective lateral folding (exstrophies, limb-body wall defects) with omphalocele. Most AA favoring omphalocele had parallel frequencies with gastroschisis, whether by system/region-for example, cardiac AA (10% of cases), contractures (4.7%), limb (3.7%), CNS (3.2%) for gastroschisis versus cardiac (35%), contractures (14%), digestive-excretory-trunk-axial (all ∼11%), CNS (9.9%) for omphalocele-or for particular minor/major AA-for example, micrognathia (0.72% versus 3.3%), spina bifida (0.59% versus 3.9%), anal atresia (0.73% versus 6.4%), two-vessel cord (0.22% versus 5.6%). Similar frequencies of many AA reflective of early patterning support common AWD origin within early developmental fields and reinforce the use of large birth defect numbers from suitably qualified registries to define anomaly mechanism as well as prevalence.

Possible Genetic Origin of Limb-Body Wall Complex.

Limb body wall complex (LBWC) is characterized by multiple severe congenital malformations including an abdominal and/or thoracic wall defect covered by amnion, a short or absent umbilical cord with the placenta almost attached to the anterior fetal wall, intestinal malrotation, scoliosis, and lower extremity anomalies. There is no consensus about the etiology of LBWC and many cases with abnormal facial cleft do not meet the requirements for the true complex. We describe a series of four patients with LBWC and other malformations in an attempt to explain their etiology. There are several reports of fetuses with LBWC and absent gallbladder and one of our patients also had polysplenia. Absent gallbladder and polysplenia are associated with laterality genes including HOX, bFGF, transforming growth factor beta/activins/BMP4, WNT 1-8, and SHH. We postulate that this severe malformation may be due to abnormal genes involved in laterality and caudal development.

A chicken embryo model for the study of umbilical and supraumbilical body wall malformations.

UNLABELLED: BACKGROUND/PURPOSE; The embryology of ventral body wall malformations is only partially understood, although their incidence is relatively common. As only few experimental data exist on the development of those defects, the aim of our study was to compare the teratogenic effect of trypan blue (TB) and suramin (SA) in their capability to induce umbilical and supraumbilical abdominal wall malformations in a chicken egg model. MATERIALS AND METHODS: A total of 255 fertilized chicken eggs were incubated at 38 °C and 75% relative humidity. Embryos were treated in ovo on incubation day 2.5 (Hamburger/Hamilton (HH) stage 13). The eggshell was windowed, and solutions of TB or SA were injected into the coelomic cavity at the region of the umbilicus. The window was closed and the embryos reincubated until examination on day 8 (HH 34). RESULTS: A total of 60 embryos survived in each group. The largest number of embryos presented with defects in the umbilical and supraumbilical region (25% in the SA group and 40% in the TB group). A combination of both defects (thoracoabdominoschisis) was seen in 20% of the TB and 8.3% of the SA groups, respectively. Associated anomalies found in both groups were head and eye defects, abnormal pelvic configurations, leg deformities, and mild forms of cloacal exstrophies. CONCLUSIONS: TB and SA have both a high potential to induce umbilical and supraumbilical ventral body wall malformations in chicken embryos. This novel animal model might help to establish a more profound understanding of the developmental steps in ventral body wall formation and the embryology for its malformations.

Fetal syringomyelia.

We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyelia in Chiari malformations, infarct like histology, or old hemorrhage in 8 cases of syringomyelia. Vernicomyelia did not occur in the absence of syrinx formation. The syringes extended from the sites of dysraphism, in ascending or descending patterns. The syringes were usually in a major proportion anatomically distinct from a dilated or denuded central canal and tended to be dorsal and paramedian or median. We suggest that fetal syringomyelia in Chiari II malformation and other dysraphic states is often established prior to midgestation, has contributions from the primary malformation as well as from secondary in utero injury and is anatomically and pathophysiologically distinct from post natal syringomyelia secondary to hindbrain crowding.

Liver agenesis with omphalocele: a report of two human embryos using serial histological sections.

We identified 2 human embryos, with crown-rump lengths (CRLs) of 22 mm and 23 mm and a gestational age of approximately 7 weeks (O'Rahilly's stage 21-22), with liver agenesis and omphalocele. Serial histological sections were prepared of the entire body of one specimen, whereas sections of the neck, including the upper part of the heart, were missed for the other specimen as a result of tissue damage during the abortion. In addition, isolated omphalocele was assessed in another embryo (CRL  =  25 mm) for comparison with atypical omphalocele in the embryos with liver agenesis. The 2 embryos with liver agenesis were characterized by (1) the absence of the anterior part of the diaphragm; (2) abnormality in the venous pole of the heart; (3) a normal stomach in the left upper abdominal cavity; and (4) normal pancreas development with normal midgut rotation. The most likely cause of liver agenesis, when combined with isolated omphalocele, was a defect in the anterior extension or migration of the septum transversum rather than a mechanical separation of the hepatic diverticulum from the septum transversum.