Body Wall Defects Research Articles

Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of the Second Case and Phenotypic Assessment.

Casamassima-Morton-Nance syndrome (CMNS) is a rare disorder characterized by spondylocostal dysostosis (SCD), anal atresia, and urogenital anomalies. We describe a fetus with CMNS associated with a limb-body wall defect (LBWD), the second such case in the literature. We compare the phenotypic differences with previously reported cases, including those with segmentation anomalies of the axial skeleton, body wall defects, or absent/abnormal genitalia, revealing the consistent presence of SCD in CMNS. However, as expected, a wide phenotypic spectrum emerges, providing useful observations for fetal/neonatal screening relevant to differential diagnoses. Advanced diagnostic methods using imaging and next-generation skeletal dysplasia multi-gene panels are advisable, as they enable timely, actionable, well-informed decisions for parental counseling, potential elective termination of pregnancy, and prenatal and/or postnatal care. Most reported cases do not mention the recurrence of these usually lethal anomalies.

Limited Role of MSAFP Screening for Prenatal Omphalocele Detection.

Although serum screening for aneuploidies has become less prevalent, maternal-serum alpha-fetoprotein (MSAFP) screening for body-wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P = .97 and P = .87, respectively). In contrast, first-trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P < .01 and P = .01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes.

The sequence of acrania–exencephaly–anencephaly (AEAS)- An infrequent case report

Acrania–exencephaly–anencephaly sequence has an incidence of 3.6–5.4 for 10,000 live births and has been reported in literature. Exencephaly, described here is a defect of the neural tube which occurs due to the absence of closure of the neural fold. The main diagnostic ultrasound features include that are characterized by acrania, decreased size of cranial pole in comparison with the chest, irregular cranial surface, with increased amniotic fluid echogenicity due to the damaged brain tissue. Associated with amniotic band syndrome, Pentalogy of Cantrell, limb anomalies and ventral body wall defects. It is incompatible with life. Conducting programs training the budding neuro-sonographers about the knowledge in detection, diagnosis of NTD according to the Carnegie Classification is crucial to look forward in pathogenesis and application in the clinical scenario.

Acellular Bovine Pericardial Patch for Difficult Abdominal Closure in the Pediatric Population: Our Experience with Review of Literature.

Closure of congenital body wall defects in children can be a challenging task for the pediatric Surgeon. Biological prosthesis has been increasingly used for high-risk wound closure in adult patients with excellent outcomes and use in the pediatric population has also been reported. Here, we aim to study the outcome of abdominal wound repair with a tissue-engineered acellular bovine pericardial patch. Over a period of 21 months, a total of 15 children had undergone abdominal wound repair with bioprostheses, i.e., bovine pericardial patch at our institute. Patient demographics, cause of defect, an indication of patch use, rate of infection, postoperative recovery, recurrence, and outcome were studied. A total of 15 patients underwent abdominal wall closure with acellular bovine pericardial patch. Nine out of 15 patients were neonates, of whom five had gastroschisis, two had a congenital diaphragmatic hernia, and two had ruptured omphalocele major. Of the rest 6 patients, 2 were patients of bladder exstrophy, 2 were older children of congenital diaphragmatic hernia with incisional hernias, and 2 were older children with omphalocele major. Out of the five patients with gastroschisis, two died during the early postoperative period due to sepsis. The wound healed in the rest 13 patients with mild skin dehiscence in two patients. Only one child had a recurrence. Reconstruction with acellular bovine pericardial patch is a viable option in children with high-risk abdominal wounds as it allows tensionless repair with excellent healing and minimal complications. Recurrence, if any, may disappear with time as remodeling of the prosthesis occurs along with the growth of the body wall of the child.

Decoding the dilemma of antenatal ventral body wall defects: A case report and literature review

We are presenting the case of a rare fetal polymalformative syndrome known as the limb body wall complex (LBWC) and its antenatal diagnosis. The level II Anomaly ultrasound of a primigravida female detected exencephaly, thoracoabdominoschisis, club foot, kyphoscoliosis, fetoplacental adherence, and a deficient umbilical cord, classically described in LBWC. It is imperative for radiologists to be familiar with this rare fatal entity of sporadic occurrence and to differentiate it from other non-lethal counterparts for appropriate maternal counseling and timely termination of pregnancy.

Ectopia Cordis with Omphalocele in First Trimester Pregnancy: A Case Report of Incomplete Type of Pentalogy of Cantrell

Ectopia Cordis (EC) is a rare congenital malformation in which the heart is located partially or totally outside the thoracic cavity. It results from the failure of migration of the lateral mesoderm into the midline. The four main ectopic positions are cervical, thoracic, thoracoabdominal and abdominal. EC can manifest as an isolated deformity or as part of a broader group of ventral body wall defects affecting the abdomen, thorax, or both. Pentalogy of Cantrell is a well known association that comprises EC, omphalocele (typically supraumbilical), congenital diaphragmatic hernia, sternal cleft and congenital heart disease. A 27-year-old primigravida came for a routine antenatal ultrasound at 13 weeks of gestation. There was no family history of congenital anomalies, genetic abnormalities, or exposure to teratogenic agents. The ultrasound showed a single foetus corresponding to 13 weeks of gestation with an anterior thoracic defect and an extrathoracic heart, along with partial herniation of the liver near the midline in the epigastric region. These findings were confirmed by foetal Magnetic Resonance Imaging (MRI). An unfavourable prognosis for the foetus was explained to the parents, and medical termination of pregnancy was performed. Therefore, prenatal ultrasonographic diagnosis of EC should be followed by a thorough search for associated defects, as the prognosis may vary.

Autonomous and non-cell autonomous role of cilia in structural birth defects in mice.

Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly. Tamoxifen inducible CAGGCre-ER deletion of a floxed Ift140 allele between E5.5 to 9.5 revealed early requirement for Ift140 in left-right heart looping regulation, mid to late requirement for cardiac outflow septation and alignment, and late requirement for craniofacial development and body wall closure. Surprisingly, CHD were not observed with 4 Cre drivers targeting different lineages essential for heart development, but craniofacial defects and omphalocele were observed with Wnt1-Cre targeting neural crest and Tbx18-Cre targeting epicardial lineage and rostral sclerotome through which trunk neural crest cells migrate. These findings revealed cell autonomous role of cilia in cranial/trunk neural crest-mediated craniofacial and body wall closure defects, while non-cell autonomous multi-lineage interactions underlie CHD pathogenesis, revealing unexpected developmental complexity for CHD associated with ciliopathies.

PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Y-27632 Impairs Angiogenesis on Extra-Embryonic Vasculature in Post-Gastrulation Chick Embryos

Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in various embryonic developmental processes, including angiogenesis, by controlling actin cytoskeleton assembly and cell contractility. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos, leading to ventral body wall defects (VBWDs). Impaired angiogenesis has been hypothesized to contribute to VBWDs. ROCK is essential in transmitting signals downstream of vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis induces gene expressions and alterations of the actin cytoskeleton upon binding to VEGF receptors (VEGFRs). The aim of this study was to investigate effects of Y-27632 on angiogenesis in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Y-27632-treated embryos showed reduced extra-embryonic blood vessel formation with impaired circulation of the yolk sac, confirmed by fractal analysis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated myosin light chain. Interestingly, RT-PCR demonstrated increased gene expression of VEGF and VEGFR-2 1 h post-treatment. Protein levels of VEGF were higher in Y-27632-treated embryos at 8 h following treatment, whereas no difference was seen in membranes. We hypothesize that administration of Y-27632 impairs vessel formation during angiogenesis, which may contribute to failure of VWB closure, causing VBWDs.

Prenatal diagnosis of acrania/exencephaly/anencephaly sequence (AEAS): additional structural and genetic anomalies.

To analyse additional structural and genetic anomalies in fetuses with acrania/exencephaly/anencephaly sequence (AEAS). A retrospective analysis of 139 fetuses with AEAS diagnosed between 2006 and 2020 in a single tertiary referral ultrasound department. The median gestational age at diagnosis decreased from 15weeks in 2006 to 13weeks in 2020 (- 0.21 per each year; p = 0.009). In 103 fetuses, the defects were limited to the neural tube (NTD) (74.1%), in 36 fetuses (25.9%), there were additional structural non-NTD anomalies. The most common were ventral body wall defects present in 17.8% (23/139), followed by anomalies of the limbs (7.2%; 10/139), face (6.5%; 9/139) and heart (6.5%; 9/139). Genetic anomalies were diagnosed in 7 of the 74 conclusive results (9.5%; 7/74; trisomy 18, n = 5; triploidy, n = 1; duplication of Xq, n = 1). In univariate logistic regression models, male sex, limb anomalies and ventral body wall defects significantly increased the risk of genetic anomalies (OR 12.3; p = 0.024; OR 16.5; p = 0.002 and OR 10.4; p = 0.009, respectively). A significant number of fetuses with AEAS have additional structural non-NTD anomalies, which are mostly consistent with limb body wall complex. Genetic abnormalities are diagnosed in almost 10% of affected fetuses and trisomy 18 is the most common aberration. Factors that significantly increased the odds of genetic anomalies in fetuses with AEAS comprise male sex, limb anomalies and ventral body wall defects.

NAD+ deficiency in human congenital malformations and miscarriage: A new model of pleiotropy.

Pleiotropy is defined as the phenomenon of a single gene locus influencing two or more distinct phenotypic traits. However, nicotinamide adenine dinucleotide (NAD+) deficiency through diet alone can cause multiple or single malformations in mice. Additionally, humans with decreased NAD+ production due to changes in pathway genes display similar malformations. Here, I hypothesize NAD+ deficiency as a pleiotropic mechanism for multiple malformation conditions, including limb‐body wall complex (LBWC), pentalogy of Cantrell (POC), omphalocele‐exstrophy‐imperforate anus‐spinal defects (OEIS) complex, vertebral‐anal‐cardiac‐tracheoesophageal fistula‐renal‐limb (VACTERL) association (hereafter VACTERL), oculoauriculovertebral spectrum (OAVS), Mullerian duct aplasia‐renal anomalies‐cervicothoracic somite dysplasia (MURCS), sirenomelia, and urorectal septum malformation (URSM) sequence, along with miscarriages and other forms of congenital malformation. The term Congenital NAD Deficiency Disorder (CNDD) could be considered for patients with these malformations; however, it is important to emphasize there have been no confirmatory experimental studies in humans to prove this hypothesis. In addition, these multiple malformation conditions should not be considered individual entities for the following reasons: First, there is no uniform consensus of clinical diagnostic criteria and all of them fail to capture cases with partial expression of the phenotype. Second, reports of individuals consistently show overlapping features with other reported conditions in this group. Finally, what is currently defined as VACTERL is what I would refer to as a default label when more striking features such as body wall defects, caudal dysgenesis, or cloacal exstrophy are not present.

Combined pentalogy of Cantrell with ectrodactyly and surgical implant‐free repair of a sternal cleft and supraumbilical hernia in an adult cat

AbstractA 20‐month‐old, British shorthair cat was presented for treatment of a ventral thoracic wall defect. Physical examination showed cleft sternum with supraumbilical body wall defect, an immediately palpable heart under the skin between the cleft halves and a unilateral forelimb ectrodactyly. Survey radiographs and sonographic examination revealed ectopia cordis associated with the sternal cleft, a supraumbilical abdominal hernia, ventral diaphragmatic defect and cardiac abnormalities. Radiography of the dysostotic limb confirmed ectrodactyly. Surgery involved reconstruction of the ventral body wall defects using a transversus abdominis muscle flap supported by an omental flap. Clinical, imaging and intraoperative findings supported the diagnosis of complete pentalogy of Cantrell. The cat recovered from surgery uneventfully and periodic follow‐ups to 17 months after surgery confirmed a good outcome.

Limb Body Wall Complex: A Case Report

Limb-body wall complex (LBWC) is a rare, congenital defect defined by lateral body-wall defects, limb reduction abnormalities and/or craniofacial defects. The developmental pathogenesis as well as the etiology of LBW complex is controversial and has no sex or familial predilection. The poor prognosis of LBWC necessitates an early antenatal diagnosis. Serum alpha-fetoprotein measurement and ultrasonographic examination is the key to prenatal diagnosis. Prenatally, the abnormal fetoplacental attachment can be detected ultrasonographically by the end of the first gestational trimester. Postnatal, the examination of placenta, umbilical cord and membranes is crucial in confirming the diagnosis of LBWC. The present case is associated with amniotic adhesive bands, thoraco-abdominoschisis, minor encephalocele, and belongs to the category of LBWC with craniofacial defects.

Types and Distribution of Fetal Congenital Anomaly and their Maternal Characteristics in High Risk Pregnancy Unit of Dhaka Medical College Hospital, Bangladesh

Introduction: Congenital anomaly is one of the important causes of perinatal mortality and morbidity. Proper information regarding its prevalence, distribution as well as risk factors can help policy makers to take appropriate steps for prevention. Materials and Methods: A hospital record based observational study was done in Obstetric department of Dhaka Medical College Hospital, Bangladesh during the year of 2020. The aim of the study is to evaluate the pattern of anomaly found in admitted patients in Maternal Fetal Medicine unit, along with the maternal demographic profile and associated diseases. After taking ethical clearance and permission from department detailed information was collected and analysis was done. Results: In the year 2020 total 6012 delivery was occurred and 4.42% of them were anomalous baby. The maternal characteristics showed that mean maternal age was 26.24(±5.25) years. 20.7% of mother had previous history of abortion, 7.7% has previous perinatal death and 3.3% have previous anomalous baby. 5.49% mother had Diabetic disorders and 4.39% had congenital heart disease. Associated poly hydramnios was found in 17.7% and oligohydramnios was found in 12.1% of cases. The distribution pattern of anomalies according to system involved showed that 41.7% was Central Nervous System anomaly, 8.7% was Renal anomaly, 6.5% was Musculoskeletal anomaly, 4.4% was Gastrointestinal anomaly,6.6% had body wall defect , 10.9 % was Non immune Hydrops, 3.3% was Syndromic baby and 13.1% had multiple congenital anomaly. Conclusion: It is a tertiary hospital based study. So it may not reflect the actual picture of population. So community based study is needed for further advancement.

OEIS Syndrome: Omphalocele, Exstrophy of the Cloaca, Imperforate Anus, and Spinal Defects

OEIS Syndrome: Omphalocele, Exstrophy of the Cloaca, Imperforate Anus, and Spinal Defects

Teratogenesis in the chick embryo following post-gastrulation exposure to Y-27632 -effect of Y-27632 on embryonic development

The pyridine derivative Y-27632 inhibits Rho-associated coiled-coil-containing protein kinase (ROCK) signaling, which is involved in numerous developmental processes during embryogenesis, primarily by controlling actin-cytoskeleton assembly and cell contractility. Somite formation requires rearrangement of the cytoskeleton and assists in major morphological mechanisms, including ventral body wall formation. Administration of Y-27632 impairs cytoskeletal arrangements in post-gastrulation chick embryos leading to ventral body wall defects (VBWD) at later stages of development. The aim of this study was to investigate the effect of Y-27632 on somite development in post-gastrulation chick embryos during early embryogenesis. After 60 h incubation, embryos in shell-less culture were treated with Y-27632 or vehicle for controls. Following administration, abnormality rates were assessed. In treatment groups, embryos showed a kinked longitudinal body axis. Western blot confirmed impaired ROCK downstream signaling by decreased expression of phosphorylated cofilin-2. Histology, Lysotracker studies and RT-PCR demonstrated increased cell death in somites, the neural tube and the ectoderm. RT-PCR and Western blot of factors known to be involved during somitogenesis revealed reduced expression in the treatment group compared to controls. We hypothesize that administration of Y-27632 disrupts somite development causing axial kinking and embryo malformation, which may lead to VBWD.

Body stalk anomalies in pig-Definition and classification.

The presence of body wall closing defects (abdominoschisis and thoracoabdominoschisis) in combination with other congenital malformations was studied in the pig (Sus scrofa domesticus). After clinical examination and literature review, body wall defects with multiple congenital anomalies in eight pigs were described, and classified using anatomical and embryological criteria. Several BSA presentations were identified and classified as follows: (a) BSA Type I: fetus with spinal and UC defects, thoracoabdominoschisis, anal atresia and/or other internal organs structural defects, and structural limb defects; (b) BSA Type II: fetus with spinal and UC defects, thoracoabdominoschisis, anal atresia and/or other internal organs structural defects, and nonstructural limb defects; (c) BSA Type III: fetus with spinal and UC defects, abdominoschisis, anal atresia and/or other internal organs structural defects, and structural limb defects; and (d) BSA Type IV: fetus with spinal and UC defects, abdominoschisis, anal atresia and/or other internal organs structural defects, and nonstructural limb defects. Two types of LBWC were differentiated: LBWC Type I: characterized by thoracoabdominoschisis and structural limb defects, and LBWC Type II: characterized by abdominoschisis and structural limb defects, corresponding to BSA type I and type III. This is the first report on BSA and LBWC in the pig.

Body Wall Defects: Gastroschisis and Omphalocoele in Pigs (Sus scrofa domesticus)

Body wall defects (BWDs) are not well studied and categorized in veterinary medicine. BWDs can be an isolated occurrence, but often occur with other major developmental abnormalities. Thirty-two body wall malformations of domestic pigs (Sus scrofa domesticus) are presented and classified, distinguishing between body wall dysplasia (umbilical hernia, abdominal wall distension and gastroschisis), omphalocoele and thoracoabdominoschisis (Cantrell syndrome, shistosomus reflexus, body stalk anomalies).

Fetal Autopsy Showing Two Ventral Body Wall Defects: An Unusual Presentation

Thoracoschisis and gastroschisis are types of ventral body wall defects. Usually thoracoabdominoschisis presents as a continuous defect. Here the authors present the case of autopsy of 18 weeks old fetus with two well-separated ventral body wall defects. Thoracoschisis was a right lateral thoracic wall defect while gastroschisis, a midline infraumblical abdominal wall defect. Through the right lateral thoracic wall parts of two organs appeared to be protruding. On dissection, 8th and 9th ribs with the liver and the lower lobe of the right lung were herniating outside the body. The right lung was haemorrhagic. Various embryological theories on ventral body wall defects have been discussed in view of the present case.

Cantrell Syndrome (Thoracoabdominal Ectopia Cordis; Anomalous Umbilical Cord; Diaphragmatic, Pericardial and Intracardiac Defects) in the Pig (Sus scrofa domesticus)

Pentalogy of Cantrell (PC) is a complex body wall defect, involving the abdominal wall, sternum, diaphragm, pericardium and heart. We report on six stillborn piglets with anomalous umbilical cord (UC), cranio-umbilical abdominal defect, cleft sternum, incomplete diaphragm and pericardium, ectopia cordis and intracardiac anomalies. Anomalous UC was defined as a single umbilical artery (SUA) and/or short cord, or as an UC with atypical coiling pattern. The embryonic period, in which all the anomalies found in these piglets develops, coincides with that of UC formation in the pig. We propose that anomalous UC should be considered a sixth defect in Cantrell syndrome (CS), considering that the insult leading to the classical malformations of PC and UC abnormalities is the same or that the sequence of malformations itself may alter the early fetoplacental blood flow and therefore the normal development of the UC angioarchitecture. CS has not been reported previously in animals.