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The congenital condition gastroschisis is associated with delayed villous development and placental malperfusion, suggesting placental involvement. This study uses RNA sequencing to compare the placental transcriptome in pregnancies with and without gastroschisis. 180 coding genes were differentially expressed, mapping to multiple gene ontology pathways. Altered placental gene expression may represent fetal signalling to the placenta, and these changes could contribute to the pathogenesis of gastroschisis and associated morbidities, including fetal growth restriction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Gastroschisis and omphalocele are the most common congenital abdominal wall defects. The main purpose of this study was to investigate the incidence, other associated anomalies and the course of these diseases in Iceland., Material and Methods: The study was retrospective. The population was all newborns who were admitted to the NICU of Children's Hospital Iceland due to gastroschisis or omphalocele in 1991-2020. Furthermore, all fetuses diagnosed prenatally or post mortem where the pregnancy ended in spontaneous or induced abortion, were included., Results: During the study period, 54 infants were born with gastroschisis and five with omphalocele. The incidence of gastroschisis was 4.11 and omphalocele 0,38/10,000 births. There was no significant change in the incidence of the diseases during the study period. In addition, five fetuses were diagnosed with gastroschisis and 31 with omphalocele where the pregnancy was terminated. In addition to gastroschisis in the live born infants and fetuses the most common associated anomalies were in the gastrointestinal or urinary tract but in infants and fetuses with omphalocele anomalies of the cardiac, central nervous or skeletal systems were the most common. Sixteen fetuses diagnosed with omphalocele had trisomy 18. Mothers aged 16-20 were more likely to give birth to an infant with gastroschisis than older mothers (p< 0.001). Primary closure was successful in 86% of the infants. Those reached full feedings significantly earlier and were discharged earlier. Overall survival rate was 95%. Three children were still receiving parenteral nutrition at discharge due to short bowel syndrome., Conclusions: The incidence of gastroschisis in Iceland is in accordance with studies in other countries but but the incidence of omphalocele is lower, which can be partly explained by spontaneous or induced abortions. Other anomalies associated with omphalocele are more severe than those associated with gastroschisis. Primary closure was associated with more benign course. Children with gastroschisis may need prolonged parenteral nutrition due to shortening of their intestines.

Objective: Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs., Methods: Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR)., Results: BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05)., Conclusions: The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

The pathogenesis of omphalocele and gastroschisis is not obvious. Their etiology is disputed. The prevalence and the types of anomalies co-occurring with omphalocele and gastroschisis are variable in the different series published. The aim of this study was to estimate the frequency and the types of co-occurring anomalies in cases with gastroschisis and omphalocele. This study was performed in a well-described population of 387,067 consecutive births between 1979 and 2007. Hundred-one cases with omphalocele were registered (2.61 per 10,000), 75 (74.3%) had co-occurring anomalies comprising chromosomal anomalies (28 cases, 27.7%, including 18 trisomy 18), non-chromosomal syndromes (16 cases, 15.8%, including 3 cases with Beckwith-Wiedemann syndrome, 2 cases with the OEIS sequence, and one case with the Pentalogy of Cantrell complex), and 31 cases, 30.7% with MCA (multiple congenital anomalies). The most common MCA were musculoskeletal (23.5%), urogenital (20.4%), cardiovascular (15.1%), and central nervous (9.1%). Seventy-one cases of gastroschisis were ascertained (1.83 per 10,000). However, the prevalence increased during the study period. The frequency was highest in the mothers 15-19 years old. Sixteen out of the 71 cases with gastroschisis, (22.5%) had co-occurring anomalies including 11 cases of MCA and 5 cases with syndromes. To conclude, the frequency and the types of anomalies co-occurring with omphalocele and gastroschisis are peculiar. Therefore, cases with gastroschisis and omphalocele need to be screened for co-occurring anomalies., (© 2021 Wiley Periodicals LLC.)

Objective: The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors., Method: Genome-wide DNA methylation analysis of 96 blood samples was performed using the Illumina Human Methylation 850K BeadChip. The blood samples were collected as follows: 32 from the umbilical cord of fetuses with gastroschisis, 32 from their respective mothers, 16 from the umbilical cord of fetuses without malformation, and 16 from their respective mothers., Results: The differential DNA methylation analysis showed a significant difference between the groups. The enrichment analysis resulted in 12 sites related to T-cell activation (p = 0.0128). The sites with different methylation status contained 10 genes, three of which were related to the beta-2-microglobulin gene. The methylation profile observed in the fetuses with gastroschisis was not inherited from the mothers. In addition, there was no association between maternal urinary tract infection, smoking, and alcohol use and different methylated sites., Conclusion: We established the methylation profile of gastroschisis fetuses, which differs from that of normal fetuses. The profile was not inherited and did not correlate with maternal risk factors., (© 2020 John Wiley & Sons Ltd.)

Gastroschisis and omphalocele are the two most common abdominal wall birth defects, and epidemiologic characteristics and frequency of occurrence as part of a syndromic condition suggest distinct etiologies between the two defects. We assessed complex patterns of defect co-occurrence with these defects separately using the Texas Birth Defects Registry. We used co-occurring defect analysis (CODA) to compute adjusted observed-to-expected (O/E) ratios for all observed birth defect patterns. There were 2,998 non-syndromic (i.e., no documented syndrome diagnosis identified) cases with gastroschisis and 789 (26%) of these had additional co-occurring defects. There were 720 non-syndromic cases with omphalocele, and 404 (56%) had additional co-occurring defects. Among the top 30 adjusted O/E ratios for gastroschisis, most of the co-occurring defects were related to the gastrointestinal system, though cardiovascular and kidney anomalies were also present. Several of the top 30 combinations co-occurring with omphalocele appeared suggestive of OEIS (omphalocele, exstrophy of cloaca, imperforate anus, spinal defects) complex. After the exclusion of additional cases with features suggestive of OEIS in a post-hoc sensitivity analysis, the top combinations involving defects associated with OEIS (e.g., spina bifida) were no longer present. The remaining top combinations involving omphalocele included cardiovascular, gastrointestinal, and urogenital defects. In summary, we identified complex patterns of defects that co-occurred more frequently than expected with gastroschisis and omphalocele using a novel software platform. Better understanding differences in the patterns between gastroschisis and omphalocele could lead to additional etiologic insights., (© 2020 Wiley Periodicals LLC.)

Background: Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis., Methods: We employed WES in two affected half-sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS-PhoRank and Ensembl-Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS-PhoRank) and functional properties (Ensembl-Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes., Results: No single gene-disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63-linked ubiquitination, protein-containing complex assembly, and regulation of transcription DNA-templated., Conclusion: Considering the likely gene-disrupting prediction results and similar biological pattern of mechanisms, we propose a joint "multifactorial model" in gastroschisis pathogenesis., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objectives: Gastroschisis remains an etiologic dilemma. We posit that an underlying genetic susceptibility either separately or coupled with a periconceptional environmental exposure stimulates an inflammatory response resulting in gastroschisis. To investigate the genetic link, we applied shared genomic segment (SGS) analysis, a novel approach to discover chromosomal segments that inherit in high-risk multigenerational pedigrees., Methods: We studied pedigrees containing distantly related children with gastroschisis originating from a common ancestor. We used the Illumina OmniExpress genotyping array with >700,000 SNPs. Samples from 40 affected children in 13 pedigrees (≥3 affected children) were genotyped to generate the high-density SNP data necessary to perform SGS analysis. Assessment of significance in SGS was determined empirically using simulations based on precise pedigree structure and modeling linkage disequilibrium (LD) for SNPs in the general population to properly account for genetic architecture. The LD model was estimated from the 1000 Genome Project using the same set of SNPs. Genome-wide significance thresholds were determined for each pedigree., Results: We identified six pedigrees that contained genome-wide statistically significant SGS regions inherited from a common founder. These regions were different in each pedigree, all contained immune pathway genes., Discussion: The genome-wide significant regions support a genetic susceptibility for gastroschisis. The regions are compelling candidates for regionally focused genome sequencing, enabling the discovery of coding or noncoding (e.g., regulatory) risk variants, the latter of which are unlikely to be found using conventional exomic/gene-focused approaches. This technique provides a comprehensive and focused genomic interrogation that will help to advance our understanding of gastroschisis., (© 2019 Wiley Periodicals, Inc.)

We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9 , and FGFR4 . SVS-PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B , SLC9A3 , ITGA2 , AOX1 , and ALPP , including a recessive model in UGT1A7 , UGT1A6 , PER2 , PTPRD , and UGT1A3 . A heterozygous compound model was observed in CDYL, KDM5A , RASGRP1 , MYBPC2 , PDE4DIP , F5 , OBSCN , and UGT1A . These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.

Background: Gastroschisis has been assumed to have a low rate of syndromic and primary malformations. We aimed to systematically review and explore the frequency and type of malformations/chromosomal syndromes and to identify significant biological/genetic roles in gastroschisis., Methods: Population-based, gastroschisis-associated anomalies/chromosomal defects published 1950-2018 (PubMed/MEDLINE) were independently searched by two reviewers. Associated anomalies/chromosomal defects and selected clinical characteristics were subdivided and pooled by race, system/region, isolated, and associated cases (descriptive analysis and chi-square test were performed). Critical regions/genes from representative chromosomal syndromes including an enrichment analysis using Gene Ontology Consortium/Panther Classification System databases were explored. Fisher's exact test with False Discovery Rate multiple test correction was performed., Results: Sixty-eight articles and 18525 cases as a base were identified (prevalence of 17.9 and 3% for associated anomalies/chromosomal defects, respectively). There were 3596 associated anomalies, prevailing those cardiovascular (23.3%) and digestive (20.3%). Co-occurring anomalies were associated with male, female, American Indian, Caucasian, prenatally diagnosed, chromosomal defects, and mortality (P < 0.00001). Gene clusters on 21q22.11 and 21q22.3 (KRTAP), 18q21.33 (SERPINB), 18q22.1 (CDH7, CDH19), 13q12.3 (FLT1), 13q22.1 (KLF5), 13q22.3 (EDNRB), and 13q34 (COL4A1, COL4A2, F7, F10) were significantly related to biological processes: blood pressure regulation and/or vessel integrity, angiogenesis, coagulation, cell-cell and/or cell-matrix adhesion, dermis integrity, and wound healing (P < 0.05)., Conclusions: Our findings suggest that gastroschisis may result from the interaction of several chromosomal regions in an additive manner as a pool of candidate genes were identified from critical regions supporting a role for vascular disruption, thrombosis, and mesodermal deficiency in the pathogenesis of gastroschisis.

Background: Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies., Methods: Genetic association studies of gastroschisis published 1980-2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP-gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity., Results: Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher's exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis., Conclusions: Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene-gene or gene-environmental interactions are warranted for better understanding the etiology of gastroschisis.

Purpose: To evaluate the occurrence of gastroschisis attributable to familial factors in a Mexican population-based setting., Methods: A descriptive study was performed among gastroschisis cases born from 2010 through 2016 at Tijuana General Hospital (Baja California, Mexico) to generate multigenerational pedigrees., Results: There were 87 gastroschisis cases from 57,217 live births. Six probands (6.9%) had another affected family member. Two half-siblings, a set of monozygotic twins, a mother-and-daughter occurrence, a distant paternal cousin and a distant maternal uncle were identified. Sibling recurrence was 5.5%. From 174 males and 153 females studied (n=327, involving 180 nuclear families), sex-dependent influence analysis evidenced an increased susceptibility to gastroschisis in males (3.2%) compared to females (1.8%) with an overall of 2.5% adjusted for proband., Conclusions: Our results provide a greater liability attributable to familial factors on gastroschisis. In spite of the predominant sporadic occurrence, underlying genetic susceptibility and environmental influences point to a complex interplay between genes and environmental factors in gastroschisis., Level of Evidence: Level IV., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: There is uncertainty over whether familial recurrences in gastroschisis might be higher. Moreover, scant information is available regarding its sociodemographic features. We aim to explore the recurrence risk, sex-dependent influence, and geographical distribution of familial gastroschisis., Methods: A systematic review of the literature and data extraction from population-based studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features from 11 studies were pooled including 862 probands as a base. A descriptive analysis and Chi-square test were performed., Results: Twenty-four probands had a positive family history of gastroschisis including 49 affected family members, for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence was 4.3%. Sex-dependent influence analysis (n = 879, from three studies) evidenced an increased susceptibility to gastroschisis in males (2.5%) compared to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's exact test (P = 0.023)., Conclusion: Our findings support a greater liability attributable to familial factors on gastroschisis along with significant information for family and prenatal counseling. We suggest that future studies should include for a more accurate account for both familial and environmental confounding factors to uncover relatives and environmental exposures that more limited family histories may have missed.

In a population-based case-control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (OR h ) or homozygous variants (OR v ) genotypes. These included NOS3 (rs1036145) OR h  = 0.4 (95% CI: 0.2-0.7); NOS3 (rs10277237) OR v  = 2.7 (95% CI: 1.3-6.0); ADD1 (rs12503220) OR h  = 2.9 (95% CI: 1.6-5.4), GNB3 (rs5443) OR h  = 0.2 (95% CI: 0.1-0.5), OR v  = 0.4 (95% CI: 0.2-0.9); ICAM1 (rs281428) OR v  = 6.9 (95% CI: 2.1-22.9), ICAM1 (rs3093030) OR v  = 2.6 (95% CI: 1.2-5.6); ICAM4 (rs281438) OR v  = 4.9 (95% CI: 1.4-16.6), ICAM5 (rs281417) OR h  = 2.1 (95% CI: 1.1-4.1), OR v  = 4.8 (95% CI: 1.7-13.6); ICAM5 (rs281440) OR h  = 23.7 (95% CI: 5.5-102.5), OR v  = 20.6 (95% CI: 3.4-124.3); ICAM5 (rs2075741) OR v  = 2.2 (95% CI: 1.1-4.4); NAT1 OR v  = 0.3 (95% CI: 0.1-0.9). There were additional associations between several gene variants and gastroschisis among women aged 20-24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc., (© 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.)

Background: Gastroschisis is a developmental disorder involving the extrusion of fetal intestines through a defect in the abdominal wall. The mechanism is presumed to be a dual vascular/thrombotic pathogenesis, where normal right umbilical vein involution forms a possible site for thrombosis adjacent to the umbilical ring., Purpose: The aim of this study was to demonstrate that the 3 common prothrombotic polymorphisms, MTHFR c.677C>T, F2 c.20210G>A, and F5 Leiden, were elevated in frequency in Indonesian gastroschisis patients., Material and Methods: Three genetic markers were investigated in 46 patients with gastroschisis and 89 ethnicity-matched controls for association studies using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or TaqMan Genotyping Assays on genomic DNA., Results: MTHFR c.677C>T showed a significant association with gastroschisis (OR = 2.1, 95% CI = 1.13-3.86; p = .018) but no affected infants had risk alleles for either F2 c.20210G>A or F5 Leiden. Further, the frequency of MTHFR risk allele (T) in patients with maternal age <25 years is marginally significant higher than those in cases with maternal age ≥25 years (p = .069) with an OR of 2.7 (95% CI = 0.90-8.07)., Conclusions: MTHFR is a common susceptibility factor for gastroschisis in Indonesia. The increased gastroschisis risk in offspring of younger maternal age suggests the thrombotic pathogenesis model. A founder effect is the most likely explanation for the rarity of the F2 and F5 Leiden polymorphisms in Indonesian population.

Background: It is estimated that 2 to 35 of newborns present a congenital malformation. Some publications suggest that vascular disruption birth defects are not associated with chromosomal alterations detected by conventional karyotype., Objective: to determine the frequency of chromosomal alterations detected by high resolution G banded karyotype in patients with vascular disruption birth defects in a Colombian population (South America)., Material and Method: transversal study. Population: a sample of patients identified by an epidemiological surveillance system of congenital malformations in a reference hospital in Cali, Colombia., Results: 41 cases of vascular disruption birth defects were identified during a 36 month period; in a descending order those were: transverse reduction defects, hydranencephaly and gastroschisis. Two expert cytogenetists performed independent evaluation of the genetic material of the patients, and no chromosomal alterations detectable by G banded karyotype were identified., Conclusions: It is recommended that genetic counseling in cases of defects by vascular disruption is carried out taking into account the empirical recurrence risks reported for each one the types of defects by vascular disruption and the use of karyotype should be limited to cases with other malformations or chromosomal abnormality suspected by phenotype.

Background: Gastroschisis (GS) is a congenital abdominal wall defect that results in the development of GS-related intestinal dysfunction (GRID). Transforming growth factor-β, a pro-inflammatory cytokine, has been shown to cause organ dysfunction through alterations in vascular and airway smooth muscle. The purpose of this study was to evaluate the effects of TGF-β3 on intestinal smooth muscle function and contractile gene expression., Methods: Archived human intestinal tissue was analyzed using immunohistochemistry and RT-PCR for TGF-β isoforms and markers of smooth muscle gene and micro-RNA contractile phenotype. Intestinal motility was measured in neonatal rats ± TGF-β3 (0.2 and 1 mg/kg). Human intestinal smooth muscle cells (hiSMCs) were incubated with fetal bovine serum ± 100 ng/ml of TGF-β 3 isoforms for 6, 24 and 72 h. The effects of TGF-β3 on motility, hiSMC contractility and hiSMC contractile phenotype gene and micro-RNA expression were measured using transit, collagen gel contraction assay and RT-PCR analysis. Data are expressed as mean ± SEM, ANOVA (n = 6-7/group)., Results: GS infants had increased immunostaining of TGF-β3 and elevated levels of micro-RNA 143 & 145 in the intestinal smooth muscle. Rats had significantly decreased intestinal transit when exposed to TGF-β3 in a dose-dependent manner compared with Sham animals. TGF-β3 significantly increased hiSMC gel contraction and contractile protein gene and micro-RNA expression., Conclusion: TGF-β3 contributed to intestinal dysfunction at the organ level, increased contraction at the cellular level and elevated contractile gene expression at the molecular level. A hyper-contractile response may play a role in the persistent intestinal dysfunction seen in GRID.

We report a case of "mirror-image" gastroschisis in female monochorionic twins. One of the twins presents a right-sided gastroschisis, the other a left-sided gastroschisis. Both twins have anteriorly placed anus and sacral dimple. To the best of our knowledge, this represents the first case of mirror image or discordant left and right gastroschisis in monochorionic twins reported in the literature. This observation may shed further light on the pathogenesis of gastroschisis., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The authors' aim was to detect the associated anomalies and their effect on the management of the fetuses with omphalocele and gastroschisis. Between the period of 2007-2013, the data of fetuses with abdominal wall defects were analyzed. Chromosomal abnormalities and associated morphologic anomalies diagnosed by ultrasonography and autopsy were evaluated. Of the. 61 fetuses, ten (20.4%) omphalocele cases and nine (75%) gastroschisis cases were isolated. Chromosomal abnormalities were found in seven fetuses with omphalocele cases. All fetuses with abnormal karyotypes had multiple additional anomalies. Termination rate was 65.3% for omphalocele group versus none in the gastroschisis group. To give better counseling about the prognosis and outcome of the fetuses with abdominal wall defects, detection of additional anomalies as well as type of the defect are essential tools even if the karyotype is normal.

Maternal smoking during pregnancy is one proposed risk factor for gastroschisis, but reported associations have been modest, suggesting that differences in genetic susceptibility might play a role. We included 108 non-Hispanic white and 62 Hispanic families who had infants with gastroschisis, and 1,147 non-Hispanic white and 337 Hispanic families who had liveborn infants with no major structural birth defects (controls) in these analyses. DNA was extracted from buccal cells collected from infants and mothers, and information on periconceptional smoking history was obtained from maternal interviews, as part of the National Birth Defects Prevention Study. We analyzed five polymorphisms in three genes that code for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1, CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and maternal and infant gene variants, and to assess joint associations of maternal smoking and maternal or infant gene variants with gastroschisis. In analyses adjusted for maternal age at delivery and stratified by maternal race-ethnicity, we identified three suggestive associations among 30 potential associations with sufficient numbers to calculate ORs: CYP1A1*2A for non-Hispanic white mothers who smoked periconceptionally (aOR = 0.38, 95% CI 0.15-0.98), and NAT2*6 for Hispanic non-smoking mothers (aOR = 2.17, 95% CI 1.12-4.19) and their infants (aOR = 2.11, 95% CI 1.00-4.48). This analysis does not support the occurrence of effect modification between periconceptional maternal smoking and most of the xenobiotic metabolizing enzyme gene variants assessed., (© 2014 Wiley Periodicals, Inc.)

A binary vascular/thrombotic pathogenesis for gastroschisis, a form of congenital bowel herniation, is proposed, where normal right umbilical vein involution creates a possible site for thrombosis adjacent to the umbilical ring. If thrombosis occurs, it weakens the area, explaining overwhelmingly right-sided lesions. The model arises from the existence of two groups of risk factors with different maternal age associations. Older mothers show a greater association with vascular factors (although this may actually represent a lack of any significant maternal age effect), consistent with associations of gastroschisis with congenital heart lesions and with amyoplasia. Alternatively, other predispositions, and especially decreased maternal age, the greatest known risk factor, associate with factors raising maternal estrogen, with evidence that estrogen in turn acts here as a predisposition to thrombosis. Absorption of thrombotic by-products from the amniotic fluid can explain the unusual amniocyte inclusions that are common with gastroschisis, while a role for estrogens suggests a connection between rising gastroschisis prevalence and increasing environmental contamination with estrogen disruptors. This model explains a variety of structural and epidemiological findings, and suggests that stratification of data based on binary effects may clarify associated risks and mechanisms. The model also shows that what is often referred to as vascular disruption may actually reflect alternative or additional factors instead, including thrombosis as a primary mechanism., (© 2014 Wiley Periodicals, Inc.)

The most common fetal abdominal wall defects are gastroschisis and omphalocele, both with a prevalence of about three in 10,000 births. Prenatal ultrasound has a high sensitivity for these abnormalities already at the time of the first-trimester nuchal scan. Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas omphalocele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases. Challenges in management of gastroschisis are related to the prevention of late intrauterine death, and the prediction and treatment of complex forms. With omphalocele, the main difficulty is the exclusion of associated conditions, not all diagnosed prenatally. An outline of the postnatal treatment of abdominal wall defects is given. Other rarer forms of abdominal wall defects are pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate anus, spina bifida complex, prune-belly syndrome, body stalk anomaly, and bladder and cloacal exstrophy; they deserve multidisciplinary counselling and management., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Rodent models of abdominal wall defects (AWD) may provide insight into the pathophysiology of these conditions including gut dysfunction in gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis. We further characterise this AWD in Scribble knockout mice., Method: Homozygous Scrib knockout mice were obtained from heterozygote matings. Fetuses were collected at E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed and gut length/weight measured. Ileal specimens were stained for interstitial cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified., Results: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered gut/liver herniation into the umbilical cord. A further 12 exhibited extensive AWD, with eviscerated abdominal organs and thin covering membrane (intact or ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in AWD group compared to controls but morphology/number of ICC was not different., Discussion: The Scribble knockout fetus exhibits exomphalos (intact and ruptured), in contrast to the original published phenotype of gastroschisis. Detailed dissection of fetuses is essential ensuring accurate phenotyping and result reporting., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The etiology of gastroschisis remains elusive. A classic twin study was used to assess the relative contribution of environmental and genetic factors in its development. Screening of 4872 twin pregnancies identified three unreported twin pairs comprising two monozygous and one dizygous discordant pair of twins. Review of the literature identified an additional 21 twin pairs. We observed lower pair- and proband-wise concordance rates for monozygotic compared to dizygotic twin pairs, pair- and proband-wise concordance ratios below 1.0. Our results suggest environmental to play a greater role than genetic factors in the development of gastroschisis.

Background: The AEBP1 (adipocyte enhancer binding protein) gene has two isoforms: AEBP1, the shorter of the two isoforms, and Aclp (aortic carboxypeptidase-like protein). Aclp(-/-) mice demonstrate a ventral wall defect that is similar to gastroschisis in humans. Aclp is a potential candidate gene because it is expressed in numerous tissues during early development in mice; it associates with the extracellular matrix; and is essential for abdominal wall development and wound healing. In contrast, AEBP1 encodes an intracellular protein involved in proinflammatory responses, and may play a critical role in apoptosis and cell survival. Gastroschisis is a severe abdominal wall defect more common in young women and recently associated with a genitourinary infection early in pregnancy., Methods: We screened AEBP1 in 40 cases of gastroschisis and compared identified variants in a control population., Results: We identified several novel variants in AEBP1, including synonymous and nonsynonymous single nucleotide substitutions and intronic indels. However, the frequency of these variants was not significantly different from that of the control group, and the associated amino acid changes were predicted to be benign by two prediction software programs., Conclusions: Gastroschisis remains an intriguing defect that, for an unknown reason, occurs more commonly in young women and after a genitourinary infection. Although we found many alterations in AEBP1 among the gastroschisis cases, they were predicted to be benign. However, this gene requires further understanding of its interaction with other genes involved in the immune response pathway., (Copyright © 2012 Wiley Periodicals, Inc.)

Gastroschisis is a congenital abdominal-wall defect that typically occurs to the right of the umbilicus. Only twenty-one cases of left-sided gastroschisis have been described in the literature. Here we report a large left-sided gastroschisis with pulmonary hypoplasia, scoliosis, ventricular septal defect and absence of gallbladder. Section of placental membranes revealed vacuolization of the amnion, without increased macrophage infiltration of the chorion. Postmortem comparative genomic hybridization micro array did not identify a specific genetic abnormality. Some of the previously reported cases were complicated by additional abnormalities and comparisons with these cases are discussed.

Background: Gastroschisis remains an epidemiologic and pathogenetic dilemma, with genetics not thought to play a significant role in its etiology. The purpose of this study was to determine which gastroschisis cases in the Utah Birth Defect Network (UBDN) were related and the excess familial risk among multigenerational families., Methods: Gastroschisis cases born from 1997 through 2008 were identified from the statewide population-based UBDN and linked with the Utah Population Database (UPDB) to access multigenerational pedigrees. We analyzed these pedigrees using the familial standardized incidence ratio (FSIR)., Results: Of the 284 UBDN gastroschisis cases, one in 40 (n = 7; 2.5%) were reported to have another affected family member. Among these seven cases, three had affected sib pairs and four reported either a distant cousin, paternal uncle, maternal half-uncle, or paternal cousin with gastroschisis. UBDN-UPDB-linked cases resulted in many multigenerational pedigrees with the same affected descendents through marriage. We selected 30 pedigrees for repeated analysis based on two parameters: highest FSIRs with a p ≤ 0.01 and ≥2 cases. In these 30 pedigrees, FSIRs ranged from 3.7 to 93.5 (p < 0.009), each with two to eight distantly related cases (n = 64 distinct cases, representing 23% of the 284)., Conclusions: We found a statistically significant excess risk for gastroschisis because of familial factors. Similar to many other birth defects, gastroschisis may fit a multifactorial model of inheritance. The UBDN-UPDB linkage provides a robust approach to investigating genetic factors. Genetic susceptibility should be further investigated because it may have a greater role in the etiology of gastroschisis than currently appreciated., (Copyright © 2011 Wiley-Liss, Inc.)

Familial cases of isolated abdominal wall defects with variable expressivity in more than one generation have rarely been observed. We report four affected individuals within a small three-generation family with either variable non-syndromic abdominal wall defects or external genital anomalies. We discuss the possible transmission of non-syndromic abdominal wall defects. It could be hypothesized that similar developmental defects may result in anomalies like hypospadias in males or developmental anomalies of the labia minora or labia majora in females., (© 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.)

Gastroschisis and omphalocele are usually considered together since they are both congenital abdominal wall defects, and yet their anatomy, embryogenesis, and clinical presentation and problems are quite different. In addition, it appears that the risk factors for their occurrence differ. Etiologic factors contributing to the development of these defects are unknown. To investigate this we have reviewed reports of risk factors for each anomaly and report them here. We conducted a literature search using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) for risk factors implicated in the development of gastroschisis and omphalocele. The data reviewed here from clinical studies in the literature, closely parallels the data in animal studies which we reported earlier. There is little evidence for a genetic cause in the development of gastroschisis and much evidence supporting the possibility that environmental teratogens are important contributors to the development of this defect. On the other hand, in the case of omphalocele, there was little evidence for environmental factors and substantial data indicating that genetic or familial factors may play an important role.

Vascular mechanisms have been proposed to be involved in the pathogenesis of a number of defects, including transverse-limb defects, intestinal atresias, gastroschisis, hydranencephaly, porencephaly, oromandibular-limb hypogenesis sequence, and oculoauriculovertebral spectrum (OAVS). Here, we examine the available clinical, epidemiologic, and experimental evidence for four defects (transverse-limb defects, intestinal atresias, gastroschisis, and OAVS) for which vascular pathogenesis has been hypothesized. Based on our review, transverse-limb defects appear to sometimes be due to vascular events related to placental vascular abnormalities, hypoperfusion, abnormal development of blood vessels, intrauterine compression, hemoglobinopathies, or exposure to vasoactive agents, although epidemiological studies have not consistently demonstrated the latter association. However, transverse-limb defects can also be due to abnormal developmental events, such as aberrant molecular signaling in the apical ectodermal ridge. Some intestinal atresias may have a vascular origin, with the hypothesis supported by experiments in canines. However, evidence is accumulating that a more common mechanism might be related to improper molecular signaling related to gut specification early in development. In contrast, evidence to support vascular pathogenesis for gastroschisis and OAVS is less compelling. Instead, these defects probably arise from interference with basic developmental events [e.g., body wall closure (gastroschisis) and neural crest cell development (OAVS)]. These conclusions are important for counseling parents of children with these defects and for guiding the design of future epidemiological studies and experiments to further characterize the causes of these defects., (Copyright © 2010 Wiley-Liss, Inc.)

Therapy in newborn infants presents unique challenges. The consequences of exposure of the fetus to medications and environmental contaminants in utero (following the mother's exposure to these) may present, in the newborn, as congenital malformations or adverse drug reactions or have unknown long-term consequences. Risk is not uniformly distributed across a population. Rather, pharmacogenomic principles assert that an individual's unique clinical, genomic, and environmental information can be used to accurately predict predisposition to risk. The challenge is to identify the specific factors--genetic and nongenetic--that contribute to increased risk.

Central and lateral abdominal wall defects are probably distinct and likely arise from different pathogenetic mechanisms. An autopsy study was done using data from a total of 45 central and lateral abdominal wall defect cases to evaluate if they are indeed separate entities and to suggest possible mechanisms involved in their formation. Central defects were found to be statistically different from lateral defects; malformations that co-existed with central defects were mainly bilateral and internal and also involved "inferior" organs in relation to fetal-embryonal blood flow. Patients with lateral defects were more often female, and their coexistent defects were usually unilateral and external, with only 1 defect occurring in an "inferior" organ. These results indicate mechanisms of a vascular perfusion deficit for the majority of the central defects and of external disruption for the lateral defects.

Gastroschisis is a severe major malformation in which an infant is delivered with a portion of intestines and possible other abdominal organs extruding through a defect in the abdominal wall, usually to the right of the umbilical cord. Etiologies of gastroschisis are largely unknown, and even its pathogenesis is poorly understood. Several recent epidemiological studies have identified interactions between maternal smoking during pregnancy, genetic variants of endothelial nitric oxide synthase, and risk for gastroschisis. We present a brief review of the endothelial nitric oxide synthase pathway and its relationship to vasculogenesis, suggesting that disruption of this pathway by environmental exposures or by genetic variation may represent one pathogenetic model for gastroschisis., (Copyright 2008 Wiley-Liss, Inc.)

Background and Methods: A cluster of 10 neonates admitted with a diagnosis of gastroschisis at birth to the Neonatal Intensive Care Unit (NICU) at the University of Kentucky Medical Center in the year 1996, prompted us to perform a retrospective analysis to determine environmental or genetic causes., Results: A total of 36 neonates with gastroschisis were admitted during the period 1/1992 to 12/1996, and the maternal and patient demographics were evaluated by chart review. The mean maternal age was 21.5 years (14-35 years) of which 42% were teenagers, 66% were primiparous, 42% were smokers, 6% had a history of illicit drug use, and 72% had a history of taking prenatal vitamins. Mean birth weight was 2438g (990-3700g) with 54% being preterm with a mean gestational age of 36 wks (29-40 wks). Family history was negative and chromosomes were normal in patients in whom a karyotype was performed (25%). There was no recurring environmental or drug exposure in the study group. The mothers were from 24 different counties of Kentucky. The 36 cases were not uniformly distributed over the five-year period (chi square statistic = 46.8, degrees of freedom = 4, p < 0.0001). However, there was no evidence that the cases clustered in any 1 year (p = 0.99 for Ederer-Myers-Mantel test)., Conclusions: This is one of the few cluster studies of babies born with gastroschisis. Many of the mothers were teenagers, primiparous, and had an increased frequency of smoking. There was no evidence of temporal or spatial clustering in the gastroschisis cases. We conclude that the cluster of gastroschisis cases in our study occurred as a matter of chance.

The etiology of gastroschisis and omphalocele is unclear and their pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with omphalocele and gastroschisis, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 86 patients with omphalocele, 64 (74.4%) had associated malformations. These included patients with chromosomal abnormalities (25, 29.0%); non-chromosomal syndromes including Beckwith-Wiedemann syndrome, Goltz syndrome, Marshall-Smith syndrome, Meckel-Gruber syndrome, Oto-palato-digital type II syndrome, CHARGE syndrome, and fetal valproate syndrome; malformation sequences, including ectopia cordis, body stalk anomaly, exstrophy of bladder, exstrophy of cloaca, and OEIS (Omphalocele, Exstrophy of bladder, Imperforate anus, Spinal defect); malformation complexes including Pentalogy of Cantrell, and non-syndromic multiple congenital anomalies (MCA) (26, 30.2%). Malformations of the musculoskeletal system (31, 23.5%), urogenital system (27, 20.4%), cardiovascular system (20, 15.1%), and central nervous system (12, 9.1%) were the most common other congenital malformations in patients with omphalocele and non-syndromic MCA. Of the 60 patients with gastroschisis, 10 (16.6%) had associated malformations. In contrast to omphalocele, gastroschisis was rarely associated with a complex pattern of malformation, that is, one each (1.7%) with a chromosomal abnormality (trisomy 21), sequence (amyoplasia congenita), unspecified dwarfism, and 7 (11.7%) with MCA. We observed a striking difference in the prevalence of total malformations (74.4% vs. 16.6%, P < 0.001) and specific patterns of malformations associated with omphalocele and gastroschisis which emphasizes the need to evaluate all patients with omphalocele and gastroschisis for possible associated malformations. Malformation surveillance programs should be aware that the malformations associated with omphalocele can be often classified into a recognizable malformation syndrome or pattern (44.2%)., (2008 Wiley-Liss, Inc.)

Objective: Gastroschisis is a congenital malformation characterized by an abdominal wall defect located laterally to a normal umbilicus. The cause of gastroschisis is unknown, but most authors consider it exogenous. We describe the case of a woman with a twin pregnancy in which both twins had gastroschisis., Case Report: A 17-year-old primiparous female was referred to our institution because of a twin pregnancy, with one twin diagnosed with gastroschisis at 34 weeks of gestation. Unfortunately, gastroschisis was noted in both twins, but no other anomalies were observed under level II sonographic evaluation. The twins were delivered by cesarean section at 36+ weeks of gestation because of preterm labor and breech presentation of one fetus. Both twins presented with a 3-cm abdominal wall defect located to the right side of the umbilicus and a large portion of the bowel protruding that was not covered by membrane. Histopathology of the placenta revealed that the twins were diamniotic monochorionic. Chromosomal analysis of cord blood showed normal karyotype (46,XX) in both newborns., Conclusion: The cause of gastroschisis is unknown, although possible exogenous causes have been studied. The diagnosis of gastroschisis in twin pregnancy is always in late gestation. Therefore, maternal serum alpha fetoprotein screening and a detailed prenatal ultrasound evaluation are recommended in multifetal pregnancies.

Objective: To examine the natural history and detailed outcome of antenatally diagnosed abdominal wall defects., Methods: This was a retrospective review of the antenatal reports, pediatric surgery records and subsequent follow-up information of all cases of omphalocele and gastroschisis diagnosed in a 10-year period in our tertiary referral center., Results: There were 109 cases of abdominal wall defects, including omphalocele in 67 cases and gastroschisis in 42 cases. Of the 67 cases of omphalocele there were 26 (39%) with chromosomal abnormalities and 22 (33%) underwent termination of pregnancy, mainly for associated structural abnormalities. Of the ongoing 19 cases there were five (26%) in-utero deaths, 12 (63%) survivors and two (11%) neonatal deaths, both associated with prematurity. Excluding chromosomal abnormalities, the survival rate in isolated omphalocele was 7/16 (44%) whilst it was 5/25 (20%) in those with associated abnormalities. Gastroschisis was isolated in 40 (95%) cases. Among these 40 isolated cases there were two (5%) terminations. Of the 38 ongoing cases, there were two (5%) in-utero deaths, and 36 (95%) live births. Four of the 36 liveborn infants (11%) died in the postoperative period owing to complications of small bowel atresia., Conclusions: Although only 18% of infants with antenatally diagnosed omphalocele were alive in the neonatal period, postoperative morbidity was low. The majority (90%) of fetuses with antenatally diagnosed gastroschisis survived to delivery, but the mortality in affected newborns was 11%., (Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd.)

In recent years, an increase in the rate of gastroschisis has been documented in several countries throughout the world. Based on accumulating evidence that a maternal immunologic response to a novel set of paternal antigens may be involved in risk for several adverse pregnancy outcomes, including preeclampsia, reduced birth weight, and preterm delivery, we tested the hypothesis that a pregnancy following a change in fathers (change in paternity) may be a risk factor for gastroschisis. Using a case-control design, we compared the prevalence of change in paternity with the index pregnancy in 102 mothers of isolated gastroschisis cases to the prevalence of change in paternity in 117 mothers of non-malformed infants and 78 mothers of infants with neural tube defects or oral clefts. In a multivariate analysis, the adjusted odds of change in paternity in multigravid case mothers were 7.81 times higher (95% Confidence interval 2.80-21.88) relative to multigravid mothers of malformed and non-malformed controls combined, after adjustment for maternal age. These data suggest that maternal immune factors may play a role in the cause of gastroschisis. Further research is needed to corroborate these findings and to elucidate possible immunologic mechanisms involved in the pathogenesis of gastroschisis.

Gastroschisis, a ventral body wall defect, is a continuing challenge and concern to researchers, clinicians, and epidemiologists seeking to identify its cause(s) and pathogenesis. Concern has been renewed in recent years because, unlike most other birth defects, rates of gastroschisis are reportedly increasing in many developed and developing countries. No tenable explanation or specific causes have been identified for this trend. Rates of gastroschisis are particularly high among pregnancies of very young women. Such an intriguing association, not observed to this degree with other birth defects, may afford clues to the defect's cause. Understanding the causes of gastroschisis may provide insight to the defect's origin. In pursuing such causal studies, it would be helpful to understand the embryogenesis of gastroschisis. To date, four main embryologic hypotheses have been proposed: (1) Failure of mesoderm to form in the body wall; (2) Rupture of the amnion around the umbilical ring with subsequent herniation of bowel; (3) Abnormal involution of the right umbilical vein leading to weakening of the body wall and gut herniation; and (4) Disruption of the right vitelline (yolk sac) artery with subsequent body wall damage and gut herniation. Although based on embryological phenomena, these hypotheses do not provide an adequate explanation for how gastroschisis would occur. Therefore, we propose an alternative hypothesis, based on well described embryonic events. Specifically, we propose that abnormal folding of the body wall results in a ventral body wall defect through which the gut herniates, leading to the clinical presentation of gastroschisis. This hypothesis potentially explains the origin of gastroschisis as well as that of other developmental defects of the ventral wall.

Objectives: To describe the molecular analysis through comparative genomic hybridization (CGH) of fetuses with gastroschisis, and to observe if this technique could improve the resolution of the conventional cytogenetic techniques., Methods: Amniotic analysis of fetuses with gastroschisis, using both conventional (G-banding) and molecular (CGH) cytogenetics assays., Results: All of the seven fetuses studied displayed a normal G-band karyotype. Six fetuses displayed a normal disomic profile through CGH and one sample has displayed ish cgh enh 3q26-->qter result (ICSN). The fetus with this imbalance of chromosome 3 was re-classified as a ruptured omphalocele, instead of gastroschisis, after birth., Conclusions: The molecular investigation through CGH technique can improve the resolution of the conventional karyotye analysis in cases of abdominal wall defects., (Copyright 2007 S. Karger AG, Basel.)

Gastroschisis is a rare anomaly and it is usually not associated with other syndromic or nonsyndromic anomalies. The first case of gastroschisis with aneuploidy (Turner syndrome) is presented. A fetal huge cystic hygroma was diagnosed by prenatal sonography at 12 weeks of pregnancy and chorionic villi sampling (CVS) was performed. Cytogenetic analysis revealed 45, X0. The pregnancy was terminated by induction of labor at 16 weeks of pregnancy. The female fetus had a big membrane of cystic hygroma surrounding the fetal neck. Additionally, a full abdominal thickness defect with multiple loops of bowel outside the abdomen, which could not be diagnosed on prenatal ultrasound scan, was detected on postnatal examination., (Copyright (c) 2007 S. Karger AG, Basel.)

Background: Incorporating genetic analyses into birth defect cluster investigations may increase understanding of both genetic and environmental risk factors for the defect. Current constraints of most birth defect cluster investigations make candidate gene selection the most feasible approach. Here, we describe strategies for choosing candidate genes for such investigations, which will also be applicable to more general gene-environment studies., Methods: We reviewed publicly available web-based resources for selection of candidate genes and identification of risk factors, as well as publications on different strategies for candidate gene selection., Results: Candidate gene selection requires consideration of available gene-disease databases, previous epidemiological studies, animal model research, linkage and expression studies, and other resources. We describe general considerations for utilizing available resources, as well as provide an example of a search for candidate genes related to gastroschisis., Conclusions: Available web resources could facilitate selection of candidate genes, but selection of optimal candidates will still require a strong understanding of genetics and the pathogenesis of the defect, as well as careful consideration of previous epidemiological studies.

Background: Gastroschisis is a severe birth defect in which the infant is born with a portion of the intestines extruding through a small tear in the abdominal wall, usually to the right of the umbilical cord. Its etiology is unknown, but the prevailing hypothesis is that it results from a vascular accident at the time of involution of the right umbilical vein or of the development of the superior mesenteric artery., Methods: In a case-control study of 57 cases of gastroschisis and 506 controls, we tested DNA for polymorphisms of 32 genes representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength., Results: In logistic regression, controlling for maternal ethnicity, and using the homozygote wild-type as referent, the following gene polymorphisms were associated with an increased risk for a gastroschisis for heterozygotes: ICAM1 gly241arg (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 -3.4); NOS3 glu298asp (OR, 1.9; 95% CI, 1.1-3.4); NPPA 2238T > C (OR, 1.9; 95% CI, 1.0-3.4); and ADD1 gly460trp (OR, 1.5; 95% CI, 0.8-2.8). Additionally, for the NPPA and ADD1 single-nucleotide polymorphisms (SNPs), the homozygote variants had a significantly higher risk than the heterozygotes (OR, 7.5; 95% CI, 1.7-33.5 and OR, 4.9; 95% CI, 1.9-12.9, respectively). Three SNPs showed a strong interaction with maternal smoking. The risk for smokers with 1 or 2 variant alleles compared to nonsmokers with the wild-type allele were: NOS3 (OR, 5.2; 95% CI, 2.4-11.4); ICAM1 (OR, 5.2; 95% CI, 2.1-12.7); and NPPA (OR, 6.4; 95% CI, 2.8-14.6)., Conclusions: These results support the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors., ((c) 2006 Wiley-Liss, Inc.)

The congenital malformation gastroschisis has a genetic disposition in the inbred mouse strain HLG/Zte. It is increased after preconceptional irradiation of males or females. Radiation exposures during the meiotic stages are most efficient. This malformation can also be induced by ionising radiation when the exposure takes place during the preimplantation period especially during the zygote stage. This latter effect can be transmitted to the next mouse generation. Other macroscopically visible or skeletal malformations are not significantly induced under these experimental conditions. These latter malformations are increased by radiation exposures during major organogenesis. The mechanisms for the development of the effects are different. Radiation exposure of the mouse zygote (1 to 3 hours p.c.) also leads to the induction of genomic instability in skin fibroblasts of the fetus. This phenomenon also occurs in a mouse strain (C57BL/6J) which is not susceptible to radiation-induced gastroschisis during the preimplantation period. The genomic instability is transmitted to the next mouse generation. During genomic instability chromatide breaks are dominating as in non-exposed cells. With respect to "spontaneous" malformations gastroschisis is dominating in HLG/Zte mice. Late radiation effects seem to have similar patterns as observed in non-exposed subjects, however, the rates are increased after irradiation.

Objective: Occlusion of the omphalomesenteric artery in utero, leading to disruption of the umbilical ring with subsequent herniation of intestines, has been proposed as the mechanism by which gastroschisis occurs. We hypothesized that affected fetuses have a predisposition to arterial or venous thromboembolism., Study Design: Thirty-one children born with gastroschisis were tested for Factor V Leiden, prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations. Fifty-two appropriately grown term neonates whose mothers were matched by maternal age and race served as control neonates., Results: Of children with gastroschisis, 6.45% were heterozygous for Factor V Leiden. No infants with gastroschisis had prothrombin gene mutations. Thirty-six percent of affected infants were heterozygous, and 16% were homozygosity for MTHFR. Among control infants, 42% were heterozygous, and 14% were homozygous for MTHFR., Conclusion: The mutation rate for MTHFR did not differ in children with and without gastroschisis when mothers were matched by race and age.

The etiology of gastroschisis is still unclear. To the authors' knowledge, there are only 14 cases of familial gastroschisis in the literature. The authors add the second case of mother-and-son occurrence and a case of siblings occurrence, thereby updating the current literature for family gastroschisis.