Gastroschisis is a congenital defect of the abdominal wall that occurs laterally to, and often to the right of, a normally closed umbilical ring. Visceral organs that herniate through the defect are not covered by a membrane. Gastroschisis ... Gastroschisis is a congenital defect of the abdominal wall that occurs laterally to, and often to the right of, a normally closed umbilical ring. Visceral organs that herniate through the defect are not covered by a membrane. Gastroschisis is distinct from omphalocele (164750), which is characterized by herniation of abdominal contents through the base of the umbilical cord; in omphalocele, the visceral organs are covered by membranes (summary by Mastroiacovo et al., 2007). Both omphalocele and gastroschisis, when they occur without other malformations, are probably multifactorial (Baird and MacDonald, 1981).
Occurrence of gastroschisis in sibs was reported by Salinas et al. (1979) and by Lowry and Baird (1982). Hershey et al. (1989) described 2 families with multiple sibs with abdominal wall defects. In the first family, normal parents ... Occurrence of gastroschisis in sibs was reported by Salinas et al. (1979) and by Lowry and Baird (1982). Hershey et al. (1989) described 2 families with multiple sibs with abdominal wall defects. In the first family, normal parents gave birth to identical (monochorionic, diamniotic twins) with gastroschisis. In the second family, a normal mother gave birth to a son with omphalocele and later, by a different husband, to a stillborn girl with partial atresia of the colon and a liveborn girl with gastroschisis. In neither case were there associated anomalies. The experience suggests that some cases of gastroschisis and omphalocele may have the same genetic basis. From a population-based study of omphalocele and gastroschisis, Yang et al. (1992) concluded, however, that the two are distinct. They also found differences according to whether each was an isolated defect or was associated with multiple other birth defects. More than 50% of infants with omphalocele had additional defects, but only about 15% of those with gastroschisis do. An autosomal recessive model of inheritance was found to be the most parsimonious explanation for the families of infants with isolated omphalocele or gastroschisis. Torfs and Curry (1993) found only 6 published reports of familial occurrence of gastroschisis. They reported on a population-based evaluation of familial occurrence. In California, the prevalence of gastroschisis was estimated to be about 2/10,000 births and to be highest in the youngest mothers, rarely occurring in mothers more than 30 years of age. Males were more frequently affected than females; M/F = 1.5. In an investigation of the families of 127 cases, they found 6 (4.7%) in which there was 1 affected relative. The relationships of the affected were: sib, half sib (2), first cousin, second cousin once removed, and great uncle. Sib recurrence was 3.5%. Bugge et al. (1994) described a pair of monozygotic female twins discordant for gastroschisis. Zygosity was verified by DNA analysis using highly polymorphic microsatellites. They found reports of 8 instances of recurrence of gastroschisis in 2 sibs. In 2 separate reports, gastroschisis occurred in half sibs with different fathers. In 2 other reports, gastroschisis occurred in cousins. In a report on 274 cases of gastroschisis registered in 21 regional registers in Europe (EUROCAT registers) during the period 1980-1990, Calzolari et al. (1995) gave a prevalence rate for gastroschisis of 0.94 per 10,000. Gastroschisis was an isolated malformation in 79% of cases. Prenatal diagnosis leading to termination of pregnancy was reported in 26.5% of gastroschisis cases. On the basis of clinical manifestations, epidemiologic characteristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition. Feldkamp et al. (2007) reviewed the evidence for a genetic basis for gastroschisis, animal models of gastroschisis, and various embryologic hypotheses that have been proposed, including failure of the mesoderm to form in the body wall, rupture of the amnion around the umbilical ring, abnormal involution of the right umbilical vein, and disruption of the right vitelline artery. Feldkamp et al. (2007) proposed an alternative hypothesis based on well-described embryonic events, specifically the abnormal folding of the body wall resulting in a ventral body wall defect through which the gut herniates, leading to the clinical presentation of gastroschisis. The authors noted that this hypothesis potentially explains the origin of gastroschisis, as well as that of other developmental defects of the ventral wall. Chambers et al. (2007) compared the prevalence of change in paternity with the index pregnancy in 102 mothers of isolated gastroschisis cases to that of 117 mothers of nonmalformed infants and 78 mothers of infants with neural tube defects or oral clefts. Multivariate analysis revealed that the adjusted odds of change in paternity in multigravid mothers of gastroschisis cases were 7.81 times higher relative to multigravid mothers of malformed and nonmalformed controls combined, after adjustment for maternal age. Chambers et al. (2007) suggested that maternal immune factors may play a role in gastroschisis. Mastroiacovo et al. (2007) analyzed 3,322 cases of gastroschisis from 24 birth defect registries worldwide and found that 469 (14.1%) cases were registered as 'nonisolated,' including 41 chromosomal syndromes, 24 other syndromes, and 404 multiple congenital anomalies (MCA). Among MCA cases, 4 groups of anomalies were most frequent: CNS (4.5%), cardiovascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). Two patterns emerged, with 26 MCA cases resembling limb-body wall complex (see 217100) and 26 others resembling the omphalocele-exstrophy-imperforate anus-spinal defects complex (OEIS; 258040); in both situations, omphalocele rather than gastroschisis is more commonly reported, and the authors noted that these cases may represent misdiagnoses of the abdominal wall defect. Combining their review with other published reports, Mastroiacovo et al. (2007) stated that the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%.
In a case-control study of 57 gastroschisis cases and 506 controls, Torfs et al. (2006) analyzed DNA for polymorphisms in 32 genes encoding enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal/epidermal strength. Logistic regression ... In a case-control study of 57 gastroschisis cases and 506 controls, Torfs et al. (2006) analyzed DNA for polymorphisms in 32 genes encoding enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal/epidermal strength. Logistic regression analysis controlling for maternal ethnicity and using the homozygote wildtype as referent revealed 3 SNPs in the ICAM1 (147840), NOS3 (163729), and NPPA (108780) genes that were significantly associated with an increased risk for gastroschisis for heterozygotes (G241R, OR = 1.7; E298D 163729.0001, OR = 1.9; 2238T-C, OR = 1.9, respectively). The 3 SNPs showed a strong interaction with maternal smoking (OR, 5.2 to 6.4) for smokers carrying 1 or 2 variant alleles compared to wildtype nonsmokers. Torfs et al. (2006) stated that, because of the exploratory design of their study, the results should be considered preliminary, but they support the hypothesis of vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors. Lammer et al. (2008) reviewed the evidence supporting a gene-environment model of gastroschisis involving the VEGF (192240)-NOS3 pathway.