Gastroschisis and omphalocele (also referred to as exomphalos) are 2 of the most common abdominal wall defects requiring neonatal intensive care. Their similarities, most notably evisceration of abdominal structures through a defect at or near the umbilicus, misled generations of physicians and surgeons to inaccurately diagnose them as a single common disease. The pathologic differences between these 2 entities were formally realized when, in 1953, Thomas Moore and George Stokes defined gastroschisis as a large extraumbilical evisceration of intestines without a covering sac. They distinguished this from omphalocele, which was defined as the herniation of viscera into the base of the umbilical cord with a protective membranous sac.1 The establishment of gastroschisis and omphalocele as 2 distinct pathologies with their own specific anatomic features and associated anomalies provides the basis for our management of these defects today.
Historically, omphalocele was observed nearly twice as commonly as gastroschisis. More recent literature shows an increase in the incidence of gastroschisis,2, 3, and 4 suggesting that the actual relationship is approximately 1:1. This phenomenon remains unexplained but is probably related to a combination of improved diagnostic coding (prior to the incorporation of Moore and Stokes's definition, gastroschisis was commonly referred to as omphalocele) and the environmental factors noted in the discussion that follows. The approximate incidence is 1–3 per 10,000 live births for both gastroschisis and omphalocele.4
Population studies have found associations between a number of environmental factors and gastroschisis. Young maternal age (<20 years) reproducibly correlates with gastroschisis, while individual studies have found gastroschisis to be associated with low economic status, maternal use of over-the-counter vasoactive medications or salicylates, maternal smoking, alcohol consumption, and illicit substance use.2, 5, 6, 7, and 8 Omphalocele, on the other hand, is associated with advanced maternal age and karyotype abnormalities.5, 7, 9
The genetic basis for gastroschisis is poorly understood. Gastroschisis is most frequently sporadic, but there are rare familial cases documented in the literature, suggesting an underlying genetic component. Such case reports include concordance for gastroschisis in monozygotic twins,10, 11 dizygotic twins,12 and distant relatives.13
Genotype analysis of patients with gastroschisis has led to the identification of associated single-nucleotide polymorphisms (SNPs) at the genes encoding endothelial nitric oxide synthase (NOS3/eNOS; odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.4); intracellular adhesion molecule 1 (ICAM1; OR 1.9, 95% CI 1.1–3.4); and atrial natriuretic peptide precursor α (NPPA; OR 1.9, 95% CI 1.0–3.4).14 Both ICAM and NOS3/eNOS are intimately involved in the molecular cascades of angiogenesis.15 Although inconclusive, these studies lend some weight to the vasculogenic theories of pathogenesis discussed in the following section. Interestingly, when these polymorphisms were analyzed in mothers who smoked during pregnancy, the odds ratio for developing gastroschisis increased substantially (NOS3/eNOS OR 5.2, 95% CI 2.4–11.4; ICAM1 OR 5.2, 95% CI 2.1–12.7; NPPA OR 6.4, CI 2.8–14.6), providing evidence for a gene-environment interaction.14
Omphalocele, in comparison, is associated with significant chromosomal abnormalities in approximately ...