Failure of normal closure of the anterior abdominal wall can result in a number of defects, most commonly gastroschisis, omphalocele, and cloacal exstrophy. Any of these defects will result in elevated alpha-fetoprotein, and they are second only to CNS anomalies as a cause of elevated AFP.

Omphalocele, the most common, occurs in 1 in 4,000 live births. Due to failure of fusion of the lateral folds, it results in a midline defect in which bowel, liver, or a combination herniate into the base of the umbilical cord. Embryologically, it is thought that the larger defects, which include the liver, are due to a failure of primary abdominal wall closure. Smaller defects, involving only bowel, likely represent a failure of complete midgut rotation with persistence of the primitive body stalk. Chromosomal abnormalities are more common when the sac contains only bowel (67%), as opposed to the 16% incidence of chromosomal abnormalities when the sac contains liver.

Omphaloceles always demonstrate herniated contents covered by an amnioperitoneal sac. The umbilical cord usually inserts into the anterior portion of the defect, though it may also insert laterally. Up to 2/3 of patients with omphalocele have associated anomalies, including trisomies. The mean incidence of trisomies is 12%, with 30-50% of patients having complex cardiac defects. While it is rare for these patients to have Beckwith-Wiedemann syndrome, 5-10% of patients with Beckwith-Wiedemann also have omphalocele.

Gastroschisis, occurring in 1/10,000, demonstrates a defect lateral to midline, usually in the right lower quadrant. The herniated contents are seen as free-floating bowel, without a covering membrane, and the umbilical cord inserts normally. The exposure of the bowel to amniotic fluid results in dysmotility, and as infants these patients often present with pseudoobstruction. These cases are usually sporadic.

Less common than the previous entities, cloacal exstrophy involves bladder exstrophy, omphalocele, and epispadias, with concomitant diastasis of the pubic bones and spinal disraphism.