IFG2R is responsible for degradation of excess IGF-2 protein. BWS disease is caused by a mutation in chromosome 11 at the locus where the IGF2 gene resides. Observance of the inheritance patterns of the associated anomalies through pedigrees show that exomphalos can be the result of autosomal dominant, autosomal recessive and X-linked inheritance. Environmental factors
It is not well known if actions of the mother could predispose or cause the disease. Alcohol use during the first trimester, heavy smoking, use of certain medications like the selective serotonin-reuptake inhibitors and methimazole (anti-thyroid drug) during pregnancy, maternal febrile illness, IVF, parental consanguinity and obesity elevate the risk of a woman giving birth to a baby with exomphalos. Preventive methods that could be utilised by mothers include ingestion of a preconception multivitamin and supplementation with folic acid. Termination of pregnancy may be considered if a large exomphalos with associated congenital abnormalities is confirmed during prenatal diagnosis. Diagnosis
Related conditions
Gastroschisis is a similar birth defect, but in gastroschisis the umbilical cord is not involved and the intestinal protrusion is usually to the right of the midline. Parts of organs may be free in the amniotic fluid and not enclosed in a membranous (peritoneal) sac. Gastroschisis is less frequently associated with other defects than omphalocele.Omphaloceles occurs more frequently with increased maternal age. Other related syndromes are Shprintzen Goldberg, pentalogy of Cantrell, Beckwith–Wiedemann and OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects).After surgery a child with omphalocele will have some degree of intestinal malrotation.
In the disease the muscle undergoes normal differentiation but fails to expand ventro-medially and narrow the umbilical ring which causes the natural umbilical hernia that occurs at 6 weeks of gestation to remain external to the body.The location of the folding defect in the embryo determines the ultimate position of the exomphalos. A cephalic folding defect results in an epigastric exomphalos that is positioned high up on the abdomen which can be seen in the chromosomal defect pentalogy of Cantrell. Lateral folding defects result in a typical exomphalos that is positioned in the middle of the abdomen. A caudal folding defect results in a hypogastric exomphalos that is positioned on the lower abdomen. Genetics
The genes that cause exomphalos are controversial and subject to research. Exomphalos is greatly associated with chromosomal defects and thus these are being explored to pinpoint the genetic cause of the disease. Studies in mice have indicated that mutations in the fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) cause exomphalos. Fibroblast growth factor (FBGF) encourages the migration of myotubules during myogenesis. When FBGF runs out myoblasts stop migrating, cease division and differentiate into myotubules that form muscle fibers. Mutations in homeobox genes such as Alx4, that direct the formation of body structures during early embryonic development cause exomphalos in mice. Mutations in the Insulin like growth factor-2 gene (IGF2) and its associated receptor gene IGF2R cause high levels of IGF-2 protein in humans which leads to exomphalos in the associated disease Beckwith Wiedemann syndrome (BWS).