An omphalocele or omphalocoele, also known as an exomphalos, is a rare abdominal wall defect. Beginning at the 6th week of development, rapid elongation of the gut and increased liver size reduces intra abdominal space, which pushes intestinal loops out of the abdominal cavity. Around 10th week, the intestine returns to the abdominal cavity and the process is completed by the 12th week. Persistence of intestine or the presence of other abdominal viscera (e.g.

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

) in the umbilical cord results in an omphalocele. Omphalocele occurs in 1 in 4,000 births and is associated with a high rate of mortality (25%) and severe malformations, such as cardiac anomalies (50%), neural tube defect (40%), exstrophy of the bladder and Beckwith–Wiedemann syndrome. Approximately 15% of live-born infants with omphalocele have chromosomal abnormalities. About 30% of infants with an omphalocele have other congenital abnormalities.

Signs and symptoms

The sac, which is formed from an outpouching of the

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...

, protrudes in the midline, through the umbilicus (navel). It is normal for the intestines to protrude from the abdomen, into the umbilical cord, until about the tenth week of

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

, after which they return to inside the fetal abdomen. The omphalocele can be mild, with only a small loop of intestines present outside the abdomen, or severe, containing most of the abdominal organs. In severe cases surgical treatment is made more difficult because the infant's abdomen is abnormally small, having had no need to expand to accommodate the developing organs. Larger omphaloceles are associated with a higher risk of cardiac defects.

Complications

Complications may occur prenatally, during birth, management, treatment or after surgery. Both prenatally and during birth, the exomphalos can rupture. During birth there may be trauma to the liver for giant omphaloceles. During management exomphalos can act as a metabolic drain affecting nitrogen balance which can lead to failure to thrive, as well as

hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

. Use of a non-absorbent patch during surgery can lead to wound

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

post-surgery.

Hernia A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal Devel ...

tion from the patch is also a possibility. Intestinal dysfunction for a few weeks after the surgery is common, therefore parenteral feeding is continued post-surgery, however prolonged use of this may lead to

hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...

and cholestasis. If intestinal dysfunction persists it can lead to intestinal

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

. Intestinal atresia can occur, which is where the mucosa and submucosa of the intestine form a web that obstructs the lumen which leads to malabsorption. Obstruction of the bowel can occur which results in short bowel syndrome. For the first few years of life there is a high incidence of gastroesophageal reflux which can be complicated by oesophagitis. Post-surgery the umbilicus (

navel The navel (clinically known as the umbilicus; : umbilici or umbilicuses; also known as the belly button or tummy button) is a protruding, flat, or hollowed area on the abdomen at the attachment site of the umbilical cord. Structure The u ...

) is deficient or abnormally placed that causes dislike amongst many patients. Umbilical reconstruction can be difficult due to scar tissue and lack of extra skin for surgical use, though this can be overcome by using tissue expanders below the skin and umbilicoplasty. Ultimately,

prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...

depends on the size of the defect and whether associated abnormalities are present or complications develop. Mortalities and morbidities still occur, with the

mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular Statistical population, population, scaled to the size of that population, per unit of time. Mortality rate is typically ...

for large omphaloceles with associated abnormalities being higher. Most surviving omphalocele infants have no-long-term problems and grow up to be normal individuals. Omphalocele awareness ribbon

Causes

Omphalocele is caused by malrotation of the bowels while returning to the abdomen during development. Some cases of omphalocele are believed to be due to an underlying genetic disorder, such as Edward's syndrome (trisomy 18) or Patau syndrome (trisomy 13). Beckwith–Wiedemann syndrome is also associated with omphaloceles.

Pathophysiology

Exomphalos is caused by a failure of the

ventral Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...

body wall to form and close the naturally occurring

umbilical hernia An umbilical hernia is a health condition where the abdominal wall behind the navel is damaged. It may cause the navel to bulge outwards—the bulge consisting of abdominal fat from the greater omentum or occasionally parts of the small intestine. ...

that occurs during embryonic folding which is a process of

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

. The normal process of

is that at 2 weeks gestation the human embryo is a flat disc that consists of three layers, the outer

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...

and inner

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gastr ...

separated by a middle layer called the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

. The

gives rise to skin and the CNS, the

gives rise to muscle and the

gives rise to organs. The focus areas for exomphalos are that the

will form the umbilical ring, the

will form the abdominal muscles and the

will form the gut. After the disc becomes tri-layered, it undergoes growth and folding to transform it from disc to cylinder shaped. The layer of

and

in the dorsal axis grow ventrally to meet at the midline. Simultaneously, the cephalic (head) and caudal (tail) ends of these layers of the disc fold ventrally to meet the lateral folds in the center. The meeting of both axis at the center form the umbilical ring. Meanwhile, the endoderm migrates to the center of this cylinder. By the fourth week of

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregn ...

the umbilical ring is formed. During the 6th week the

midgut The midgut is the portion of the human embryo from which almost all of the small intestine and approximately half of the large intestine develop. After it bends around the superior mesenteric artery, it is called the "midgut loop". It comprises ...

rapidly grows from the

which causes a

hernia A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal Devel ...

tion of the gut through the umbilical ring. The gut rotates as it re-enters the

abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contain Organ (anatomy), organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roo ...

which allows for the

small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

and colon to migrate to their correct anatomical position by the end of the 10th week of development. This process fails to occur normally in cases of exomphalos, resulting in abdominal contents protruding from the umbilical ring. Gut contents fail to return to the abdomen due to a fault in

myogenesis Myogenesis is the formation of skeletal muscle, skeletal muscular tissue, particularly during embryonic development. Skeletal muscle#Skeletal muscle cells, Muscle fibers generally form through the fusion of precursor cell, precursor myoblasts in ...

(muscle formation and migration during

). During

the

that forms muscle divides into several

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...

s that migrate dorso-ventrally towards the midline. The somites develop three parts that are

sclerotome The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...

which will form bone,

dermatome Dermatome may refer to: * Dermatome (anatomy), an area of skin that is supplied by a single pair of dorsal roots * Dermatome (embryology), the portion of the embryonic paraxial mesoderm, the somite, which gives rise to dermis * Dermatome (instrument ...

which will form skin of the back and myotome which will form muscle. The

s that remain close to the neural tube at the back of the body have epaxial myotome, whilst the

s that migrate to the midline have hypaxial myotome. The hypaxial myotome forms the abdominal muscles. The myotome cells will give rise to myoblasts (embryonic

progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only diffe ...

s) which will align to form myotubules and then muscle fibers. Consequently, the myotome will become three muscle sheets that form the layers of abdominal wall muscles. The muscle of concern for exomphalos is the

rectus abdominis The rectus abdominis muscle, () also known as the "abdominal muscle" or simply better known as the "abs", is a pair of segmented skeletal muscle on the ventral aspect of a person, person's abdomen. The paired muscle is separated at the midline b ...

. In the disease the muscle undergoes normal differentiation but fails to expand ventro-medially and narrow the umbilical ring which causes the natural

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 The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...

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

. 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

. When FBGF runs out myoblasts stop migrating, cease division and differentiate into myotubules that form muscle fibers. Mutations in

homeobox A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of ...

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). '' 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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

and X-linked inheritance.

Environmental factors

It is not well known if actions of the mother could predispose or cause the disease.

Alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

use during the first trimester, heavy

smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...

, use of certain

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

s like the selective serotonin-reuptake inhibitors and methimazole (anti-thyroid drug) during pregnancy, maternal febrile illness, IVF, parental

consanguinity Consanguinity (from Latin '':wikt: consanguinitas, consanguinitas'' 'blood relationship') is the characteristic of having a kinship with a relative who is descended from a common ancestor. Many jurisdictions have laws prohibiting people who are ...

and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

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 Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

. Termination of pregnancy may be considered if a large exomphalos with associated congenital abnormalities is confirmed during prenatal diagnosis.

Diagnosis

Related conditions

Gastroschisis Gastroschisis is a birth defect in which the baby's intestines extend outside of the abdomen through a hole next to the belly button. The size of the hole is variable, and other organs including the stomach and liver may also occur outside the b ...

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 A cloaca ( ), : cloacae ( or ), or vent, is the rear orifice that serves as the only opening for the digestive (rectum), reproductive, and urinary tracts (if present) of many vertebrate animals. All amphibians, reptiles, birds, cartilagin ...

, imperforate anus, spinal defects). After surgery a child with omphalocele will have some degree of intestinal malrotation. Due to intestinal malrotation 4.4% of children with omphalocele will experience a midgut volvulus in the days, months, or years after surgery. Parents of children with omphalocele should seek immediate medical attention if their child displays signs and symptoms of an intestinal obstruction at any point in their childhood to avoid the possibility of bowel necrosis or death. Some experts differentiate exomphalos and omphalocele as 2 related conditions, one worse than the other; in this sense, exomphalos involves a stronger covering of the hernia (with fascia and skin), whereas omphalocele involves a weaker covering of only a thin membrane. Others consider the terms synonymous names for any degree of herniation and covering.

Screening

An omphalocele is often detected through AFP screening or a detailed fetal

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

. Genetic counseling and

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

such as amniocentesis are usually offered during the pregnancy.

Management

There is no treatment that is required prenatally unless there is a rupture of the exomphalos within the mother. An intact exomphalos can be delivered safely vaginally and C-sections are also acceptable if obstetrical reasons require it. There appears to be no advantage for delivery by C-section unless it is for a giant exomphalos that contains most of the

. In this case vaginal delivery may result in dystocia (inability of the baby to exit the pelvis during birth) and liver damage. Immediately after birth a nasogastric tube is required to decompress the intestines and an endotracheal intubation is needed to support respiration. The exomphalos sac is kept warm and covered with a moist saline gauze and plastic transparent bowel bag to prevent fluid loss. The

neonate In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

also requires fluid,

vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...

and

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

administration intravenously. After management strategies are applied, a baby with an intact sac is medically stable and does not require urgent surgery. This time is used to assess the

newborn In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

to rule out associated anomalies prior to surgical closure of the defect. Studies show there is no significant difference in survival between immediate or delayed closure. Surgery can be performed directly for small omphaloceles, which will require a short stay in the nursery department, or in a staged manner for large omphaloceles, which will require several weeks stay. Staged closure requires a temporary artificial holding sac (a silo) to be placed over the abdominal organs and sutured to the abdominal wall. This can be made of non-adhesive dressing. The silo is gradually reduced in size at least once daily until all of the

viscera In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...

have been returned to the

. This is repeated for several days to a week until surgical closure of the

fascia A fascia (; : fasciae or fascias; adjective fascial; ) is a generic term for macroscopic membranous bodily structures. Fasciae are classified as superficial, visceral or deep, and further designated according to their anatomical location. ...

/skin can be done. Closure may require a patch that can be rigid or non-rigid and made of natural

biomaterial A biomaterial is a substance that has been Biological engineering, engineered to interact with biological systems for a medical purpose – either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a Medical diag ...

s such as a bovine

pericardium The pericardium (: pericardia), also called pericardial sac, is a double-walled sac containing the heart and the roots of the great vessels. It has two layers, an outer layer made of strong inelastic connective tissue (fibrous pericardium), ...

or artificial materials. The skin is then closed over the patch and it is re-vascularised by the body's

blood vessels post-surgery. The staged surgery is required, as rushed reduction of the exomphalos compromises venous return and ventilation, as it raises intra-abdominal pressure. In some cases, stretching of the abdominal wall to accommodate intestinal contents may be required. Non-operative therapy uses

eschar Eschar (; ; ; or ''an'' eschar) is a slough or piece of necrosis, dead tissue that is cast off from the surface of the skin, particularly after a Burn, burn injury, but also seen in gangrene, Ulcer (dermatology), ulcer, mycosis, fungal infection ...

otic ointments. This is used for infants with large omphaloceles that have been born prematurely with respiratory insufficiency and associated chromosomal defects, as they would not be able to tolerate surgery. The ointment causes the sac to granulate and epithelialize, which leaves a residual large

, which can be repaired later with surgery when the baby is more stable. After surgery, for larger omphaloceles,

mechanical ventilation Mechanical ventilation or assisted ventilation is the Medicine, medical term for using a ventilator, ventilator machine to fully or partially provide artificial ventilation. Mechanical ventilation helps move air into and out of the lungs, wit ...

and parenteral nutrition is needed to manage the baby.

Society and culture

Awareness Day

International Omphalocele Awareness Day is celebrated annually in the US on January 31, as part of Birth Defect Awareness Month. Several U.S. states have passed resolutions to officially recognize the date.

References

Omphalocele Diagnosis and Treatment at SSM Health St. Louis Fetal Care Institute

at

Brown University Brown University is a Private university, private Ivy League research university in Providence, Rhode Island, United States. It is the List of colonial colleges, seventh-oldest institution of higher education in the US, founded in 1764 as the ' ...

Fetal Treatment Center: Omphalocele
at

UCSF The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California, United States. It is part of the University of California system and is dedicated entirely to health science and life ...

Gastroschisis Exomphalos Extrophies Parent Support (GEEPS)
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External links

{{Congenital abdominal wall defects Abdominal wall defects Congenital disorders of musculoskeletal system Genetic disorders with OMIM but no gene