Firm Rounds

Robert Listernick, MD, and colleagues discuss hard-to-diagnose cases.

Newborn with an Omphalocele and Ventricular Septal Defect

Robert Listernick, MD

his baby boy was the 4,465-gram product of a 37-week gestation to a 39-year-old G2P2 female. The pregnancy was complicated by ultrasonography that revealed an omphalocele as well as ventricular septal defect and possible tetralogy of Fallot. Prenatal surgical consultation was obtained. Robert Listernick, MD, moderator: Just to be clear, whats the difference between an omphalocele and gastroschisis? Marleta Reynolds, MD, pediatric surgeon: Omphalocele is a defect of the abdominal wall due to failure of fusion of the umbilical ring. Intestinal contents herniate through the defect covered by a sac, unless it has ruptured. Theres a high incidence of associated extraintestinal defects. In gastroschisis, the defect is always to the right of an intact umbilicus. It results from rupture of a dysplastic abdominal wall or a vascular defect. There is neither a sac nor any associated defects. Dr. Listernick: What issues should be addressed at this prenatal consultation?

Kathy Barsness, MD, pediatric surgeon: We need to discuss both treatment of the omphalocele as well as the potential for associated anomalies. Dr. Listernick: Lets start with the omphalocele itself. Dr. Barsness: The outcome is highly dependent on the size of the omphalocele and the state of the omphalocele sac. For a very small omphalocele, often called a

Omphalocele is a defect of the abdominal wall due to failure of fusion of the umbilical ring.
hernia of the cord, in which the contents come up into a sac which has the insertion of the umbilical vessels within it, associated intestinal complications are very low. Think of it as a large umbilical hernia. We close these defects at birth. We also close at birth larger omphaloceles that simply have intestinal contents in the sac, assuming the sac has not ruptured. Dr. Listernick: When does it get more complicated? Dr. Barsness: As more abdominal contents enter the sac, the more difcult it is to close and the incidence of complications rises dramatically. Once the liver enters the sac, it becomes extremely difcult to

Robert Listernick, MD, is Professor of Pediatrics at Feinberg School of Medicine, Northwestern University, and director of the Diagnostic and Consultation Service, Division of General Academic Pediatrics, The Ann and Robert H. Lurie Childrens Hospital of Chicago, Chicago, IL. doi: 10.3928/00904481-20120525-03

replace all the sacs contents back into a small peritoneal cavity. The retroperitoneal structures the duodenum, kidney and cecum may be the only things that remain in the abdominal cavity which was never forced to grow in utero because all the normal structures were in the omphalocele. In addition, if the liver is in the sac, its at an angle which kinks the inferior vena cava potentially causing ischemia to the liver or impeding venous return to the heart. Dr. Listernick: And the treatment for these large omphaloceles? Dr. Barsness: As long as the sac is intact, we typically paint the sac with dilute Betadine and use the sac as a temporary membrane to protect the abdominal viscera. We delay closure until the peritoneal cavity has enlarged enabling us to replace the viscera safely. Dr. Reynolds: Another important issue of which to make parents aware is the potential for associated pulmonary hypoplasia because the chest has not had a chance to expand in utero. An important reason to delay closure of giant omphaloceles is these infants lack of lung reserve. If they are taken to the operating room in the neonatal period, they may never be able to be safely removed from the ventilator. Dr. Listernick: What should be said to the parents about potential associated defects? Barbara Burton, MD, pediatric geneticist: Knowing that there are two

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Firm Rounds

anomalies and a 39-year-old mother, Id be very concerned about a chromosomal abnormality. Omphaloceles are particularly seen in infants who have trisomy 13 but may also be seen in those with trisomy 18. Beckwith-Wiedemann syndrome (BWS) is certainly another syndrome to consider. Even in babies who dont have a recognizable genetic syndrome, theres a signicantly increased risk of cardiac defects in babies who have an omphalocele. Dr. Listernick: What about counseling about the delivery itself? Can these infants be delivered vaginally? Daniel Robinson, MD, neonatologist: Children with some abdominal wall defects can be delivered vaginally. However, infants with a giant omphalocele are different. The obstetrician has to decide whether the baby can be safely delivered without rupturing the sac which could have fatal complications from liver hemorrhage. There are even some data suggesting that infants with small to moderate myelomeningoceles can be delivered safely vaginally as long as there arent signicant in utero hydrocephalus and macrocephaly. Dr. Listernick: This baby was born by Cesarean section due to failure to progress. Apgar scores were 2 at 1 minute, 8 at 5 minutes. An intact omphalocele was noted at birth and was wrapped in sterile gauze in a plastic bag. The family history was signicant for a male sibling who was delivered at 24-weeks gestation and passed away; we have no further information about that infant. On exam, he was a large infant whose weight was in the 90th percentile, length in the 97th percentile, and head circumference in the 10th percentile. He had a metopic capillary malformation and bilateral earlobe creases. The tongue was abnormally large. Lungs were clear. S1 and S2 were normal. There was a soft I/VI systolic murmur without diastolic component heard best at the left lower sternal

border. There was a 4-cm omphalocele with attached sac. There was no liver in the sac. The penis was normal with bilateral descended testes. The 5th toes were folded under the 4th toes. The neurologic exam was normal. Genetic testing revealed a 46 XY boy with a normal whole genome microarray. Dr. Barsness: We considered this a small omphalocele because the sac inserts on the abdominal wall, there is no liver within it and he has normal chest wall development and a good-sized abdominal cavity. Given its small size and the large abdominal domain, we were able to resect the sac, replace the contents into the peritoneal cavity and close the abdominal wall. Large defects not amenable to primary closure are left intact, kept moist and allowed to develop granulation tissue. They ultimately epithelialize. Dr. Listernick: What is the prognosis for infants with these isolated small omphaloceles? Dr. Barsness: Generally, its excellent. Babies who have gastroschisis have a high rate of associated intestinal atresias as well as subsequent necrotizing enterocolitis for unknown reasons. Dr. Listernick: Obviously theres more to this baby than the omphalocele. Dr. Burton: He clearly has a large birth weight, large tongue, forehead capillary malformation, and abnormal earlobe creases, all typical features of BWS. Other features to look for include hemihyperplasia and organomegaly. In addition, the neonatologist should be aware of the high incidence of hypoglycemia. Dr. Listernick: An irrelevant pearl for the day did you know that abnormal ear lobe creases in men are associated with a higher risk of coronary artery disease? File that fact away for use on a rainy day. So, what is the cause of BWS? Dr. Burton: Its complicated. In most patients its an epigenetic phenomenon in which there is no change in the genetic

Panelists
Robert Listernick, MD
Moderator, general academic pediatrician

Marletta Reynolds, MD
Pediatric surgeon

Kathy Barsness, MD
Pediatric surgeon

Barbara Burton, MD
Pediatric neurologist

Daniel Robinson, MD
Neonatologist

Don Zimmerman, MD
Pediatric endocrinologist

All panelists practice at The Ann and Robert H. Lurie Childrens Hospital of Chicago, IL, where this discussion, part of a weekly series, was recorded and transcribed for Pediatric Annals.

code but gene expression is altered due to genetic imprinting. The critical region is on chromosome 11, specically 11p15.5. The critical BWS region is normally silenced by methylation of the maternal chromosome and active on the paternal chromosome. BWS occurs in approximately 50% of cases due to loss of methylation (activation) of this region on the
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Firm Rounds

maternal chromosome. Twenty percent of cases are due to paternal uniparental disomy, inheritance of two copies of the paternal 11p15.5 region. Rarely, BWS may result from duplications or microdeletions that are detectable on whole genome microarray or from mutations of a specic gene which, if mutated, can impair methylation. These latter infants may have a family history of BWS. Dr. Listernick: How do you conrm the diagnosis of BWS? Dr. Burton: Once again, its complicated. We take a step-wise approach. Generally we start with whole genome microarray and methylation testing which detect approximately 60% of cases. Next, we may do testing for uniparental disomy which detects an additional 20% of cases. Dr. Listernick: Which babies in the nursery should we suspect have BWS and perform testing? Dr. Burton: Thats not clear. Its easy when you have the full spectrum of anomalies such as in this baby. For instance, some geneticists recommend BWS testing in all infants with seemingly isolated hemihyperplasia, macroglossia or omphaloceles. Dr. Listernick: Why do babies with BWS develop hypoglycemia? Don Zimmerman, MD, pediatric endocrinologist: Hypoglycemia occurs in approximately half of these children, usually lasting only days or several weeks. In about one tenth of those who are hypoglycemic, the hypoglycemia may persist for months or years. The mechanism is hyperinsulinism. It turns out that the 11p15.5 region contains a gene responsible for a potassium channel which regulates the release of insulin from the beta cells of the pancreas. Dr. Listernick: Why does the hypoglycemia improve over time? Dr. Zimmerman: Thats unknown.

Key Learning Points

1. O  mphalocele is a defect of the abdominal wall due to failure of fusion of the umbilical ring. Intestinal contents herniate through the defect covered by a sac, unless it has ruptured. Theres a high incidence of associated birth defects. 2. G  astroschisis results from rupture of a dysplastic abdominal wall or a vascular defect. There is neither a sac nor any associated extraintestinal birth defects. However, there is a high incidence of associated intestinal atresia and subsequent episodes of enterocolitis. 3. O  mphaloceles are associated with Trisomy 13 and Trisomy 18, as well as with BeckwithWiedemann syndrome (BWS). 4. C  hildren with BWS have an increased risk of Wilms tumor, hepatoblastoma, and adrenocortical carcinoma. Recommendations include serial abdominal ultrasonography every 3 months up to the age of 8 years and serum alpha-fetoprotein measurement on the same timetable up to the age of 4 years.

Dr. Listernick: Does anything need to be done about this childs macroglossia? Dr. Reynolds: This tongue is not particularly large in the grand scheme of macroglossia. Weve seen tongues so

The critical BWS region is normally silenced by methylation of the maternal chromosome and active on the paternal chromosome.
large that they are obstructing airways, necessitating tracheostomy and surgical reduction of tongue mass. Dr. Robinson: Although the tongue does not look enormous, it is causing the child some difculty eating and it produces signicant upper airway obstruction on sleep study. Were not out of the woods yet in so far as needing to deal with the macroglossia. The family is having a difcult time accepting the degree of macroglossia and are interested in a surgical solution. Dr. Reynolds: Over time, the tongue

will t into the oral cavity. It might be benecial to offer the family services through the Beckwith-Wiedemann Childrens Foundation which has its own website. They could contact other families with similar BWS children. Dr. Listernick: Wed be remiss if we didnt mention the increased risk of abdominal malignancies in BWS children. Dr. Burton: Theres an increased risk of Wilms tumor, hepatoblastoma and adrenocortical carcinoma, with an overall risk in the neighborhood of 8%. The risk is greater if the child has hemihyperplasia. Although the specics vary among institutions, most recommend serial abdominal ultrasonography every 3 months up to the age of 8 years and serum alpha-fetoprotein measurement on the same timetable up to the age of 4 years. I usually dont start getting the alpha-fetoprotein until 1 year of age. Dr. Reynolds: Having seen Wilms tumor in these patients present at a later age, Ive begun to continue the abdominal ultrasonography past age 8 years. Im not sure what my upper age limit will be to stop performing them, nor do I have any data to support this recommendation other than my anecdotal experience.

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