Synonyms: Thoraco-abdominal ectopia cordis; Cantrell-Heller-Ravitch syndrome; pentalogy syndrome; peritoneopericardial diaphragmatic hernia.

Definition: The complete syndrome is characterized by two major defects: ectopia cordis and an abdominal wall defect (most commonly an omphalocele, but gastroschisis can also be present). The other three defects of the pentalogy are disruption of all the interposing structures: the distal sternum, anterior diaphragm and diaphragmatic pericardium. Incomplete expressions have also been reported.

Prevalence: Very rare. Less than 90 cases have been reported in the literature, and even fewer have had the complete syndrome confirmed.

Etiology: Unknown. Sometimes associated with chromosomal abnormalities.

Pathogenesis: Postulated developmental failure of a segment of the mesoderm between 14 and 18 days after conception.

Associated anomalies: Intracardiac anomalies (i.e., tetralogy of Fallot) are the rule. Others include cranial and facial anomalies, chromosomal abnormalities, clubfeet, malrotation of the colon, hydrocephalus, and anencephaly¹.

Differential diagnosis: Isolated thoracic cardiac ectopy, ectopia cordis associated with amniotic band syndrome, body stalk abnormality, isolated omphalocele.

Prognosis: Survival is variable but uncommon and may depend on the size of the abdominal wall defect, extent of the cardiac defect, and presence of associated anomalies.

Recurrence risk: Unknown. No recurrence has been recorded. One set of monozygotic twins concordant for the syndrome has been reported².

MESH Heart-Defects,-Congenital-complications; Sternum-abnormalities; Thorax abnormalities; Diaphragm-abnormalities; Hernia,-Ventral BDE 3121 POS 3248 ICD9 754.89 CDC 754.820

Address correspondence to Sabrina D. Craigo, MD, Department of Maternal- Fetal Medicine, St.Margaret"s Hospital for Women, 90 Cushing Avenue, Boston, MA 02125-2099, Ph 617-436-8600, Fax 617-288-6828

Introduction

Thoraco-abdominal ectopia cordis, or pentalogy of Cantrell, is a rare congenital syndrome of abdominal wall defect (usually omphalocele), lower sternal defect, diaphragmatic pericardial defect, anterior diaphragmatic defect, and intracardiac abnormalities. First described by Cantrell in 1958, the syndrome occurs sporadically, with variable degrees of expression^1,3.

The proposed pathogenesis involves a defect in embryogenesis between 14 and 18 days after conception, when the splanchnic and somatic mesoderm are dividing. Many associated anomalies have been reported in fetuses with Pentalogy of Cantrell, including cranial and facial anomalies, clubfeet, malrotation of the colon, hydrocephalus, and anencephaly. Chromosomal abnormalities have also been associated with the syndrome^1,4.

Prenatal diagnosis by ultrasonography is possible, depending on the size and extent of the defects. We report a case of pentalogy of Cantrell diagnosed at birth in an infant with nonimmune hydrops. A second trimester ultrasound study appeared normal, but a very small omphalocele was diagnosed sonographically in the third trimester.

Case report

The patient was a 28-year-old G₂P₀, with dates confirmed by a 12-week sonogram. She presented for a level II ultrasound exam at 19 weeks gestation secondary to an elevated maternal serum alpha-fetoprotein of 2.8 multiples of the mean. Ultrasound examination revealed no abnormalities (fig. 1).

Fig. 1: 19 weeks examination. Section at the level of the heart (left) and cord insertion (right). No clear evidence of anomaly is detected.

She declined amniocentesis. Repeat sonogram at 22 and 29 weeks again showed no abnormalities, but at 29 weeks gestation umbilical artery Doppler S/D ratios were elevated at 5.1.

She returned for ultrasound examination at 31 weeks gestation, and fetal hydrops was discovered, with pleural effusion, pericardial effusion, and ascites. A small ventral wall defect was identified at the cord insertion, with no herniation evident (fig. 2).

Fig. 2: At 31 weeks, the heart is seen at the edge of the chest, and bilateral pleural effusions are noted (left). Ascites and a small abdominal wall defect without evidence of herniation are seen at the level of the cord insertion (right).

Doppler studies showed absent end-diastolic flow. Mild polyhydramnios was noted. Amniocentesis was performed for chromosomal analysis, which later returned as normal 46 XX.

Her pregnancy had been uncomplicated except for well-controlled gestational A₁ diabetes mellitus. Pertinent laboratory tests included maternal blood type B negative, antibody titer positive for cold agglutinins, RPR nonreactive, rubella nonimmune.

The patient was hospitalized for daily fetal testing. All non-stress tests were reactive. Moderate hydrops persisted. Four days after admission the patient had spontaneous rupture of membranes with clear fluid. Labor ensued and she underwent a primary low transverse cesarean section with delivery of a viable female infant weighing 3060g. The infant was grossly edematous with an abdominal wall defect extending from the cord insertion superiorly over the apex of the heart (fig. 3).

Fig. 3: An abdominal wall defect extends from the cord insertion superiorly over the apex of the heart.

The umbilical cord was short and the cord pH was 7.32. The infant was Rh Du negative. Her initial hematocrit was 42.8, WBC 3.54, and platelet count 206,000. The infant"s initial heart rate was below 100. She was intubated immediately and given chest compressions and epinephrine. She was placed on broad-spectrum antibiotics and was given one dose of surfactant. Bilateral thoracenteses were performed and a chest tube was placed. Echocardiography demonstrated a ventricular septal defect, patent ductus arteriosus, patent foramen ovale, and good cardiac function. The infant was taken to surgery, where pericardial and anterior diaphragmatic defects were confirmed.

The omphalocele was repaired and the pericardial and sternal defects were closed. Estimated blood loss was 3 cc. The infant was unstable, requiring volume and pressor agents. In the neonatal intensive care unit she developed bradycardia and hypotension shortly after surgery. Resuscitation efforts were un­success­ful. The chest was opened to rule out cardiac tamponade, and no blood was found surrounding the heart. She expired 20 hours after delivery.

The autopsy confirmed the intracardiac defect (VSD) (fig. 4) and noted nonfixation of the cecum. Renal, hepatic, and pulmonary congestion were noted.

Fig. 4: The probe is placed in the ventricular septal defect.

The maternal serological tests to toxoplasmosis, rubella, and cytomegalovirus were negative. Parvovirus IgG was positive, and IgM was indeterminate on first testing, trace positive on second. Placental pathology showed a 640g placenta consistent with 31 weeks, with widespread moderate villous edema.

Discussion

Embryogenesis

The sternum, abdominal wall, pericardium, and part of the diaphragm arise from somatic mesoderm, while the myocardium arises from splanchnic mesoderm. An event occurring prior to differentiation of the mesoderm into these two layers could produce defects in all of the involved structures, as seen in pentalogy of Cantrell. Although a specific etiology is unknown, the timing of the event or insult would be between 14 and 18 days after conception. The proposed embryogenesis postulates a failure of the lateral mesodermal folds to migrate to the midline (fig. 5), causing the sternal and abdominal defects, and failure of the septum transversum to develop, causing defects in the anterior diaphragm and pericardium^3,5.

Fig. 5: During the third week of development, newly formed mesodermal cells migrate into the area of the germ disk, between the ectoderm and endoderm.

Ultrasound diagnosis

Diagnosis of the complete syndrome requires the five criteria described by Cantrell, but incomplete variant forms exhibiting three or four of the features have been described¹. The sternal defect can range from absence of the xiphoid to cleaving, shortening, or absence of the entire sternum. The abdominal defect can range from a wide rectus muscle diastasis to a large omphalocele. The most common intracardiac defects are atrial septal defect, ventricular septal defect, and tetra­logy of Fallot⁶.

The syndrome has been diagnosed prenatally^5,7,8, but as the defects range from subtle to severe, the ability to make the ultrasound diagnosis varies. Even at birth, the full extent of the syndrome may not be apparent, as the sternal defect may be minor and therefore without true ectopia cordis. In the case presented, a small open sternal defect was contiguous with the upper portion of the small omphalocele, but the heart and bowel did not protrude through these defects. In the prenatally detected cases which have been reported, ectopia cordis was present.

Differential diagnosis

Differential diagnosis includes isolated ectopia cordis, isolated abdominal wall defect, amniotic band syndrome, and body stalk anomaly. The syndrome should be considered with any diagnosis of omphalocele or ectopia cordis.

Prognosis

In a review of the literature in 1972, Toyama reported a survival rate of 20%. This observation included cases with mild defects and incomplete expressions of the syndrome, and all cases were diagnosed after delivery¹. In Ghidini"s 1988 report of 17 prenatally diagnosed cases, 6 patients opted for termination, 4 infants were stillborn, 4 infants died in the first four days after delivery, and the remaining 3 died at one, four, and four months. This gave a survival rate of 0%⁸. These cases were prenatally diagnosed, so the extent of anomalies could have been more severe than those cases detected at birth. Three of the five patients Cantrell reported in 1958 survived, but none of the five had true ectopia cordis³. Overall the prognosis appears dismal, but may be related to the extent of the ventral wall, sternal, and cardiac defects.

Associated anomalies

If a diagnosis is made by ultrasound, chromosomal analysis is recommended. Associations with trisomy 18, trisomy 13, and Turner syndrome have been reported^4,6. Careful imaging should be performed to rule out associated anomalies. Fetal echocardiography is indicated to evaluate the extent of any intracardiac abnormalities⁸.

Management

In view of the poor prognosis, termination of pregnancy can be considered if ultrasound diagnosis is made before viability. In patients choosing to continue the pregnancy, there is no data indicating improved or changed outcome with cesarean delivery⁸.

After delivery, repair of the omphalocele should not be delayed. Repair of the sternal, diaphragmatic, and pericardial defects can be attempted at the same time. Surgical correction is often difficult secondary to hypoplasia of the thoracic cage and inability to enclose the ectopic heart. Some affected infants have respiratory insufficiency secondary to pulmonary hypoplasia. Recognition and treatment of any intracardiac anomaly is important, as congenital heart disease is a source of major morbidity in infants surviving the neonatal period⁶.

References

1. Toyama WM: Combined congenital defects of the anterior abdominal wall, sternum, diaphragm, pericardium, and heart: a   case report and review of the syndrome. Pediatrics 50:778-792, 1972.

2. Baker ME, Rosenberg ER, Trofatter KF et al: The in utero findings in twin pentalogy of Cantrell. J Ultrasound Med 3:525-527, 1984.

3. Cantrell JR, Haller JA, Ravitch MM: A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium, and heart. Surg Gynecol Obstet 107:602-14, 1958.

4. Fox JE, Gloster ES, Mirchandani R: Trisomy 18 with Cantrell Pentalogy in a Stillborn Infant. American Journal of Medical Genetics 31:391-394,1988.

5. Haynor DR, Shuman WP, Brewer DK: Imaging of fetal ectopia cordis: roles of sonography and computed tomography. J Ultrasound Med 3:25-27,1984.

6. Bryke CR, Breg WR: Pentalogy of Cantrell. from Buyse,   M.L., Birth Defects Encyclopedia. Blackwell Scientific Publications 1375-76,1990.

7. Abu-Yousef MM, Wray AB, Williamson RA, Bonsib SM: Antenatal Ultrasound Diagnosis for Variant of Pentalogy of Cantrell. J Ultrasound Med 6:535-538, 1987.

8. Ghidini A, Sirtori M, Romero R, Hobbins JC: Prenatal Diagnosis of Pentalogy of Cantrell. J Ultrasound Med 7:567-572,1988.