Introduction

The pentalogy of Cantrell was first described in 1958 [10]. The hallmark of this syndrome is an omphalocele associated with ectopia cordis (EC). The full spectrum consists of five anomalies: a deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, various congenital intracardiac abnormalities, and a defect of the lower sternum. Only a few patients with the full spectrum of the pentalogy have been described. We present two patients with incomplete pentalogy of Cantrell. We reviewed the literature to find prognostic factors that may help to assess the best multidisciplinary approach in prenatal counselling and in postnatal therapy in patients with the pentalogy of Cantrell.

Case reports

Patient 1

A prenatal ultrasound in a 26-year-old G1P0 showed a fetus with bilateral hydrothorax, EC with a ventricular septal defect (VSD), and a large omphalocele with evisceration of the heart and the liver. The diagnosis of pentalogy of Cantrell and the prognosis were discussed with the parents. The prenatal medical team together with the parents decided to continue the pregnancy. At 39 weeks and 1 day of gestational age, a girl was delivered by primary cesarean section with Apgar scores of 6 and 8 at 5 and 10 min, respectively. Birth weight was 2,310 g (<p 2,3). There was a large omphalocele with evisceration of the heart, liver and intestines (Fig. 1); on palpation the sternum was intact. Echocardiography showed tetralogy of Fallot with a VSD, pulmonary valve stenosis and an aberrant aortic valve, a large atrial septal defect (ASD), and signs of pulmonary hypertension. The girl was intubated 30 min after birth. Due to progressive respiratory distress, conventional mechanical ventilation was switched to high-frequency oscillation. Endotracheal instillation of surfactant and evacuation of 45 ml pleural fluid were performed without any clinical improvement. Treatment with inhaled nitric oxide, inotropic support of the heart and systemic blood pressure, and prostaglandin E1 (Prostin VR Paediatric) to preserve the ductus-dependent circulation were started. Despite this treatment, the child remained hypotensive with oxygen saturation levels between 50 and 60%. The girl died 33 h after birth. The parents refused autopsy.

Fig. 1
figure 1

Patient 1 with a large omphalocele with evisceration of the heart (arrow), liver and intestines

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Patient 2

A prenatal ultrasound in a 19-year-old G1P0 showed a fetus with EC with a VSD; a large omphalocele with evisceration of the heart, stomach, spleen, and liver; and a scoliosis. After discussing the diagnosis of pentalogy of Cantrell and related prognosis with the parents, the pregnancy was terminated at 23 weeks and 4 days of gestational age.

Post-mortem examination showed a female fetus presented with a large omphalocele with evisceration of the liver, spleen, and a major part of the gastro-intestinal tract (Fig. 2). The heart was situated directly under the skin, not protected by the ribs or the hypoplastic sternum. The anterior diaphragm was absent and a peritoneal-pericardial connection was found. Furthermore the fetus was characterized by a low implant of the left ear, a severe scoliosis, and a hypoplastic right ribcage with both lungs positioned in the left ribcage. Because of its small size, the heart was examined under the dissecting microscope, but a VSD or another intracardial defect could not be found.

Fig. 2
figure 2

Post-mortem examination of patient 2 showed a large omphalocele with evisceration of the liver, spleen and a major part of the gastro-intestinal tract. The arrow indicates the heart covered with skin

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Histopathological examination showed dysmaturity of the lungs due to the intrathoracal malpositioning. The other organs showed no major abnormalities on microscopy.

Discussion

The pentalogy of Cantrell is a rare syndrome with an estimated incidence of 5.5 per 1 million live births [11]. It is described as a deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, various congenital intracardiac abnormalities, and a defect of the lower sternum. The pathogenesis of pentalogy of Cantrell has not been fully elucidated. Cantrell et al. [10] suggested an embryologic developmental failure of a segment of the lateral mesoderm around gestational age 14–18 days. Consequently, the transverse septum of the diaphragm does not develop, and the paired mesodermal folds of the upper abdomen do not migrate ventromedially. Organs may eviscerate through the resulting sternal and abdominal wall defects. EC itself is characterized by complete or partial displacement of the heart outside the body. Cervical, cervicothoracic, thoracic, and thoracoabdominal types of EC have been described [29].

Intracardiac anomalies are described in the pentalogy of Cantrell including VSD (100%), ASD (53%), tetralogy of Fallot (20%), and ventricular diverticulum (20%) [10]. Various other associated anomalies have been reported and include craniofacial and central nervous system anomalies such as cleft lip and/or palate, encephalocele, hydrocephalus, and craniorachischisis [14, 29, 34]; limb defects such as clubfoot, absence of tibia or radius, and hypodactyly [33, 41]; and abdominal organ defects such as galbladder agenesis and polysplenia [8]. Often the spectrum of the original pentalogy of Cantrell is not complete. Toyama [40] suggested the following classification of the pentalogy of Cantrell: class 1, definite diagnosis, with all five defects present; class 2, probable diagnosis, with four defects present, including intracardiac and ventral wall abnormalities; and class 3, incomplete expression, with various combinations of defects present, including a sternal abnormality. In our first patient, the sternum was intact, and in addition to the large omphalocele, there were diaphragmatic and intracardiac defects. The second patient had a sternal defect with associated anomalies such as a low implant of the left ear, a hypoplastic right rib cage and a scoliosis. There were no intracardiac anomalies. We considered both patients to be incomplete forms of the pentalogy of Cantrell.

With prenatal ultrasonography, the pentalogy of Cantrell usually can be diagnosed in the first trimester of pregnancy [25]. In a fetus with omphalocele, pentalogy of Cantrell should be ruled out. If pericardial effusion can be seen, associated anterior diaphragmatic hernia and diaphragmatic pericardial defects may be suspected, and specific and detailed search for the features of the pentalogy of Cantrell, as described above, should be done [36]. Use of prenatal magnetic resonance imaging (MRI) may enhance the visualization of the fetal anomalies [28].

After birth, echocardiography is essential for diagnosis of associated cardiac anomalies. Other features of the pentalogy of Cantrell and known associated anomalies can be diagnosed by conventional radiography or sonography. Nevertheless, small defects of the diaphragm and pericardium can be extremely difficult to diagnose accurately. In these patients and in cases of possible surgical intervention, MRI might be useful [31, 37].

The treatment of the pentalogy of Cantrell consists of corrective or palliative cardiovascular surgery, correction of ventral hernia and diaphragmatic defects and correction of associated anomalies. The best treatment strategy depends on the size of the abdominal wall defect, the associated heart anomalies, and the type of EC.

To find prognostic factors that might help to determine the best strategy in patients with the pentalogy of Cantrell we performed a literature search of patients with pentalogy of Cantrell described in the English literature over the last 20 years. The results are shown in Table 1. An overview of patients described earlier was made by Toyama et al. in 1972 [40]. Our search on Pubmed using the search terms “pentalogy of Cantrell” and “Cantrell’s syndrome” yielded 58 patients with pentalogy of Cantrell between 1987 and April 2007. Thirty-three patients were described as complete and 23 patients as incomplete. Two patients were not clearly defined as complete or incomplete. Fourteen patients had EC without intracardiac anomalies, 16 patients had intracardiac defects without EC, and 23 patients had both. Other associated anomalies were described in 29 patients. Thirty-seven of 58 patients, including patients in whom pregnancy was terminated, died within days after birth. This mortality from the reported literature may be higher because successful treatment of these patients is considered rare, and therefore these patients will be reported relatively more often. In this selected group, the mortality was higher in the patients with associated anomalies and if the complete form was present. The surviving patients with EC were those with associated intracardiac anomalies. This suggests that intracardiac defects may favor the prognosis. However, a selection bias was present due to the small number of patients.

Table 1 Review of patients with pentalogy of Cantrell (complete and incomplete form) with cardial defects, associated anomalies, and outcome
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In conclusion, the prognosis seems to be poorer in patients with the complete form of pentalogy of Cantrell, EC, and patients with associated anomalies. Intracardial defects do not seem to be a prognostic factor. When the diagnosis pentalogy of Cantrell is suspected, a multidisciplinary approach is essential. A prenatal medical team consisting of a gynecologist, a neonatologist, a pediatric cardiologist, a geneticist, and a pediatric surgeon should use their expertise in choosing the best approach to this severe disorder.