European Journal of Pediatrics

, Volume 167, Issue 1, pp 29–35

Pentalogy of Cantrell: two patients and a review to determine prognostic factors for optimal approach

  • Jeroen H. L. van Hoorn
  • Rob M. J. Moonen
  • Clément J. R. Huysentruyt
  • L. W. Ernest van Heurn
  • Jos P. M. Offermans
  • A. L. M. Twan Mulder
Open AccessReview

DOI: 10.1007/s00431-007-0578-9

Cite this article as:
van Hoorn, J.H.L., Moonen, R.M.J., Huysentruyt, C.J.R. et al. Eur J Pediatr (2008) 167: 29. doi:10.1007/s00431-007-0578-9

Abstract

Two patients with incomplete pentalogy of Cantrell are described. The first was a girl with a large omphalocele with evisceration of the heart, liver and intestines with an intact sternum. Echocardiography showed profound intracardiac defects. The girl died 33 h after birth. The second patient was a female fetus with ectopia cordis (EC) without intracardiac anomalies; a large omphalocele with evisceration of the heart, stomach, spleen and liver; a hypoplastic sternum and rib cage; and a scoliosis. The pregnancy was terminated. A review of patients described in the literature is presented with the intention of finding prognostic factors for an optimal approach to patients with the pentalogy of Cantrell. 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.

Keywords

Ectopia cordisPentalogy of CantrellAbdominal wall defect

Abbreviations

ASD

atrial septal defect

EC

ectopia cordis

MRI

magnetic resonance imaging

VSD

ventricular septal defect

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

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

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

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

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

Reference

Form

Cardial defect

Associated anomalies

Survival

Baker et al. 1984 [5]

CF

EC

Cloacal extrophy, genitourinary and spine anomalies

No

Soper et al. 1986 [38]

CF

EC, VSD

Occipital encephalocele 47,XX +18

No

Bick et al. 1988 [7]

CF

EC

Occipital encephalocele 47,XX +18, abnormally lobated small lungs, horseshoe kidney

No

Fox et al. 1988 [18]

CF

EC, single ventricle and atrium, bicuspid ventricular outflow valve, malpositioned right aortic arch

Bilateral clubfeet, spina bifida, hydrocephalus, abnormal ears, horseshoe kidneys: trisomy 18

No

Carmi and Boughman 1992 [11]

CF

EC, VSD, D-transposition of great vessels, pulmonary atresia, hepatic venous connection, common pulmonary vein

Large left cleft lip and palate

No

CF

EC, diverticulae of right and left ventricle

None

Yes

CF

EC, TOF

Bilateral cleft lip and palate, single-lobed left lung, intralobar pulmonary sequestration

No

CF

TOF, ASD

None

No

CF

TOF, pulmonary atresia

Right cleft lip, small ears, dysplastic toe nails

No

Martin et al. 1992 [27]

CF

EC, hypoplastic left ventricle and atrium, dilated right ventricle, pulmonary valve and artery

None

No

CF

ASD, VSD

None

No

Egan et al. 1993 [17]

IF

EC, hypoplastic left ventricle, single pulmonary vein

Sirenomelia

No

Abdallah et al. 1993 [1]

CF (?)

EC, TOF

None

Yes

Bogers et al. 1993 [9]

CF

EC, VSD, left and right ventricular diverticulum

None

Yes

Denath et al. 1994 [15]

IF

EC

Exencephaly, pulmonary hypoplasia

No

Siles et al. 1996 [36]

IF

 

None

Yes

IF

 

None

Yes

IF

VSD, double outlet right ventricle, bilateral superior venae cavae, pulmonary stenosis

None

Yes

Chen et al. 1996 [13]

CF (?)

 

None

Yes

Hornberger et al. 1996 [21]

?

 

None

No

?

 

None

No

Liang et al. 1997 [25]

IF

EC

None

No

Vazquez-Jimenez et al. 1998 [42]

IF

ASD, VSD, LVD, left superior vena cava without connection to the right system

Short, flat nose

Yes

Hsieh et al. 1998 [22]

CF

EC

Cystic hygroma

No

CF

EC

Cystic hygroma

No

Laloyaux et al. 1998 [24]

CF

VSD, ASD, tricuspid atresia, pulmonary stenosis

None

Yes

Song et al. 2000 [37]

IF

EC, single ventricle with double outlet, pulmonary atresia, tricuspid atresia

None

No

Morales et al. 2000 [29]

IF

EC, VSD, LVD, dextrocardia, double outlet right ventricle, right ventricle outflow tract obstruction, dextrocardia, VSD, double outlet right ventricle, pulmonary stenosis

Cleft palate, large encephalocele, hydrocephalus

Yes

IF

TOF

None

Yes

IF

 

None

Yes

Alayunt et al. 2001 [2]

CF (?)

VSD, LVD, ASD, TOF

None

Yes

Spencer et al. 2002 [39]

CF (conjoined twin)

EC, single anomalous multiventricular heart with ventricular septal defects, single common atria with three atrioventricular openings, anomalous systemic and pulmonary venous drainage; one twin: severe pulmonary stenosis; other twin: absent ductus ateriosus; common atria bilateral superior venae cavae; tricuspid, mitral and pulmonary valve aplasia; malrotation of the great vessels; aorticopulmonary communication

Thoracopagus twins

No

CF (conjoined twin)

ASD

Omphalopagus twins

No

Halbertsma et al. 2002 [20]

IF

LVD, ASD, VSD, anomalous venous pulmonary return

None

Yes

Nanda et al. 2003 [30]

CF

EC, VSD

Kyphoscoliosis, club foot

No

CF

EC, VSD

None

No

Onderoglu et al. 2003 [32]

CF

EC

Trisomy 21, pulmonary and extremity anomalies

No

Oka et al. 2003 [31]

CF

EC, PDA, LVD, tricuspid atresia, pulmonary stenosis, hypoplastic pulmonary arteries

None

Yes

Bittmann et al. 2004 [8]

CF

Small right ventricle, VSD, ASD

Gallbladder agenesis, polysplenia, segmentation defect of the lungs

No

Uygur et al. 2004 [41]

IF

EC

Left clubfoot, hypodactyly right hand, absent third finger of the right hand, absent left tibia and right radius

No

 

Patent foramen ovale

  
 

PDA

  

Aslan et al. 2004 [4]

IF

EC

Bilateral undescended testes, scoliosis, adherence between left upper limb and trunk, adrenohepatic fusion, anterior thoracic myeloschisis, multiple accessory spleens, renal agenesis

No

IF

EC

 

No

Correa-Rivas et al. 2004 [14]

CF

EC, ASD, PDA

Bilateral cleft lip and palate, bilateral pulmonary hypoplasia

No

Polat et al. 2005 [34]

CF

EC

Craniorachischisis, bilateral clubfoot

No

CF

EC

Craniorachischisis, bilateral clubfoot and clubhand

No

CF

EC

None

No

Marijon et al. 2006 [26]

IF

LVD, VSD

None

Yes

Bhat et al. 2006 [6]

IF

Dextrocardia, ASD

None

Yes

Araujo Junior et al. 2006 [3]

CF

EC, VSD

None

No

Knirsch et al. 2006 [23]

IF

Mesocardia, VSD, ASD, LVD

None

Yes

Chen et al. 2006 [12]

CF

EC, VSD

Scoliosis, hypoplasia of the right upper limb, ectrodactyly of the right hand and foot

No

Rashid et al. 2007 [35]

CF

EC

Encephalocele, club foot

No

Desselle et al. 2007 [16]

CF

EC, TOF

Non-rotation of the midgut, accessory spleen

Yes

Grethel et al. 2007 [19]

IF

Ventricular aneurysm

Morgagni hernia

Yes

McMahon et al. 2007 [28]

IF

EC, TOF, VSD, hypoplastic pulmonary valve

None

?

IF

EC, VSD

None

?

Our patients

IF

EC, TOF, ASD aberrant aortic valve

None

No

IF

EC

Low implant of left ear, hypoplastic right rib cage,scoliosis

No

CF Complete form, IF incomplete form, EC ectopia cordis, VSD ventricular septal defect, ASD atrial septal defect, TOF tetralogy of Fallot, LVD left ventricular diverticulum, PDA patent ductus arteriosus

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.

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jeroen H. L. van Hoorn
    • 1
  • Rob M. J. Moonen
    • 1
  • Clément J. R. Huysentruyt
    • 2
  • L. W. Ernest van Heurn
    • 3
  • Jos P. M. Offermans
    • 4
  • A. L. M. Twan Mulder
    • 1
  1. 1.Department of PediatricsUniversity Hospital MaastrichtMaastrichtThe Netherlands
  2. 2.Department of PathologyUniversity Hospital MaastrichtMaastrichtThe Netherlands
  3. 3.Department of SurgeryUniversity Hospital MaastrichtMaastrichtThe Netherlands
  4. 4.Department of Obstetrics and GynaecologyUniversity Hospital MaastrichtMaastrichtThe Netherlands