Seattle Children’s Hospital, University of Washington, Seattle, WA, USA
CLINICAL HISTORY:
A newborn premature male born to a 23-year-old G1P1 woman at 35 weeks and 6 days estimated gestational age was transferred from an outside facility due to presence of a small omphalocele and pulsatile mass in the sub-xiphoid region. He was prenatally diagnosed with dextrocardia, double outlet right ventricle (DORV) with normally related great vessels, subaortic ventricular septal defect (VSD), and bilateral choroid plexus cysts. Apgars were 5 and 8 at 1 and 5 minutes respectively, with a birth weight of 2.4 kg.
Following transfer, the infant had acceptable oxygen saturations for physiology in the 80’s on room air, with a 2/6 holosystolic murmur heard on physical exam. Abdominal ultrasound demonstrated a blind-ending pulsatile structure in the anterior abdominal wall that appeared to communicate with the heart (Figure 1 and Movie 1), possibly representing a ventricular diverticulum.
Figure 1 and Movie 1. Longitudinal grayscale (Figure 1) ultrasound image shows a tubular fluid filled structure (yellow arrows) extending inferiorly anterior to the liver through a defect in the anterior diaphragm. Color Doppler cine (Movie 1) demonstrates turbulent pulsatile flow in the structure communicating with the left ventricle. |
Transthoracic echocardiogram confirmed that the structure appeared to communicate with the left ventricle, and additionally demonstrated a large unrestrictive VSD, patent foramen ovale (PFO) and small patent ductus arteriosus, with normal right and left ventricle function. Cardiovascular magnetic resonance and chest MR angiography was performed at 4 days of life, for better assessment of congenital cardiac disease including left ventricular diverticulum, and to assess for Pentalogy of Cantrell.
CMR FINDINGS:
CMR (1.5T Avanto, Siemens) demonstrated a moderate subaortic VSD with predominantly left to right flow in the setting of dextrocardia (Movie 2, Figure 2), with slightly over-riding aorta but no significant pulmonary stenosis. Qp:Qs as measured from phase contrast flow measurements was 1.94. Right and left ventricular function was normal, with a relatively small left ventricular size of 27 ml/m2 (although normative values are lacking in the premature infant population). Additional findings included a tiny atrial level communication and a small patent ductus arteriosus.
  Movie 2 and Figure 2. Cine image and still frame from right heart long axis (RHLA) stack demonstrating dextrocardia with subaortic VSD (yellow arrow). |
Cine images demonstrated a tubular structure measuring 4 mm in diameter arising from the left ventricular apex, extending approximately 20 mm inferiorly below the xiphoid through the anterior diaphragm, consistent with Morgagni Hernia. This
contracted in synchronicity with the left ventricle, as expected of a left ventricular diverticulum (Movie 3).
 Movie 3. Multiple images from extended 2 chamber cine stack shows the left ventricular diverticulum (arrow) extending anterior to the liver below the diaphragm, with synchronous contraction with the left ventricle. |
Contrast enhanced time resolved MR angiography was performed with multipartition partial k space acquisition (Time-resolved angiography with Interleaved Stochastic Trajectories/TWIST) following administration of 0.2 mmol/kg Magnevist IV (Bayer, Leverkusen, Germany). The tubular, slightly tortuous diverticulum demonstrated contrast enhancement patterns matching that of the left ventricle, without evidence of internal thrombus (Movie 4). 3-dimensional volume rendering highlighted the tortuous and elongated configuration of the diverticulum (Figure 3).
  Movie 4 and Figure 3. Sagittal MIP images from time resolved contrast enhanced MRA (Movie 4) demonstrate enhancement within the left ventricular diverticulum (red arrow) simultaneously with the left ventricle. 3-D volume rendering (Figure 3) shows the tubular, tortuous configuration of the diverticulum (red arrow). |
Additional non-cardiac findings noted on the CMR included bifid inferior sternal ossification centers (Figure 4) and small supra-umbilical hernia/omphalocele. The left ventricular diverticulum did not enter or communicate with the omphalocele.
 Figure 4. Axial bright blood image with bifid sternal ossification centers (arrows). |
CONCLUSION:
The combined findings of ventricular septal defect, left ventricular diverticulum extending below the diaphragm via a Morgagni hernia, supra-umbilical omphalocele, and suggestion of sternal cleft are consistent with Pentalogy of Cantrell, albeit with an overall mild phenotype given the small size of the anterior abdominal defects. In the weeks following birth, the patient developed symptoms of pulmonary over-circulation, however responded well to diuretics. High calorie feeds were also required following slow initial weight gain. He was discharged home at 13 days of age.
Following time for adequate growth, combined surgical repair was performed at approximately 4 months of age, consisting of patch repair of the VSD, left ventricular diverticulum ligation and resection (Figure 5), diaphragmatic hernia repair, and omphalocele closure. Pathology confirmed well-formed bundled myocytes within the resected diverticulum, consistent with myocardial tissue and true diverticulum. His post-operative course was uneventful. He has done well throughout his childhood so far with persistently normal follow up echocardiograms.
 Figure 5. Intraoperative image with left ventricular diverticulum (arrow) exposed prior to ligation. |
PERSPECTIVE:
Cantrell and his colleagues defined Pentalogy of Cantrell in 1958 as a collection of five anterior midline thoracoabdominal defects. These are: 1) anterior diaphragmatic defect (Morgagni hernia), 2) midline supra-umbilical abdominal wall defect (omphalocele), 3) defect in the diaphragmatic pericardium, 4) intra-cardiac defect, and 5) defect of the lower sternum[1,2]. Toyama et al subsequently devised a classification system consisting of certain, probable, and incomplete Pentalogy. Patients possessing all five defects meet criteria for “certain” Pentalogy, while those in the “probable” category demonstrate four defects including a ventral wall defect and intra-cardiac defect. “Incomplete” Pentalogy consists of patients meeting multiple criteria but lacking the intra-cardiac or ventral wall defect[3].
The combination of anterior chest, diaphragm, and pericardium defects may lead to ectopic location of the cardiac structures, including full ectopia cordis or ectopic location of an associated ventricular diverticulum, but this is not required for diagnosis of the Pentalogy. Ectopia cordis is defined by partial or complete displacement of the heart outside of the thoracic cavity, and may result in an intra-abdominal location or complete external positioning of the heart anterior to the thoracic cavity through the associated sternal defect[3]. Sternal defects vary from complete bifid sternum/sternal cleft, short/absent distal sternum, or absent xiphoid process[4].
Intracardiac defects in Pentalogy of Cantrell vary widely. A recent meta-analysis by Mejias et al found the most common reported defects to be VSD and ASD, seen in 32.6% and 26.7% of patients respectively. Tetralogy of Fallot was seen in 12.0%, while a ventricular diverticulum was seen in 12.7%. Complete or partial ectopia cordis was reported in 45.8% of patients[5], although it is arguable that these cases may enter the literature as case reports at a greater frequency than those without.
Our case displays at least 4 defects, including Morgagni hernia, omphalocele, diaphragmatic pericardial defect containing the left ventricular diverticulum, and intra-cardiac defect. Bifid sternal ossification centers were also visible on cardiac MRI. Although bifid sternal ossification may be seen as a normal developmental variant, later failure of fusion of these ossification centers could lead to a sternal defect that would complete the 5 criteria of the Pentalogy.
Treatment and outcome depend heavily on the individual’s unique manifestations. Overall, survival rate in complete Pentalogy is as low as 37%[3]. However, the degree of congenital heart disease is extremely influential on survival, with complete ectopia cordis carrying a high mortality rate[3,5]. Likewise, treatment approach varies. Immediate management focuses on coverage of the mediastinum and achieving cardiopulmonary stability[5], both of which were already present at birth in our case.
Evaluation and treatment in this case was complicated due to the patient’s prematurity and small size at birth. Cardiac MRI was performed with sedation but without paralysis, intubation, or breath holds to minimize anesthetic risk. Multi-average cine image acquisition both compensates for respiratory motion as well as boosts signal in small neonates. Decreasing slice thickness and field-of-view as well as ensuring a relatively large matrix will improve spatial resolution. Segmented FLASH (fast low angle shot) cine imaging was used in this case due to turbulence artifact across the VSD, however in the absence of artifacts b-SSFP (balanced steady-state free precession) cine imaging typically provides superior image quality and endomyocardial differentiation, even in neonates.
Early surgical repair of ventricular diverticula is recommended given risk of thrombosis, rupture, and fatal tachyarrhythmias[6]. However, this must be weighed against the inherent risk of immediate operative repair in a 2.4 kg infant who is otherwise stable. Although many of the findings leading to diagnosis of Pentalogy of Cantrell were identifiable via physical examination and echocardiogram alone, cardiac MRI provided valuable anatomic and physiologic detail for pre-surgical planning and risk stratification, leading to the decision to allow a few months growth prior to single stage repair of the diverticulum, intra-cardiac defects, and omphalocele.
Click here to view the Cardiac MRI images for the case on CloudCMR
REFERENCES:
- Chandran S, Ari D. Pentalogy of cantrell: An extremely rare congenital anomaly. J Clin Neonatol. 2013;2:95.
- Morales JM, Patel SG, Duff JA, Villareal RL, Simpson JW. Ectopia cordis and other midline defects. Ann Thorac Surg. 2000;70:111–4.
- Williams AP, Marayati R, Beierle EA. Pentalogy of Cantrell. Semin Pediatr Surg. 2019;28:106–10.
- Grigore M, Micu R, Matasariu R, Duma O, Chicea AL, Chicea R. Cantrell syndrome in the first trimester of pregnancy: imagistic findings and literature review. Med Ultrason. 2020;22:189.
- Mejías EM, Carrión E, Sparman A, Juliana A. What is pentalogy of Cantrell? Cardiol Young. 2024;1–3.
- Vazquez-Jimenez JF, Muehler EG, Daebritz S, Keutel J, Nishigaki K, Huegel W, et al. Cantrell’s Syndrome: A Challenge to the Surgeon. Ann Thorac Surg. 1998;65:1178–85.
Case prepared by:
Erin Romberg, MD
Seattle Children’s Hospital
University of Washington