Pentalogy or Hexalogy of Cantrell?

Pentalogy of Cantrell (PC) is a rare congenital defect associated with five midline anomalies. The type of cardiac malformation and the size of the abdominal wall defect is often responsible for the high mortality. Of interest, the embryonic period in which PC develops is similar to that of the umbilical cord's (UC) formation. The aim of the following study was to investigate the relationship between UC anomalies and PC. Charts of four cases with PC from 2002–08 were retrospectively reviewed for associated UC anomalies. UC anomalies were defined as single umbilical artery (SUA), short cord (during 1st trimester less than CRL or less than 30cm at term) or atypical UC coiling pattern. We identified four cases: 3 singletons and one monochorionic diamniotic twin pregnancy with TRAP sequence. All cases showed a normal karyotype. All but one demonstrated the classical pulsatile omphalocele with ectopia cordis and all others anomalies of PC. One case was characterized by a major cranial omphalocele without ectopia cordis and no UC anomaly. This fetus was delivered by Cesarean at term and successfully operated on d1. In all other cases the parents requested ToP. Among the three cases with ectopia cordis, two had a short UC with SUA and one a short three-vessel cord; all these three UC were markedly uncoiled. Our data suggest a strong association between Cantrell and the development of the UC, in particular in cases with ectopia cordis. One might speculate that hemodynamic alterations of the feto-placental blood flow because of the cardiac malformation or structural changes at the umbilical ring (omphalocele) influence the development of the UC. More observations are needed to decide if Cantrell is a “hexalogy” instead of pentalogy.

Cantrell Syndrome (Thoracoabdominal Ectopia Cordis; Anomalous Umbilical Cord; Diaphragmatic, Pericardial and Intracardiac Defects) in the Pig (Sus scrofa domesticus)

Cantrell syndrome, a rare congenital disorder, is characterized by a unique collection of defects on the midline abdominal wall, the lower sternum, the anterior diaphragm, and the diaphragmatic pericardium in addition to some form of intracardiac defect. So far, most of the reports on fetuses with Cantrell syndrome worldwide are either case reports or literature reviews, and few comprehensive studies on fetuses with Cantrell syndrome have been reported, especially in domestic literature. This study aims to provide a detailed analysis of 15 cases of Cantrell syndrome fetuses, focusing on their prenatal ultrasound manifestations and postnatal examination outcomes. A retrospective analysis was conducted with 15 cases of fetuses diagnosed with Cantrell syndrome via prenatal ultrasound examinations between March 2018 and July 2023. Ultrasound examinations were performed in accordance with the Guidelines for Obstetric Ultrasound in China, including first-trimester fetal ultrasound scan and routine second-trimester fetal ultrasound scan. Gestational age was evaluated and nuchal translucency (NT) was measured during first-trimester fetal ultrasound scan at 11 to 13+6 weeks. The diagnostic criterion for NT thickening was NT≥3.0 mm and the screening of severe fetal structural malformations was performed, including the screening of the head, the neck, the thorax, the abdominal content, the abdominal wall, the limbs and other structures. During routine second-trimester fetal ultrasound scan, the fetal biometry was assessed and an anatomy survey was performed. Post-induction and postnatal outcomes of fetuses diagnosed with Cantrell syndrome by prenatal ultrasound were followed up by postnatal observation, inquiries with the electronic medical record system, or telephone follow-up. The prenatal ultrasound imaging manifestations and features of the fetuses with Cantrell syndrome, as well as their post-induction or postnatal examination results were comprehensively summarized and analyzed. The study involved pregnant women of the average age of 30.1±3.5 years, with ultrasound diagnoses made between 11 to 26 weeks of gestation (mean: 13.4±4.0 weeks). Among the 15 cases, there were 10 singleton pregnancies and 5 cases of one twin in a pair of twins. These twins comprised 3 monochorionic diamniotic twins and 2 dichorionic diamniotic twins, with Cantrell syndrome present in one of the twins in all 5 cases. Thirteen cases were diagnosed by fetal ultrasound scan conducted in the first trimester, with 10 being singleton pregnancies and 3 being twin pregnancies (1 monochorionic diamniotic twins and 2 dichorionic diamniotic twins). One case was missed in the first-trimester ultrasound scan, resulting in a missed diagnosis rate of 7.1%. Two cases were diagnosed in second-trimester fetal ultrasound scan, both involving monochorionic diamniotic twins. One case was a referral from another hospital at 19 weeks, while the other was initially not diagnosed for Cantrell syndrome and was diagnosed at 26 weeks. Prenatal ultrasound examinations revealed a consistent pattern of abnormalities across all 15 fetuses, including manifestations of ectopic cordis combined with abdominal protrusion mass. Specifically, 4 cases were diagnosed with omphalocele, 4 with gastroschisis, and the remaining 7 had uncertain coverage of the membrane on the surface of the abdominal protrusion mass. Six fetuses had complete ectopic cordis, while nine had partial ectopic cordis. Fetal echocardiography was performed in 5 cases, revealing intracardiac malformations in 4 cases (80%). Notably, 2 cases were diagnosed in the second trimester, including one with right ventricular hypoplasia accompanied by interventricular septal defect and another with double outlet right ventricle accompanied by interventricular septal defect. Additionally, 2 cases were diagnosed in the first trimester, one with single atrium and single ventricle, and the other with complete transposition of the great arteries. Of the 15 cases of fetuses with Cantrell syndrome, 13 (86.7%) exhibited concomitant malformations in other systems. These included 7 cases of spinal malformations, 4 limb abnormalities, 3 umbilical cord abnormalities, 2 central nervous system malformations, 1 facial malformation, and 2 fetal hydrops. Spinal malformations were the most prevalent concomitant malformation, accounting for 46.7% of all cases. Among the 14 fetuses undergoing NT examination, 7 (50%) had increased NT, and 5 of them had cystic hygroma. All 10 singleton pregnancies underwent induced abortion, and the appearance of the induced fetuses was consistent with the prenatal ultrasound manifestations. In the twin pregnancies, 2 cases experienced intrauterine fetal death, while 2 underwent selective reduction. Notably, 3 of these cases exhibited postnatal appearances consistent with prenatal ultrasound manifestation, while 1 case showed an indistinct appearance after selective reduction during delivery. One case was lost to follow-up. Genetic testing was conducted for 4 induced fetuses, none of which yielded any relevant pathogenic or potentially pathogenic variants. In conclusion, Cantrell syndrome manifests prenatally with ectopic cordis combined with abdominal protrusion mass, often accompanied by intracardiac malformations and other concomitant malformations. While most cases can be diagnosed in the first trimester, there remains the possibility of missed diagnoses, which underscores the importance of close follow-up in the second trimester.

Pentalogy of Cantrell.

Medical imaging plays a significant role in the detection of foetal anomalies, such as the Pentalogy of Cantrell (POC). POC is a congenital anomaly involving five or fewer body malformations: ectopia cordis (EC), tetralogy of fallot (TOF), sternal defects, diaphragmatic defects, and abdominal wall defects. The commonly used imaging modality in the detection of POC during pregnancy is ultrasound because it uses non-ionising radiation, is cheap, and is available in most medical facilities. We report a rare case of POC from a medical imaging standpoint in Zambia. Two obstetric ultrasound scans were performed in the 3rd trimester. The initial scan revealed, among other things, unappreciated abdominal contents, while the second scan revealed a foetal heart sited partially external to the thoracic cavity, with external herniation of the liver and bowels. Our case was classified as incomplete POC because not all five main malformations were present. This case report highlights the importance of having well-organised obstetric ultrasound imaging services both in urban and rural parts of the country to improve antenatal care.
 ABBREVIATIONS
 EC - Ectopia Cordis
 
 IUFD - Intrauterine Foetal Death
 POC - Pentalogy of Cantrell
 TOF - Tetralogy of Fallot
 VSD - Ventricular Septal Defect

Twin pregnancy in which both fetuses have Cantrell's pentalogy: A case report and literature review

Introduction Umbilical cord (UC) abnormalities and their clinical relations in 434 newborns were analyzed. We had previously reported on clinical associations of long and short UCs with any kind of malformation. This study focuses on other UC features (insertion, vessels, entanglements, coiling, and knots) and their associations with clinical characteristics and neonatal prognosis. Methods An observational analytic study was performed on placentas from consecutive deliveries. Ordered logistic regression with bivariate and multivariate analysis was performed to evaluate the relationship between variables of interest concerning UC abnormalities. Results A total of 434 placentas made up the study. UC abnormalities were abnormal insertion, 82 (18.86%); coiling (hypo and hypercoiled), 177 (40.78%); single umbilical artery (SUA), 4 (0.92%); entanglements, 8 (1.84%); true knots, 3 (0.69%); webs in UC base, 9 (2.07%); and right twist, 68 (15.67%). After analyzing maternal and fetal complications during pregnancy, multivariate analysis confirmed the recognized association between malformations and SUA and male gender; further confirmation was also made between hypertensive disorders of pregnancy and true knots. Discussion UC abnormalities associated with undesirable outcomes are varied and should be recognized and described. Clinical factors associated with anatomical UC abnormalities are not completely understood and justify forthcoming studies.

Complex management of ectopia cordis complicated by pentalogy of cantrell: Report of two cases and review of current evidence.

Pentalogy of Cantrell (PC) is a rare anomaly marked by the coexistence of omphalocele and ectopia cordis. Pentalogy of Cantrell comprises of the following five characteristics: midline, upper abdominal wall disorder (e.g. omphalocele, gastroschisis); defect of lower sternum (i.e. cleft sternum or absent sternum); anterior diaphragmatic defect (i.e. hypoplastic diaphragm, anterior diaphragmatic hernia); pericardial abnormality (e.g. ectopia cordis); congenital abnormalities of the heart (e.g. tetralogy of Fallot, ventricular septal defect, atrial septal defect). Toyama classified this syndrome into: class I – the occurrence of all 5 defects; class – II the occurrence of 4 defects with intracardiac and ventral abdominal wall abnormalities definitely present; class III – an incomplete expression of the disorders showing various combinations of defects, although sternal anomalies are definitely present. The incidence is estimated 5.5 – 7.9 per 1 million live births with male predominance. PC can be diagnosed since antenatal through ultrasonography examination. Unfortunately, the mortality rate is quite high with minimal survival rate even with surgical reconstruction. We present a case of one-day old infant whom was referred from West Nusa Tenggara with suspicion of PC syndrome and neonatal pneumonia. The baby was born through cesarean section with mild asphyxia, birth weight was 3000 gram and body length was 48 cm. There was no family and pregnancy risk factor. The multidisciplinary team consist of neonatologist, pediatric cardiologist and pediatric surgeon was teamed up to handle this case. There were some abnormalities in complete blood counts such as decreasing number of lymphocyte and neutrophil percentage and also increasing basophil percentage. Chest and abdominal X-ray showed a suspicion of pneumonia but this didn’t align with our physical examination. Echocardiography showed the infant had congenital heart defects such as Taussig Bing anomaly, single atrium, mild valvular pulmonary stenosis, mild tricuspid regurgitation and mesocardia. Genetic testing and further radiologic examination other than plain X-ray were not done in this case. There was no further intervention for this patient other than regular echocardiography and antibiotic topical treatment.

SummaryBackgroundPentalogy of Cantrell (POC) is an extremely rare and complex congenital anomaly. Ultrasound is a valuable, safe, nonionizing, cost effective, widely available, and easily reproducible imaging tool and is indispensible in the diagnosis of POC. Despite the rarity of POC, it is imperative for a radiologist to be aware of its wide spectrum of presentation on ultrasound in first trimester of gestation. Most reported cases in literature till now have been sporadic. In this paper, we aimed to report for the first time in literature, a recurrent case of POC detected in the first trimester in a mother whose previous pregnancy also was terminated in the second trimester medically due to the ultrasound diagnosis of POC. We also discuss the role of ultrasound and other imaging modalities in a case of POC as well as the differential diagnoses which can mimic POC.Case ReportA 23-year-old G2P0A1 (Gravida2, para0, abortion1) woman with a gestational age of around 12 weeks was referred for a routine first trimester ultrasound scan. The antenatal ultrasound scan showed a single, live, intrauterine gestation corresponding to a gestational age of 11 weeks and 5 days. The fetal heart was visualized outside the chest through a defect in the lower sternum in association with anterior diaphragmatic and ventral abdominal wall defects suggestive of thoraco-abdominal variety of ectopia cardis. There was a membrane covered, midline, abdominal wall defect at the base of the umbilical cord insertion containing the herniated abdominal organs including the liver, bowel loops and the ectopic cardia. There was a breach in the normal outline of the lower sternum indicating a sternal deficiency. The fetal pericardium was absent. The nuchal translucency was grossly increased. Pentalogy of Cantrell was diagnosed on ultrasound and the patient was explained about the poor prognosis of this condition. An informed consent was obtained after she opted for medical termination of pregnancy. The autopsy confirmed all the above mentioned ultrasound features.ConclusionsPentalogy of Cantrell (POC) is an extremely rare and complex syndrome of numerous fetal anomalies but should always be borne in the mind during the ultrasound evaluation of either of an omphalocele, ectopia cordis, distal sternal defect, pericardial defect, anterior diaphragmatic defect or intracardiac anomalies. Ultrasound is a valuable, safe, nonionizing, cost effective, widely available, and easily reproducible imaging tool for diagnosis of POC. Ultrasound should always be the primary mode of diagnosis in POC because although Magnetic resonance imaging (MRI) can help in better delineation of fetal anomalies, it does not significantly alter the course of the pregnancy or the management of POC.

Umbilical cord abnormalities in singleton pregnancies following assisted reproductive technologies (ART)

Umbilical cord abnormalities with clinical signs of cord compromise are frequently associated with fetal vascular malperfusion (FVM). Single umbilical artery (SUA) has been reported to be associated with high-grade FVM in fetal growth restriction but not in an unselected population; our study aimed to address this issue. Clinical and placental phenotypes of 55 consecutive placentas with SUA (Group 1) were compared with those of 655 placentas with 3-vessel umbilical cord (Group 2) from patients who were in the second half of their pregnancy. The placentas were histologically examined using hematoxylin and eosin (H&E) staining and CD 34 immunostaining. Several umbilical cord phenotypes and high-grade distal FVM, based on H&E staining and endothelial fragmentation by CD34 were significantly more common in Group 1, whereas decidual clusters of multinucleate trophoblasts were more common in Group 2. Notably, H&E staining or CD34 immunostaining evaluated separately showed that high-grade distal FVM was more common in Group 1 than in Group 2, but the difference was not statistically significant. SUA predisposes to remote, advanced, and recent high-grade distal villous FVM, with a pathogenesis partly different from that of stasis-induced FVM, likely related to fetal anomalies associated with SUA.

Ectopia cordis (EC) is the presence of a live, beating heart outside the thorax and is one of the most unique congenital anomalies. EC has been a weak association noted with trisomy 18 and a few cases have been associated with other chromosomal abnormalities. Pentalogy of cantrell (PC) is a rare congenital syndrome of abdominal wall defect, lower sternal defect, diaphragmatic pericardial defect, anterior diaphragmatic defect, and intracardiac abnormalities. It has a rare frequency of about 1/100,000 births. The hallmark of this syndrome is an omphalocele associated with EC. Only a few patients with the full spectrum of the pentalogy have been described. Only very few patients survive attempts at surgical repair, the main causes of death being tachyarrhythmias, bradycardia, low blood pressure, rupture of the diverticulum, and heart failure. Early diagnosis is important about discuss the option of elective termination with the parents if intracardiac anomalies of incompatible with life are noted. We report two cases of PC diagnosed in early second trimester.

Surgical treatment of three cases of Cantrell's syndrome

A patient with Cantrell's syndrome is presented with ectopia cordis, ventricular septal defect and a left ventricular as well as a right ventricular diverticulum. One-stage correction was performed with resection of both diverticula. Closure of the ventricular septal defect was complicated due to exposure problems as a result of the malposition of the heart. Although the presentation of Cantrell's syndrome can be variable, one-stage repair is technically feasible and should be considered as the treatment of choice in this rare syndrome.