PENTALOGY OF CANTRELL. A STILLBIRTH CASE REPORT

Introduction: Pentalogy of Cantrell is a rare congenital disorder characterized by midline birth anomalies. Its embryological origins are related to anomalies of the abdominal wall that prevent the closure of the thorax. Its etiology is not yet clear, but it has been associated with a failure of migration of the lateral plate mesoderm to the midline. Case description: A stillbirth at 25.2 weeks of gestation diagnosed with pentalogy of Cantrell. The mother was a 14-year-old teenager with no relevant history of disease. An obstetric ultrasound was performed at 19 weeks of gestation and revealed findings suggestive of pen - talogy of Cantrell. The mother was informed of the potential risks and future complications for the fetus, yet she chose to continue with the pregnancy. At 25.2 weeks of gestation, the mother went to the emergency department due to pain in the hypogastrium accompanied by moderate vaginal bleeding and absence of fetal activity. Once fetal death was confirmed by ultrasound, labor was induced, resulting in stillbirth with anencephaly, thoracic hypoplasia, gastroschisis, and eventration of the liver. Conclusions: Adequate antenatal care, including strict ultrasound follow-up, is essential to detect future complications in the fetus; to provide advice on possible malformations incompatible with life, such as pentalogy of Cantrell; and to determine the best therapeutic approach.

Conclusiones. La realización de adecuados controles prenatales, en los cuales se realice un seguimiento ecográfico estricto, es fundamental para detectar futuras complicaciones en el feto; brindar asesoría sobre posibles malformaciones que sean incompatibles con la vida, como la pentalogía de Cantrell, y establecer las mejores alternativas de manejo. This is a rare disorder considering that only about 250 cases have been reported worldwide (4). Thus, it is a rare syndrome with an estimated incidence that varies from 1 cases per 65 000 to 200 000 live births in the different reported series (5-7). Its spectrum is variable and depends on the five basic defects that define it: a midline supraumbilical abdominal wall defect, defect of the lower sternum, defect of the anterior diaphragm, defect in the pericardium, and intra-cardiac defects (8).

INTRODUCTION
As described by Mărginean et al. (9), pentalogy of Cantrell was classified by Toyama (10) into three classes according to the number of defects in each patient.
Class 1 or definitive diagnosis has all 5 defects; class 2 or probable diagnosis involves 4 defects; and class 3 or incomplete expression comprises 3 defects.
Pentalogy of Cantrell or thoracoabdominal syndrome is characterized by the variable association of midline body defects with thoracoabdominal wall defects and its differential diagnosis is limb-body wall complex. Both conditions are of unknown cause and early origin but can be explained by an abnormal mesoderm development (11).
The available literature on pentalogy of Cantrell is scarce, mainly because it is a rare disease with great variability in its signs and symptoms of presentation.
Reports on this subject are therefore a valuable resource, as they can serve as a basis for future research (12).
Periodic obstetric ultrasound is recommended to detect and treat fetal anomalies since it allows providing optimal perinatal care, considering that approximately half of structural anomalies can be detected in the first trimester. Some of anomalies include anencephaly, abdominal wall defects, holoprosencephaly, and cystic hygromas. However, due to the stages of embryonic development of some organs, it should be kept in mind that certain anomalies are observed at a later gestational age. Similarly, it is worth noting that, as stated by Saldarriaga-Gil et al. (13), the second trimester is the best stage for study to identify fetal structural anomalies.
The following is a case of pentalogy of Cantrell associated with craniofacial, limb and reproductive system defects, which was suspected by ultrasound at week 19 of gestation and confirmed postmortem. This is the seventh case of this anomaly reported in Colombia in the last 10 years and the second case in a female patient (8,9,(14)(15)(16)(17).

Stillbirth of 25.2 weeks in whom multiple malformations were identified at 19
weeks of gestation via obstetric ultrasound, leading to the suspicion of a diagnosis of pentalogy of Cantrell. The mother was a 14-year-old mestizo girl from the rural area of La Sierra, department of Cauca, Colombia. No degree of consanguinity with the father was determined, but it was established that this was the mother's first pregnancy.
The first antenatal check-up was carried out in September 2019, when the mother was 19.4 weeks pregnant, and the laboratory tests ordered at that time and left ovary agenesis (Figures 1, 2, 3). The morphological detail of the images highlights the midline deviation in the face (Figure 1).   During the internal examination of the fetus, it was noted that hypoplasia of the thoracic cage was predominant with asymmetry on the right side and that the diaphragm separated the thoracoabdominal region, although it was displaced to the right and attached to the Glisson's capsule in the right lobe. It was also found that the liver protruded from the abdominal wall and that the area below the thoracic cage was adjacent to the psoas muscles, which were fused. The lungs     It was also evident that the reproductive system of the fetus was not fully formed and consisted of a uterus, right ovary and fallopian tubes hypoplasia, and agenesis of the left ovary ( Figure 7).

DISCUSSION
Pentalogy of Cantrell is a poorly described syndrome, but it has characteristic findings that allow to establish its diagnosis. Such findings comprise five basic defects: Pentalogy of Cantrell is also characterized by damage to the amnion that may produce fiber-like bands that limit the development of the fetus, causing constriction on already formed structures (16,17). In the present case, a sternal defect with hypoplasia of the right side of the thoracic cage and thoracoabdominal midline defects, such as gastroschisis and liver eventration, were observed.
Likewise, it was established that the fetus had ectopia cordis, although no pericardium defects or intracardiac anomalies were found, which does not rule out the diagnosis of pentalogy of Cantrell (10) because it has been proposed that this disorder has a wide spectrum of presentation, and its characteristics depend on the stage of development in which the defects occur (4).

Some of the causes described for pentalogy of Cantrell include aneuploidies
such as trisomies 13 and 18; viral infections; mother's intake of teratogenic agents such as thalidomide, warfarin, and quinidine; vitamin A deficiency in the mother during pregnancy; and some type of familial tendency, with an X-linked dominant inheritance pattern and alteration of the region Xq25-Xq26,1, which is a characteristic of thoracoabdominal syndrome (8,15). However, no association with factors predisposing to malformations was evident in the present case. It should be noted that the patient did not undergo karyotype testing because the mother was young and reported no medical, pharmacological or intoxication history.
Pentalogy of Cantrell is more prevalent in men, with a 1.35:1 ratio (22,23), so this case is of great interest.
One of the described causes of pentalogy of Cantrell is amniotic rupture in cases of ectopia cordis (9), which was evidenced in the case reported here.
Routine ultrasounds performed during antenatal checkups (between 12 and 14 weeks and 19 to 24 weeks of gestation) are extremely helpful in diagnosing pentalogy of Cantrell (19,24). When this disease is suspected in the first trimester of gestation, it may be necessary to carry out complementary studies such as fetal echocardiogram, magnetic resonance imaging and biopsy of the chorial villi, which allows for G-or Q-banding karyotype testing. Such studies are essential, as they allow the identification of the full spectrum of disease presentation and offer the best advice regarding prognosis and follow-up (25). Moreover, early detection of congenital defects allows to offer interdisciplinary support from the beginning of pregnancy, as well as assistance in decision-making about anomalies incompatible with life.
Finally, it is important to mention that during autopsies it is essential to make a detailed macroscopic and microscopic documentation of the findings, that is, a complete record of the malformations of the body must be made so that this, together with the pathologist's report, allows to establish the diagnosis that caused the death. In the present case, the findings corroborated at the autopsy highlight the importance of performing this procedure in cases of multiple congenital anomalies, as it allows the family and even the scientific community to learn about the complications that led to the termination of a pregnancy (26-28).

CONCLUSIONS
Adequate antenatal care, including strict ultrasound follow-up, is essential to detect future complications in the fetus, as well as to provide advice on possible malformations incompatible with life, such as pentalogy of Cantrell, and to determine the best therapeutic approach. Furthermore, autopsies on fetuses with multiple congenital anomalies are indispensable because, as in this case, they allow for the identification of alterations not detected on ultrasound or external physical examination.

ETHICAL CONSIDERATIONS
The informed consent of the legal guardian of the 14-year-old girl who gave birth to the stillborn that is the subject of this report was obtained.

CONFLICT OF INTEREST
None stated by the authors.