Pentalogy of Cantrell or one of its variants

Findings

Case 1. On ultrasound, the 24-week-gestational-age fetus was noted to have a midline umbilical wall defect with a herniated sac containing the liver and bowel (Figure 1A) with the umbilical cord attached at the apex of the sac, which was suggestive of an omphalocele. The ultrasonographic examination also revealed a sternal defect with ectopia cordis, scoliosis, and clubfoot. The head of the fetus was hyperextended, and the face was seen touching the anterior wall of the uterus, thus making the evaluation of the face difficult. The patient had been notified of the prognosis of her fetus' condition and was offered various options, but she chose to continue her pregnancy until labor occurred naturally.

Labor occurred spontaneously and a stillborn male weighing 1500 g was delivered at 32 weeks of gestation, 8 weeks after the prenatal ultrasound examination. Autopsy findings (Figure 1B) revealed an omphalocele with herniation of the bowel and liver, a midline sternal defect with ectopia cordis, a right-sided clubfoot, scoliosis, a bilateral cleft lip, and a midline cleft palate. Autopsy features thus confirmed the sonographic features and revealed a cleft palate, which had not been detected on sonography because the head of the fetus was hyperextended.

Case 2. The routine prenatal ultrasonogram showed that this 25.5-week gestational fetus was alive and had an omphalocele containing herniated bowel and liver (Figure 2) and a sternal defect with ectopia cordis. The fetus' prognosis and treatment options were explained to the patient. She chose to have labor induced. Three days after the ultrasound examination, a male stillborn neonate weighing 700 g was delivered.

Autopsy findings revealed an omphalocele with herniation of the bowel and liver and a midline sternal defect with ectopia cordis. Autopsy features thus confirmed the sonographic features in this second case as well. This fetus did not have associated cleft lip or palate, and there was no evidence of clubfoot.

Discussion

In both of these cases, imaging and autopsy findings of midline supraumbilical abdominal wall defects, defects in the pericardium, and defects of the lower sternum clearly indicate a diagnosis of pentalogy of Cantrell or one of its variants.

In 1958, Cantrell et al¹ described a syndrome in which a ventral (anterior) diaphragmatic hernia occurred in association with an omphalocele. This syndrome, called the pentalogy of Cantrell, consists of the following: A deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, congenital intracardiac abnormalities, and a defect of the lower sternum. Few variants of this syndrome have been described.^1,2

The association of sternal fusion defects with various cardiac, diaphragmatic, and anterior body wall defects represents a continuum of developmental anomalies that includes the pentalogy of Cantrell and ectopia cordis. Ectopia cordis (extrathoracic heart) is a rare malformation at the most severe end of the spectrum of anterior body wall defects involving sternal fusion abnormalities.³

This spectrum of defects is more appropriately categorized as a "midline developmental field complex" and, as such, is causally heterogeneous. Evidence for this heterogeneity is suggested by the occasional occurrence of this complex in chromosomal and other multiple malformation syndromes.⁴

Variants of the pentalogy of Cantrell have been described by Toyama.² The following classification for the pentalogy of Cantrell was suggested:

(A) Diagnosis certain if all 5 defects are present;

(B) Diagnosis probable if 4 defects (including intracardiac and ventral abdominal wall) are present; and

(C) Diagnosis is incomplete if variable combinations of defects are present (always including a sternal abnormality).²

The embryologic defects responsible for the variety of abnormalities present in the pentalogy of Cantrell are of mesodermal origin. The diaphragmatic and pericardial defects are closely related to either the total or partial failure of septum transversum development, whereas the cardiac abnormalities result from the faulty development of the epimyocardium. The sternal and abdominal wall defects represent faulty migration of these mesodermal primordial structures. It is thought that these developmental abnormalities occur from approximately day 14 to 18 of embryonic life.⁵ The failure of this process is believed to occur because of one or more of the following:

1. Vascular dysplasias resulting in vascular steal phenomena.
2. Mechanical teratogenesis by amnion rupture, tearing, and adhering; tissue band adherence causing pressure necrosis and incomplete morphogenesis; or mechanical compression secondary to rupture of the chorion or the yolk sac.

3. Genetic mutation, either idiopathic or due to viral infection in the early first trimester or drugs given to the mother.⁶ In the first case reported here, which included associated bilateral cleft lip and a midline cleft palate, we believe that this anomaly was due to a migration defect in the primordial mesoderm of the face, which accompanied the ventral body wall defects in the fetus.

Many other associations have been found with pentalogy of Cantrell, which include the following: Amniotic band syndrome with limb anomalies, structural cardiac defects with pericardial effusion, exencephaly, cystic hygroma, infraumbilical defects with cloacal and bladder exstrophy, and bilateral inguinal hernias. Concurrent structural and/or chromosomal abnormalities may complicate up to 50% to 75% of cases presenting with omphaloceles and, thus, they are indicators for antenatal invasive testing.^7,8 Omphalocele should be considered pathologic only if it persists beyond 14 weeks or if its maximum diameter exceeds 1 cm in the first trimester of pregnancy.^9,10 Few cases have been reported in which the pregnancy was continued until term and the fetus delivered by induction of labor. A number of corrective surgeries have been performed on such neonates for correction of defects, after which normal growth was achieved by the age of 2 to 3 years.

CONCLUSION

Pentalogy of Cantrell is a spectrum of congenital anomalies, from fatal to nonfatal, that must therefore be adequately evaluated for appropriate prenatal counseling and postnatal management of individual cases.

1. Cantrell JR, Haller JA, Ravitch MM. A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium and heart. Surg Gynecol Obstet. 1958;107:602-614.
2. Toyama WM. Combined congenital defects of the anterior abdominal wall, sternum, diaphragm, pericardium and heart: A case report and review of the syndrome. Pediatrics. 1972;50:778-792.
3. Martin RA, Cunniff C, Erickson L, Jones KL. Pentalogy of Cantrell and ectopia cordis, a familial developmental field complex. Am J Med Genet.1992;42:839-841.
4. Baker ME, Rosenberg ER, Trofatter TF, et al. The in utero findings in twin pentalogy of Cantrell. J Ultrasound Med.1984;3:525-527.
5. Siles C, Boyd PA, Manning N, et al. Omphalocele and pericardial effusion: Possible sonographic markers for the pentalogy of Cantrell or its variants. Obstet Gynecol. 1996;87(5 Pt 2):840-842.
6. Shah HR, Patwa PC, Pandya JB, et al. Antenatal ultrasound diagnosis of a case of 'Pentalogy of Cantrell' with common cardiac chambers: Case report. Ind J Radiol Imag. 2000;10:99-101.
7. Benacerraff VR, Saltzman DH, Estroff JA, Frigoletto FD Jr. Abnormal karyotype of fetuses with omphalocele: Prediction based on omphalocele contents. Obstet Gynecol. 1990;75(3 Pt 1):317-319.
8. Gilbert WM, Nicolaides KH. Fetal omphalocele: Associated malformations and chromosomal defects. Obstet Gynecol.1987;70:633-635.
9. Cullinan JA, Nyberg DA. Fetal abdominal wall defects. In: Rumack CM, Wilson SR, Charboneau JW, eds. Diagnostic Ultrasound. 2nd ed. St. Louis, MO: Mosby-Year Book, Inc.; 1998:1167-1169.
10. Cyr DR, Mack LA, Schoenecker SA, et al. Bowel migration in the normal fetus: US detection. Radiology.1986;161:119-121.

Prepared by Paritosh C. Khanna, MD, DMRE; Alpa Bharati, MD; and Suleman A. Merchant, MD, DMRD, Department of Radiology, LTMG Hospital, Sion, Mumbai, India.