Address correspondence to William J. Meyer, MD, Dept. of Ob-Gyn, Maternal-Fetal Medicine, Univ. of Illinois at Chicago, 840 South Wood St. M/C 808, Chicago, IL 60612-4324, Ph: 312-996-7300; Fax; 312-996-4238

Synonyms: Ectopia cordis, ectocardia, exocardia.

Definition: A rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. Depending on the position of the heart, ectopia cordis has been categorized into four types: cervical, thoracic, thoracoabdominal and abdominal2,3.

Prevalence: 0.079:10,0001.

Etiology: Unknown.

Pathogenesis: Predominant theories include: 1) primary failure of descent and midline fusion of the lateral body folds; 2) early rupture of chorion and/or yolk sac causing failure of midline fusion; 3) amniotic band syndrome.

Associated anomalies: CNS, facial, intracardiac (80%), pericardial, sternal clefting, abdominal and gastrointestinal (see Table 1).

Differential diagnosis: Cyllosomas, amniotic band syndrome, Pentalogy of Cantrell.

Prognosis: Generally very poor depends on the presence and severity of intracardiac and other associated abnormalities.

Recurrence risk: Not increased.

Management: Includes a careful search for associated anomalies and chromosomal analysis. A non-aggressive approach is recommended as ectopia cordis is associated with a very poor prognosis.

MESH Ectopia Cordis, Cardiovascular anomalies, congenital BDE 0335 POS 3248 ICD9 746.8 CDC 746.880

Introduction

Ectopia cordis is a rare congenital malformation in which the heart is located partially or totally outside the thoracic cavity. Ectopia cordis may occur as an isolated malformation or it may be associated with a larger category of ventral body wall defects that affect the thorax, abdomen or both. We present a case of ectopia cordis associated with severe kyphoscoliosis and complete ventral body wall defect.

Case report

A 20-year-old black G1P0 patient was referred after a routine dating ultrasound revealed an abdominal wall defect. The patient had no prenatal care prior to this time and was 36 weeks by dates. Our examination revealed a single fetus with BPD and femur length measurements consistant with 31 and 29 weeks gestational age respectively. Multiple congenital anomalies were seen including: thoracic ectopia cordis (fig. 1), diaphragmatic hernia, ventral abdominal wall defect with exstrophy of the liver, intestines, kidney and bladder (fig. 2), scoliosis and bilateral multicystic kidneys. No craniofacial or intracardiac abnormalities were detected and the cardiac outflow tracts appeared normal. Amniotic fluid was decreased as was fetal motion. The umbilical cord and placenta were normal in appearance and location. A diagnosis of ectopia cordis associated with ventral body wall defect was made.

The family history was negative for congenital anomalies or genetic abnormalities and the patient denied exposure to drugs or toxins. The patient was counseled regarding the poor prognosis for this fetus and a non-aggressive management plan was agreed upon. Genetic amniocentesis was performed and revealed a 46,XX,16qh+ karyotype. Ten days after the amniocentesis, rupture of membranes occurred and the patient went into spontaneous labor. The infant, a 2000g female, was born vaginally and expired two hours after delivery. The findings at autopsy included severe left kyphoscoliosis with marked deformity of the chest (extreme narrowing of left thoracic cavity without organs); asymmetrical left chest wall and abdominal wall defect with evisceration of the heart, left lung, liver, stomach, small and large intestines, left kidney, uterus and bladder; abnormal position of a malformed left arm with partial absence of forearm and absence of hand (fig. 3). There were no craniofacial anomalies. The intracardiac structures and outflow tracts were normal. The placenta and umbilical cord were unremarkable.

The parents were counseled regarding the karyotypic abnormality and parental karyotyping was recommended. They have thus far refused any genetic testing.

Discussion

Diagnosis

Ectopia cordis is a very rare anomaly with an estimated prevalence of 0.079/10,000 births and may occur more frequently in females¹. The prenatal diagnosis is easily made with ultrasound by visualizing the heart outside the thoracic cavity. Four types of ectopia cordis have been described according to the position of the heart; anterior to the sternum (thoracic: 65%), between the thorax and abdomen (thoracoabdominal: 20%), within the abdomen (abdominal: 10%) or in the neck (cervical: 5%)^2,3. The thoracic and thoracoabdominal types are most common followed by the abdominal and cervical types4. The combination of thoracoabdominal ectopia cordis, lower sternal defect, anterior diaphragmatic hernia, midline supraumbilical defect along with pericardial and intracardiac defects constitute the Pentalogy of Cantrell^5,6.

Pathogenesis

Embryologically, the development of the ventral body wall begins after the eighth day of embryonic life with differentiation and proliferation of a mesodermal layer between the trophoblast and the endoderm. Lateral migration of the paired mesoderm then occurs. At about 16 days, the mesoderm splits laterally into an outer somatic layer and an inner splanchnic layer with the coelomic cavity interspaced between. Ventromedial folding of the paired mesodermal layers gives rise to the thoracic/abdominal walls, the sternum (somatic mesoderm), and to the septum transversum of the diaphragm, pericardium and epimyocardium (splanchnic mesoderm) (fig. 4). The heart originally develops in a very cephalad location and reaches its definitive position by the lateral folding and ventral flexing of the embryo at about 16-17 days of development. Midline fusion and formation of the thoracic and abdominal cavities is complete by the 9^th embryonic week^5,7 (fig. 5).

Complete or incomplete failure of midline fusion at this embryonic stage can result in a variety of disorders ranging from isolated ectopia cordis to complete ventral evisceration. Early rupture of the chorion and/or yolk sac causing compression of the thorax preventing midline fusion has been proposed as mechanical cause of these defects as has early rupture of the amnion with formation of fibrous amniotic bands^8-10. Ectopia cordis has been attributed to intrauterine drug exposure in animal models, a finding which has not been confirmed in humans^11,12.

Associated anomalies

Ectopia cordis is frequently associated with other congenital defects involving multiple organ systems (Table 1).

Table 1: Anomalies associated with ectopia cordis^{4,5,8,9,13,14}

Ventricular septal defect and Tetralogy of Fallot are the most common intracardiac defects while omphalocele is the most common abdominal wall defect associated with ectopia cordis.

While ectopia cordis is generally considered to be an isolated, sporadic malformation, there have been a number of reports linking it to chromosomal abnormalities. Reported karyotypic abnormalities include trisomy 18^15-18, Turner syndrome¹⁹ and 46,XX,17q+20. The karyotype on the present case, 46,XX,16qh+, has to our knowledge not previously been reported in association with ectopia cordis. It may represent a normal familial variant of chromosome 16, and parental testing would be needed to ascertain the normality of this. However, both parents have refused such testing. In general, chromosomal analysis is indicated in a patient with ectopia cordis diagnosed prenatally especially if other anomalies are also identified.

Management

The prognosis is generally poor and depends on the severity of intracardiac malformations and the presence of associated abnormalities. Most infants are stillborn or die within the first hours or days of life. Attempts at surgical correction have been largely unsuccessful due to the extent of the associated anomalies. Recommendations for surgical management include immediate covering of the exposed heart and abdominal contents with a silastic prosthesis, as well as full evaluation and correction of any intracardiac defects prior to replacement of abdominal contents^21,22. The procedure often fails secondary to kinking of the great vessels or mechanical compression of the heart resulting in decreased cardiac output^23-26.

Obstetrical management should include a careful search for associated anomalies, especially cardiac, and assessment of fetal karyotype. Pregnancy termination prior to viability and a nonaggressive management in the third trimester should be considered and discussed with the parents. As this is considered a sporadic event, the recurrence risk is not elevated over that of the general population.

References

1. Khoury MJ, Cordero JF, Rasmussen S: Ectopia cordis, midline defects and chromosome abnormalities: An epidemiologic perspective. Am J Med Genet 30:811-817, 1988.

2. Blatt ML, Zeldes M: Ectopia cordis: Report of a case and review of the literature. Am J Dis Child 63:515, 1942.

3. Byron F: Ectopia cordis: report of a case with attempted operative correction. J Thorac Surg 17:717-722, 1949.

4. Leca F, Thibert M, Khoury W, Fermont L, Laborde F, Dumez Y: Extrathoracic heart (ectopia cordis). Report of two cases and review of the literature. Int J Cardiol 22:221-228, 1989.

5. Cantrell JR, Haller JA, Ravitch MM: A syndrome of congenital defects involving the abdominal wall, sternum, diaphragm, pericardium, and heart. Surg Gynecol Obstet 107:602-614, 1958.

6.Toyama WM: Combined congenital defects of the anterior abdominal wall, sternum, diaphragm, pericardium, and heart: a case report and review of the syndrome. Pediatr 50:778-792, 1972.

7. Kanagasuntheram R, Verzin JA: Ectopia cordis in man. Thorax 17:159, 1962.

8. Kaplan LC, Matsuoka R, Gilbert EF, Opitz JM, Kurnit DM: Ectopia cordis and cleft sternum: Evidence for mechanical teratogenesis following rupture of the chorion or yolk sac. Am J Med Genet 21:187-199, 1985.

9. Van Allen MI, Myhre S: Ectopia cordis thoracalis with craniofacial defects resulting from early amnion rupture. Teratology 32:19-24, 1985.

10. Bieber FR, Mostoufi-zadeh M, Birnholz JC, Driscoll SG: Amniotic band sequence associated with ectopia cordis in one twin. J Pediatr 105:817-819, 1984.

11. Jaffee OC, Jaffee AL: Ectopia cordis in the chick embryo heart: An experimental study. Teratology 41:737-742, 1990.

12. Barrow MV, Willis LS: Ectopia cordis (ectocardia) and gastroschisis induced in rats by maternal administration of the lathyrogen, beta-aminopropionitrile (BAPN). Am Heart J 83:518-526, 1972.

13. Ghidini A, Sirtori M, Romero R et al. Prenatal diagnosis of pentalogy of Cantrell. J Ultra Med 7:567, 1988.

14. Muller G, Schaller A: Ectopia cordis cervicalis: A case report. Teratology 25:277-281, 1982.

15. Bick D, Markowitz RI, Horwich A: Trisomy 18 associated with ectopia cordis and occipital meningocele. Am J Med Genet 30:805-810, 1988.

16. Fox JE, Gloster ES, Mirchandani R: Trisomy 18 with Cantrell Pentalogy in a stillborn infant. Am J Med Genet 31:391-394, 1988.

17. King CR: Ectopia cordis and chromosomal errors. Pediatrics 66:328, 1980.

18. Soper SP, Roe LR, Hoyme HE, Clemmons JJW: Trisomy 18 with ectopia cordis, omphalocele, and ventricular septal defect: Case report. Pediatr Pathol 5:481-483, 1986.

19. Garson A, Hawkins EP, Mullins CE, Edwards SB, Sabiston DC, Cooley DA: Thoracoabdominal ectopia cordis with mosaic Turner"s syndrome: Report of a case. Pediatrics 62:218-221, 1978.

20. Say B, Wilsey CE: Chromosome aberration in ectopia cordis (46,XX,17q+). Am Heart J. 95:274-5, 1978.

21. Harrison MR, Filly RA, Stanger P, De Lorimier AA: Prenatal diagnosis and management of omphalocele and ectopia cordis. J Pediatr Surg 17:64-66, 1982.

22. Dobell ARC, Williams HB, Long RW: Staged repair of ectopia cordis. J Pediatr Surg 17:353-8, 1982.

23. Glass RB, Fernbach SK: Case report: Ectopia cordis and the radiographic changes of a new surgical repair technique. Clinical Radiology 38:443-4, 1987.

24. Todros T, Presbitero P, Montemurro D, Levis F: Prenatal diagnosis of ectopia cordis. J Ultrasound Med 3:429-431, 1984.

25. Jones AF, McGrath RL, Edwards SM, Lilly JR: Immediate operation for ectopia cordis. Ann Thorac Surg 28:484-486, 1979.

26. Dougall AJ, Grant JC: Ectopia cordis: Report of a case with attempted operative correction. J Pediatr Surg 8:959-960, 1973.