Pentalogy of Cantrell is an unusual form of abdominal wall defect that consists of five associated anomalies, including: (1) midline epigastric abdominal wall defect, (2) defect of the lower sternum, (3) deficiency of the anterior diaphragm, (4) defect in the diaphragmatic pericardium, and (5) intracardiac defects. This constellation of anomalies was first described by Cantrell et al. (1958), hence, the term pentalogy of Cantrell, although it has also been referred to as the Cantrell–Haller–Ravitch syndrome and peritoneal pericardial diaphragmatic hernia. Not every case will have all five factors and some cases may have associated anomalies, usually midline defects also such as cleft lip or palate, sirenomelia, exencephaly (Carmi and Boughman, 1992; Egan et al., 1993; Polat et al., 2005). Toyama suggested a classification scheme for pentalogy of Cantrell in which Class 1 included those cases in which the diagnosis was definite and all five defects were present. In Class 2, the diagnosis was probable with the presence of four defects including the pressure of intracardiac and ventral abdominal wall defects. In Class 3, there was incomplete expression and various combinations of defects including a sternal abnormality (Toyama, 1972). Although pentalogy of Cantrell has been used interchangeably with ectopia cordis, in their original description Cantrell et al. (1958) were careful to distinguish between these two anomalies (see Chapter 59).

Cantrell suggested that the defects in this syndrome fell into two groups by mechanism of embryologic development. In the first group, a developmental failure of mesoderm results in diaphragmatic, pericardial, and intracardiac defects. The diaphragmatic defect is a failure of the transverse septum to develop. The pericardial defect arises from the somatic mesoderm immediately adjacent to the region of the same layer from which the transverse septum develops. Defective development of one but not the other of these structures is possible only with highly specific loss of somatic mesoderm. This is rarely seen in pentalogy of Cantrell in which the diaphragmatic and pericardial defects occur together in most patients. The intracardiac lesions result from abnormal development of the epimyocardium, which is derived from the splanchnic mesoderm. While the resulting intracardiac defects vary, almost all include defects of the cardiac septa.

The second group of defects results from failure of the ventral migration of the periprimordial structures and includes the sternal defect and the epigastric omphalocele. All elements of the sternum are present, and the costocartilages connect with the cartilaginous plates, which represent the paired sternal anlagen with variable degrees of fusion. The sternal defect results not from an absence of sternal primordia but from the failure of paired sternal anlagen to complete migration. A similar failure of migration results in the abdominal wall defect. The normal layers of the ventral abdominal wall are present, but there is a lack of ventral migration of the myotomes. These patients have structurally normal rectus abdominus muscles that correctly attach to the pubic symphysis, but deviate laterally as they run cephalad to insert into the costal margins at the midclavicular line. This lack of migration is thought to be due to a defective development of the paramedian mesoderm.

The heart in pentalogy of Cantrell is normally positioned within the chest. In contrast, ectopia cordis is characterized by abnormal position of the heart outside of the chest (see Chapter 59). This becomes confusing, as classification systems for ectopia cordis list three types: cervical, thoracic, and thoracoabdominal, which is the same as pentalogy of Cantrell. Ectopia cordis may encompass partial or complete sternal defects, and invariably includes intracardiac anomalies, but does not include the pericardial, diaphragmatic, and abdominal wall defects seen in the pentalogy of Cantrell. Kanagusuntheram and Verzin (1962) suggested that ectopia cordis occurs as a result of excessive pericardial coelom formation and subsequent destruction of the transverse septum with rupture of the anterior body wall at 6 weeks of gestation (Kanagusuntheram and Verzin, 1962). Ravitch (1986) has suggested that the high frequency of major intrinsic cardiac defects with true ectopia cordis indicates that there is a primary defect in the splanchnic mesoderm responsible for cardiac development.

The primitive thoracic wall consists of somatopleura covering the ventral wall of the pericardial cavity. The ectodermal layer of the somatopleura forms the skin, but the remainder of the components of the body wall derive from invading dorsal mesoderm during the 6th week of gestation. The sternum appears as two parallel condensations of mesenchyme, the lateral sternal bands. A median cranial condensation, the presternum, appears independently. The lateral sternal bands fuse with the presternum cranially and with the tips of the ribs laterally. During the 7th week, the sternal bands begin fusing at their cephalic end and proceed caudally and cease by the 9th or 10th week.

The pentalogy of Cantrell is a rare association of anomalies with fewer than 100 cases having been reported (Craigo et al., 1992; Jochems et al., 2004). Due to the rarity of this condition, its incidence is difficult to accurately estimate. The incidence of the syndrome has been suggested to range between 1:65,000 to 1:200,000 (Martin et al., 1992; Vazquez-Jimenez et al., 1998). Carmi et al. (1993) reported five cases of pentalogy of Cantrell ascertained through the Baltimore– Washington population-based study of infants with congenital cardiovascular malformations, and estimated a regional prevalence of 5.5 cases for 1 million liveborn infants. The prevalence in fetuses is unknown (Aber-Yousef et al., 1987). African Americans may be more predisposed to developing pentalogy of Cantrell (Kousseff et al., 1996). Males appear more at risk with an incidence 2.7 times that of females (Egan et al., 1993). There have been five cases of pentalogy of Cantrell occurring in twins (Baker et al., 1984; Ghidini et al., 1988; Carmi and Boughman, 1992).

The most obvious feature of pentalogy of Cantrell is the epigastric omphalocele (Figure 61-1). There are reported cases with diastasis rectus without an omphalocele, which may be difficult to diagnose prenatally. The anterior diaphragmatic and pericardial defects are difficult, if not impossible, to discern sonographically. MRI may offer assistance in defining anterior diaphragmatic defects in some cases (Song and McLeary, 2000).

The three features of the pentalogy that may be most easily detected include the epigastric omphalocele, lower sternal defects, and intracardiac defects (Romero et al., 1988; Craigo et al., 1992).

Even if no other structural defects can be found, any fetus with an epigastric omphalocele should be evaluated for pentalogy of Cantrell, with particular attention paid to possible associated cardiac defects. The abdominal wall defect in pentalogy of Cantrell may vary from a very large omphalocele containing the stomach, liver, and apex of the heart to only widely displaced rectus abdominus muscles with skin covering the other defects and a ventral hernia.

The heart in the pentalogy of Cantrell is positioned within the fetal chest (Figure 61-2). If the heart is located outside the fetal chest, this indicates ectopia cordis (see Chapter 59). Even though positioned within the chest, there is a subtle shift in the cardiac axis in pentalogy of Cantrell. The heart is normally oriented horizontally, with the apex to the left. However, in this syndrome, the apex is oriented vertically, with the apex at the superior edge of the abdominal wall defect. Usually, but not invariably, the heart in the pentalogy of Cantrell has intracardiac anomalies. The most commonly observed is a ventricular septal defect (Table 61-1).