Pentalogy of Cantrell

Definition

The full pentad of the syndrome of pentalogy of Cantrell is rare and consists of the following five defects:

• 1.

  deficiency of the anterior diaphragm,

• 2.

  defect of the lower sternum,

• 3.

  midline supraumbilical abdominal wall defect,

• 4.

  defect in the diaphragmatic pericardium,

• 5.

  congenital intracardiac abnormality.

In 1972 Toyama suggested an alternative classification system to describe the more common variants of this syndrome :

• Class 1: definite diagnosis (all five defects present).

• Class 2: probable diagnosis (four defects present, including ventral wall abnormalities and cardiac defects).

• Class 3: incomplete expression (various combinations of defects present, including a sternal abnormality).

Skeletal and dermatologic manifestations have also been described in relation to this disorder, leading some to suggest that the term be replaced with hexalogy or heptalogy of Cantrell.

Prevalence and Epidemiology

The prevalence of pentalogy of Cantrell has been reported to range from 1 : 65,000 to 5.5 : 1 million live births. This wide range is secondary to the variation in classification of the syndrome and whether estimates are made using the strictest criteria (class 1) versus more liberal criteria (class 3). A 2 : 1 male predominance has been reported in some series.

Etiology, Pathophysiology, and Embryology

The etiology and pathogenesis for this syndrome is not well understood and is thought to be of a heterogeneous origin. On an embryologic basis, Cantrell et al. proposed that the association of defects is mesodermal in origin, occurring in the third week of embryonic life. Abnormal migration of splanchnic and somatic mesoderm with premature breakage of the vitelline sac results in a midline defect. Abnormal formation of the transverse septum of the diaphragm occurs because of abnormal migration of myoblasts; premature atrophy of the cardinal vein leads to associated pericardial defects.

Most reported cases of pentalogy of Cantrell are thought to be sporadic in occurrence; however, mutations in genes located on the X chromosome have been associated with ventral midline disruptions. An X-linked dominant inheritance pattern has been observed in some families. In such cases, the ventral midline is viewed as a developmental field, and embryologic disruptions in single genes involved in the development of this field are responsible for the wide range of midline defects. It is unclear whether pentalogy of Cantrell represents a separate entity as opposed to an extreme end of the spectrum of ventral midline disorders.

A responsible gene for this disorder has not yet been identified; however, a recent case report demonstrated a novel maternally-in herited microduplication of chromosome 15q21.3 on postnatal chromosomal microarray of a newborn with a prenatal diagnosis of pentalogy. This region includes the gene ALDH1A2 , which encodes for retinaldehyde dehydrogenase type 2, an enzyme with a critical role in normal cardiac and diaphragm development, thereby demonstrating a biologically plausible association with this disorder.