# Cantrell Syndrome and the One Health Perspective: A Unified Review of Human and Comparative Cases

## TL;DR

Cantrell syndrome is a rare congenital disorder with varied symptoms, and this study reclassifies cases to improve understanding and diagnosis using a One Health approach.

## Contribution

The study introduces a unified classification system for Cantrell syndrome cases, revealing many previously labeled as 'classic' are actually partial or atypical forms.

## Key findings

- Midline defects are most common in Cantrell syndrome, with 92.7% of cases involving these types of anomalies.
- Cardiac anomalies are universal in Cantrell syndrome, with septal defects being the most frequent.
- A One Health perspective highlights shared developmental vulnerabilities across mammalian species affected by Cantrell syndrome.

## Abstract

Cantrell syndrome (CS) is a rare condition affecting the development of the chest and abdominal wall, diaphragm, pericardium, sternum, and heart. Since the syndrome was first described in 1958, only 165 well-documented human cases have been reported, and they demonstrate a wide range of presentations. Some individuals have all five characteristic defects, while others exhibit partial or atypical combinations. Most cases involve midline defects above the umbilicus, though a few present with lateral openings or atypical patterns. Heart defects were present in every case, most often involving openings in the heart’s septa. Our review shows that many cases previously thought to represent the full “pentalogy” are better understood as partial or atypical forms. This study places CS within a broader developmental context by carefully examining the anatomy of the body wall and umbilical cord and comparing human findings with similar conditions in animals. The similarities between species highlight shared biological vulnerabilities and support a one health approach to studying congenital malformations.

Cantrell syndrome (CS) is a rare congenital disorder involving defects in the thoraco-abdominal midline, the diaphragm, the pericardium, the sternum and the heart. Since the initial description of the syndrome, 165 well-documented cases in humans have been reported, demonstrating substantial heterogeneity ranging from complete pentalogy to partial or atypical variants. A systematic review classified body wall defects and associated anomalies into nine categories, which are fully described in the manuscript. The categories include midline defects (UThAb, SUThAb, UAb, SUAb, SUICD, and UH), lateral defects (ThLAb and StLAb), and special cases. Each case was reassessed for umbilical cord status, body wall morphology, cardiac anomalies and additional malformations. Midline defects predominated (153 out of 165 cases, 92.7%), with supraumbilical variants being the most frequent. Umbilical hernias formed a distinct subgroup of ten cases. Lateral defects were uncommon (9 cases, 5.5%) and typically presented as thoracogastroschisis or lateral thoracoabdominoschisis. These defects were often associated with normal umbilical cords. Cardiac anomalies were universal, with ventricular and atrial septal defects being the most common findings. Reclassification revealed that many cases originally labeled as ‘classic pentalogy of Cantrell’ were more accurately classified as partial or atypical forms. This unified framework improves epidemiological understanding and diagnostic precision. From a One Health perspective, it underscores CS as a shared developmental vulnerability across mammalian species.