Pentalogy of Cantrell in Two Neonate Littermate Puppies: A Spontaneous Animal Model Suggesting Familial Inheritance

Abstract

Developmental anomalies are an important cause of stillbirth and early perinatal death in companion animals. Many of these disorders remain poorly understood and provide an opportunity as a spontaneous animal model for human disease. Pentalogy of Cantrell is a rare congenital syndrome described in human neonates. It is a ventral midline closure defect with a proposed familial inheritance in humans. This syndrome involves five defects, including the thoracoabdominal wall, sternal, diaphragmatic, pericardial and cardiac malformations. Diverse expressions of these defects have been described in humans and sporadically in domestic animals. This severe syndrome commonly harbors a poor prognosis, posing an ethical and surgical dilemma. To better understand this syndrome and its presentation in dogs, we describe two rare cases of Pentalogy of Cantrell in a litter of papillon dogs. The affected puppies had anomalies compatible with the Pentalogy of Cantrell, including thoracoabdominal schisis, ectopia cordis, sternal cleft, pericardial agenesis, and diaphragmatic defects. The diagnosis was confirmed by advanced imaging (computed tomography) and postmortem examinations. The family history of this litter was explored and other cases in domestic animals were reviewed. This is the first report of the complete Pentalogy of Cantrell with ectopia cordis in the dog and the only report on papillons. Similar to human cases, possible familial inheritance and suspected male gender bias were observed. Further research on this novel animal model, its pathogenesis and its hereditary basis, may be helpful in better understanding this rare developmental disorder.

Keywords: canine; congenital; ectopia cordis; gastroschisis; midline closure defect; papillon; rare disease; thoracoabdominal syndrome.

Figure 1

Presentation of midline defects in affected papillon puppies. (A) Case 1 with ectopia cordis (arrow) and extrusion of most abdominal viscera (arrowhead: liver). (B) Computed tomography (CT) of Case 1 highlighting lack of sternum, missing right radial bone (large arrow) and extranumerary right limb (small arrow). (C,D; ex situ and CT) Case 1 with an extranumerary limb (arrow[s]). (E) Case 2 with a thoracoabdominal defect; note the slightly fused cranial sternum compared to Case 1.

Figure 2

Cranial (thoracic) and caudal (abdominal) boundaries of midline schisis in affected papillon puppies. Left: Case 1 (A,C), right: Case 2 (B,D). Horizontal lines represent parallel anatomical markers (neck, elbow, knee and caudal midline levels). Stars represent the extent of the cranial (A,B) and caudal (C,D) midline defects.