In more extreme cases, the feces consolidate into hard masses inside the colon, called fecalomas (literally, fecal tumor), which can require surgery to be removed.

A genetic predisposition to Hirschsprung's disease has been linked to chromosome 13 where a missense mutation at an ultraconserved region impairs functionality of the W276C receptor.

[citation needed] In patients with HIV/AIDS, cytomegalovirus (CMV) colitis is the leading cause of toxic megacolon and emergency laparotomy.

Chagas disease can also be acquired congenitally, through blood transfusion or organ transplant, and rarely through contaminated food (for example garapa).

The Austrian-Brazilian physician and pathologist Fritz Köberle was the first to propose the neurogenic hypothesis based on the documented destruction of the myenteric plexus in the walls of the intestinal tracts of Chagas patients.

In this, the destruction of the autonomic nervous system innervation of the colon leads to a loss of the normal smooth muscle tone of the wall and subsequent gradual dilation.

His research proved that, by extensively quantifying the number of neurons of the autonomic nervous system in the Auerbach's plexus, that:[citation needed] Why T. cruzi causes the destruction, however, remains to be determined.