Visceral myopathy: clinical syndromes, genetics, pathophysiology, and fall of the cytoskeleton

Am J Physiol Gastrointest Liver Physiol. 2021 Jun 1;320(6):G919-G935. doi: 10.1152/ajpgi.00066.2021. Epub 2021 Mar 17.

Abstract

Visceral smooth muscle is a crucial component of the walls of hollow organs like the gut, bladder, and uterus. This specialized smooth muscle has unique properties that distinguish it from other muscle types and facilitate robust dilation and contraction. Visceral myopathies are diseases where severe visceral smooth muscle dysfunction prevents efficient movement of air and nutrients through the bowel, impairs bladder emptying, and affects normal uterine contraction and relaxation, particularly during pregnancy. Disease severity exists along a spectrum. The most debilitating defects cause highly dysfunctional bowel, reduced intrauterine colon growth (microcolon), and bladder-emptying defects requiring catheterization, a condition called megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). People with MMIHS often die early in childhood. When the bowel is the main organ affected and microcolon is absent, the condition is known as myopathic chronic intestinal pseudo-obstruction (CIPO). Visceral myopathies like MMIHS and myopathic CIPO are most commonly caused by mutations in contractile apparatus cytoskeletal proteins. Here, we review visceral myopathy-causing mutations and normal functions of these disease-associated proteins. We propose molecular, cellular, and tissue-level models that may explain clinical and histopathological features of visceral myopathy and hope these observations prompt new mechanistic studies.

Keywords: CIPO; MMIHS; cytoskeleton; visceral myopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytoskeleton / genetics*
  • Cytoskeleton / pathology
  • Humans
  • Intestinal Pseudo-Obstruction / diagnosis*
  • Intestinal Pseudo-Obstruction / genetics
  • Intestinal Pseudo-Obstruction / pathology
  • Muscle, Smooth / pathology*
  • Mutation