Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy

Abstract

We investigated small- and large-bowel specimens of three newborn infants presenting with the clinical and radiological symptoms of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Conventional histological staining revealed marked thinning of the longitudinal muscle layer. Electron-microscopic investigations showed typical "central core" vacuolic degeneration of smooth-muscle-cells combined with proliferation of col lagen fibres. The expression of alpha-smooth-muscle actin was absent or markedly reduced in the circular and longitudinal muscle layers and muscularis mucosae compared to the normal controls. These findings suggest that the intestinal obstruction in MMIHS is due to an abnormality of the smooth-muscle cells.

Interstitial cells of Cajal in the normal gut and in intestinal motility disorders of childhood

“…Several hypotheses have been proposed to explain the pathogenesis of MMIHS: genetic [173], neurogenic [172,175], myogenic [167,169,174] and hormonal origin [175,176]. Histological studies of the myenteric and submucosal plexuses of the bowel of MMIHS patients have revealed normal ganglion cells in the majority of the patients, decreased in some, hyperganglionosis and giant ganglia in others [168][169][170][171][172].…”

“…This syndrome is characterised by abdominal distension caused by a distended non-obstructed urinary bladder, microcolon, and decreased or absent intestinal peristalsis. Usually incomplete intestinal rotation and shortened small bowel are associated [167][168][169][170][171][172][173][174][175][176][177][178].…”

New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome)

“…Thinning of the intestinal longitudinal muscle layer and increased connective tissue proliferation between the intestinal smooth muscle layers have also been observed [7]. On electron microscopy, ‘central core' vacuolar degeneration in the center of smooth muscle cells has been described in smooth muscle cells in the bowel and bladder [7,9,10]. Immunohistochemical staining with antibodies against α-smooth muscle actin and caldesmon has shown markedly reduced staining in the longitudinal and circular layers of the small and large bowel and bladder [8,9,10].…”

“…On electron microscopy, ‘central core' vacuolar degeneration in the center of smooth muscle cells has been described in smooth muscle cells in the bowel and bladder [7,9,10]. Immunohistochemical staining with antibodies against α-smooth muscle actin and caldesmon has shown markedly reduced staining in the longitudinal and circular layers of the small and large bowel and bladder [8,9,10]. Recently familial [11,12,13] and de novo [13,14] ACTG2 mutations have been implicated in the etiology of familial visceral myopathy (FVM) as well as MMIHS.…”

Enteric nervous system and developmental abnormalities in childhood

“…Several subsequent reports have confirmed this [165,170,171]. Other investigators have reported absence or marked reduction in the a-smooth muscle actin and other contractile and cytoskeletal proteins in the smooth muscle layers of MMIHS bowel [165,171].…”