Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS): Series of 4 Cases Caused by Mutation of ACTG2 (Actin Gamma 2, Smooth Muscle) Gene

Abstract

MMIHS, also known as Berdon’s syndrome, is a rare disease that belongs to primary causes of CIPOS (chronic intestinal pseudoobstruction syndrome). Clinical characteristics of MMIHS are differential, but we come across the following classic symptoms: disorders of intestinal peristalsis, microcolon, and megacystis. In this article, we present a series of 4 patients with Berdon’s syndrome, in whom we managed to identify the genetic causes of MMIHS. All infants showed clinical features of bowel obstruction and dysfunction of the urinary system after birth. Two of them also manifested disorders from other systems. The prognosis for these patients is poor, but a constant betterment of management in MMIHS, in which the leading role plays TPN (total parental nutrition), causes improvement of patients’ survival.

Intestinal Pathology in Patients With Pathogenic ACTG2-Variant Visceral Myopathy: 16 Patients From 12 Families and Review of the Literature

“…The cohort included patients from 12 families: 10 unrelated patients, 1 pair of siblings (patients 6 and 7), and an affected father (patient 8) and his 3 affected children (patients [9][10][11]. For every proband (first affected family member), histopathological evaluation had preceded molecular genetic studies.…”

“…Some investigators specifically noted an absence of histological abnormalities. [3][4][5][6][7] Others reported a variety of other putative alterations in the muscularis propria including thinning of one or both muscle layers, [8][9][10] "vacuolar change", 7,9,11 intestinal neuronal dysplasia type B, 12 aplastic desmosis, 12 "disorderly arranged intramyenteric neural tissue", 13 nuclear palisading, 9 haphazard arrangement of smooth muscle cells, 13,14 muscle degeneration and fibrosis, 15 intracellular inclusion bodies, 16,17 and cytoplasmic aggregates or clumps of ACTG2-immunoreactive material. 10,16 These divergent findings prompted us to conduct a light and electron microscopic and immunohistochemical study of intestinal specimens from a series of 16 patients with pathogenic ACTG2 variants, in an effort to identify potentially distinctive features for patients with this form of visceral myopathy.…”

Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome: A Case Report of an Uncommon Condition

“…Different autosomal dominant and recessive genetic mutations associated with this syndrome have been described; however, in up to 50% of patients, the underlying alteration cannot be identified [2,13]. The mutation in the ACTG2 gene is the most frequent (88% of cases); it shows autosomal dominant inheritance and it generates the most severe phenotype.…”

“…The megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) or Berdon syndrome is a rare condition, first described in 1976, with 450 reported cases in the literature up to 2019 [1,2]. It is part of the spectrum of intestinal myopathies, with Hirschsprung's disease being the most common [3].…”

“…Most patients are diagnosed after birth, but prenatal diagnosis is possible in up to 25% of cases based on ultrasound findings [4,8]. Imaging studies are essential for diagnosis, but genetic testing is necessary to detect underlying mutations that may influence prognosis and family counseling [2].…”