-
American Journal of Physiology.... Jun 2021Visceral 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... (Review)
Review
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.
Topics: Cytoskeleton; Humans; Intestinal Pseudo-Obstruction; Muscle, Smooth; Mutation
PubMed: 33729000
DOI: 10.1152/ajpgi.00066.2021 -
Taiwanese Journal of Obstetrics &... Jan 2024Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive... (Review)
Review
Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive uropathy, prune belly syndrome, cloacal anomalies, limb-body wall complex, amniotic band syndrome, anorectal malformations, VACTERL association (vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies and limb abnormalities) and fetal overgrowth syndrome such as Bechwith-Wiedemann syndrome and Sotos syndrome. This review provides an overview of chromosomal abnormalities associated with fetal megacystis which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal megacystis.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Diabetes, Gestational; Fetal Macrosomia; Abnormalities, Multiple; Chromosome Aberrations; Urinary Bladder; Duodenum; Fetal Diseases
PubMed: 38216262
DOI: 10.1016/j.tjog.2023.11.006 -
Radiology Case Reports 2007We report a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a newborn female infant who presented with an abdominal mass, absent bowel...
We report a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a newborn female infant who presented with an abdominal mass, absent bowel sounds, and feeding intolerance with bilious emesis. MMIHS is a rare congenital bowel and bladder defect requiring surgery and chronic total parenteral nutrition in an attempt to sustain life. With few exceptions, it is predominately fatal within the first six months of life. We describe the relevant clinical and radiologic findings with ultrasound correlation of this case followed by a brief review of literature included in the discussion.
PubMed: 27303483
DOI: 10.2484/rcr.2007.v2i4.26 -
Clinics in Colon and Rectal Surgery Jan 2022Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small... (Review)
Review
Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small molecules, a subset of medically refractory patients still requires colectomy. Recent population-based studies demonstrate a trend toward a decrease in the rates of surgery for UC patients in the biological era, although the potential of disease modification with these agents is still debated. As the concept of irreversible bowel damage is underexplored in UC, refractory patients can be exposed to multiple treatments losing optimal timing for surgery and further developing complications such as dysplasia/cancer, dysmotility, microcolon, and other functional abnormalities. This review aims to discuss the concept of disease progression in UC, explore the limitations of medical treatment in refractory UC patients, and propose the application of a three-step algorithm that allows timely indication for surgery in clinical practice.
PubMed: 35069028
DOI: 10.1055/s-0041-1740036 -
Pediatric Surgery International Apr 2023Interstitial cells of Cajal (ICCs) are pacemaker cells of gastrointestinal motility that generate and transmit electrical slow waves to smooth muscle cells in the gut... (Review)
Review
Interstitial cells of Cajal (ICCs) are pacemaker cells of gastrointestinal motility that generate and transmit electrical slow waves to smooth muscle cells in the gut wall, thus inducing phasic contractions and coordinated peristalsis. Traditionally, tyrosine-protein kinase Kit (c-kit), also known as CD117 or mast/stem cell growth factor receptor, has been used as the primary marker of ICCs in pathology specimens. More recently, the Ca-activated chloride channel, anoctamin-1, has been introduced as a more specific marker of ICCs. Over the years, various gastrointestinal motility disorders have been described in infants and young children in which symptoms of functional bowel obstruction arise from ICC-related neuromuscular dysfunction of the colon and rectum. The current article provides a comprehensive overview of the embryonic origin, distribution, and functions of ICCs, while also illustrating the absence or deficiency of ICCs in pediatric patients with Hirschsprung disease intestinal neuronal dysplasia, isolated hypoganglionosis, internal anal sphincter achalasia, and congenital smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome.
Topics: Infant; Child; Humans; Child, Preschool; Interstitial Cells of Cajal; Clinical Relevance; Hirschsprung Disease; Gastrointestinal Motility; Anal Canal; Proto-Oncogene Proteins c-kit
PubMed: 37101012
DOI: 10.1007/s00383-023-05467-1 -
Journal of Pediatric Gastroenterology... May 2022The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms...
BACKGROUND AND AIMS
The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease.
METHODS
Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored.
RESULTS
One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores.
CONCLUSIONS
Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.
Topics: Abnormalities, Multiple; Actins; Colon; Female; Humans; Intestinal Pseudo-Obstruction; Male; Phenotype; Pregnancy; Urinary Bladder
PubMed: 35149643
DOI: 10.1097/MPG.0000000000003400 -
JPGN Reports Nov 2022Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous condition characterized by impaired gastrointestinal propulsion, a broad clinical spectrum, and...
UNLABELLED
Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous condition characterized by impaired gastrointestinal propulsion, a broad clinical spectrum, and variable severity. Several molecular bases underlying primary PIPO have been identified, of which autosomal dominant ACTG2-related visceral myopathy is the most common in both familial or sporadic primary PIPO cases. We present a family with autosomal recessive ACTG2-related disease in which both parents have mild gastrointestinal symptoms and sons have severe PIPO and bladder dysfunction.
METHODS
Clinical genome sequencing was performed on the patients and the mother. Immunohistochemistry was performed on intestinal tissue from the patients to show expression levels of the .
RESULTS
Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the gene and a maternally inherited missense variant p.Val10Met in the gene.
DISCUSSION
This case demonstrates that monoallelic hypomorphic variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding exon can be an under-recognized cause of mild gastrointestinal symptoms unidentifiable by exome sequencing, explaining some instances of interfamilial variability with an apparent autosomal dominant inheritance. Genome sequencing is recommended as a genetic work-up for primary or idiopathic PIPO because of genetic heterogeneity.
PubMed: 37168481
DOI: 10.1097/PG9.0000000000000258 -
Journal of Pediatric Gastroenterology... Apr 2021Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients.
OBJECTIVES
Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients.
METHODS
We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years.
RESULTS
We identified 25 patients with MMIHS (68% girls, 13 transplanted). One transplanted and 1 nontransplanted patient were lost to follow-up. We estimated 100, 100, and 86% for 5-, 10-, and 20-year survival, respectively, with only 1 death. Of the 22 patients alive at the time of study (11 transplanted, 11 nontransplanted), median age was 9.2 years (range 2.7-22.9 years). Longest posttransplant follow-up was 16 years. Seventeen patients had available prenatal imaging reports; all showed distended bladder. Eight had genetic testing (5, ACTG2; 2, MYH11; 1, MYL9). Almost all patients had normal growth with median weight z-score -0.77 (interquartile range -1.39 to 0.26), height z score -1.2 (-2.04 to -0.48) and body mass index z-score 0.23 (-0.37 to 0.93) with no statistical difference between transplanted and nontransplanted patients. All nontransplanted patients were on parenteral nutrition with minimal/no feeds, and all except 1 of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin, and creatinine fell within the reference ranges.
CONCLUSIONS
This is the largest single-center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Child, Preschool; Colon; Female; Follow-Up Studies; Humans; Intestinal Pseudo-Obstruction; Male; Peristalsis; Pregnancy; Retrospective Studies; Urinary Bladder; Young Adult
PubMed: 33264186
DOI: 10.1097/MPG.0000000000003008