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American Family Physician Oct 2006Hirschsprung's disease (congenital megacolon) is caused by the failed migration of colonic ganglion cells during gestation. Varying lengths of the distal colon are... (Review)
Review
Hirschsprung's disease (congenital megacolon) is caused by the failed migration of colonic ganglion cells during gestation. Varying lengths of the distal colon are unable to relax, causing functional colonic obstruction. Hirschsprung's disease most commonly involves the rectosigmoid region of the colon but can affect the entire colon and, rarely, the small intestine. The disease usually presents in infancy, although some patients present with persistent, severe constipation later in life. Symptoms in infants include difficult bowel movements, poor feeding, poor weight gain, and progressive abdominal distention. Early diagnosis is important to prevent complications (e.g., enterocolitis, colonic rupture). A rectal suction biopsy can detect hypertrophic nerve trunks and the absence of ganglion cells in the colonic submucosa, confirming the diagnosis. Up to one third of patients develop Hirschsprung's-associated enterocolitis, a significant cause of mortality. Patients should be monitored closely for enterocolitis for years after surgical treatment of Hirschsprung's disease. With proper treatment, most patients will not have long-term adverse effects and can live normally.
Topics: Enterocolitis; Evidence-Based Medicine; Hirschsprung Disease; Humans; Infant, Newborn
PubMed: 17087425
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Nov 2020Hirschsprung's disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut... (Review)
Review
Hirschsprung's disease is a neurocristopathy, caused by defective migration, proliferation, differentiation and survival of neural crest cells, leading to gut aganglionosis. It usually manifests rapidly after birth, affecting 1 in 5000 live births around the globe. In recent decades, there has been a significant improvement in the understanding of its genetics and the association with other congenital anomalies, which share the pathomechanism of improper development of the neural crest. Apart from that, several cell populations which do not originate from the neural crest, but contribute to the development of Hirschsprung's disease, have also been described, namely mast cells and interstitial cells of Cajal. From the diagnostic perspective, researchers also focused on "Variants of Hirschsprung's disease", which can mimic the clinical signs of the disease, but are in fact different entities, with distinct prognosis and treatment approaches. The treatment of Hirschsprung's disease is usually surgical resection of the aganglionic part of the intestine, however, as many as 30-50% of patients experience persisting symptoms. Considering this fact, this review article also outlines future hopes and perspectives in Hirschsprung's disease management, which has the potential to benefit from the advancements in the fields of cell-based therapy and tissue engineering.
Topics: Hirschsprung Disease; Humans
PubMed: 33202966
DOI: 10.3390/medicina56110611 -
Orphanet Journal of Rare Diseases Jun 2020Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to... (Review)
Review
BACKGROUND
Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management.
AIMS
This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders.
METHODS
Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted.
RESULTS
Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion.
CONCLUSION
In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
Topics: Adult; Consensus; Europe; Hirschsprung Disease; Humans; Prevalence
PubMed: 32586397
DOI: 10.1186/s13023-020-01362-3 -
Translational Research : the Journal of... Jul 2013The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell... (Review)
Review
The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell population called the neural crest, a complete enteric nervous system is necessary for proper gut function. Disorders that arise as a consequence of defective neural crest cell development are termed neurocristopathies. One such disorder is Hirschsprung disease (HSCR), also known as congenital megacolon or intestinal aganglionosis. HSCR occurs in 1/5000 live births and typically presents with the inability to pass meconium, along with abdominal distension and discomfort that usually requires surgical resection of the aganglionic bowel. This disorder is characterized by a congenital absence of neurons in a portion of the intestinal tract, usually the distal colon, because of a disruption of normal neural crest cell migration, proliferation, differentiation, survival, and/or apoptosis. The inheritance of HSCR disease is complex, often non-Mendelian, and characterized by variable penetrance. Extensive research has identified a number of key genes that regulate neural crest cell development in the pathogenesis of HSCR including RET, GDNF, GFRα1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH. However, mutations in these genes account for only ∼50% of the known cases of HSCR. Thus, other genetic mutations and combinations of genetic mutations and modifiers likely contribute to the etiology and pathogenesis of HSCR. The aims of this review are to summarize the HSCR phenotype, diagnosis, and treatment options; to discuss the major genetic causes and the mechanisms by which they disrupt normal enteric neural crest cell development; and to explore new pathways that may contribute to HSCR pathogenesis.
Topics: Animals; Cell Movement; Enteric Nervous System; Gastrointestinal Tract; Hirschsprung Disease; Humans; Mutation; Neural Crest
PubMed: 23528997
DOI: 10.1016/j.trsl.2013.03.001 -
Archives of Pathology & Laboratory... May 2022Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has...
CONTEXT.—
Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has been established by histopathologic analysis of rectal biopsies. However, the criteria for the diagnosis have been questioned and modified, hindering diagnostic practice.
OBJECTIVE.—
To analyze the applicability of PTEN immunohistochemistry in the diagnosis of IND B and to compare with control cases and cases of Hirschsprung disease (HD).
DESIGN.—
PTEN immunohistochemical expression was analyzed in colorectal samples from 29 cases of IND B and compared with 4 control cases and 6 cases of HD. The pattern of PTEN immunoexpression was analyzed in glial cells of the submucosal and myenteric nerve plexuses and in neural fibrils of the muscularis propria using a scoring system.
RESULTS.—
Marked reduction or absence of PTEN expression was observed in glial cells of the submucosal nerve plexuses in all cases of the IND B group and in the myenteric nerve plexuses in 28 of 29 cases (96.5%). Lack of PTEN expression was detected in neural fibrils within the muscularis propria in 21 of 29 cases (72%) of the IND B group. PTEN expression was positive in the same neural structures of the control and HD groups.
CONCLUSIONS.—
PTEN immunohistochemistry may be a valuable tool in the diagnostic evaluation of IND B. Lack of or reduction of PTEN expression in neural fibrils within the muscularis propria suggests that involvement of the neuromuscular junction may be a key event in the pathogenesis of the motility disturbance occurring in IND B.
Topics: Humans; Immunohistochemistry; Enteric Nervous System; Myenteric Plexus; Hirschsprung Disease; Constipation; PTEN Phosphohydrolase
PubMed: 35943858
DOI: 10.5858/arpa.2021-0424-OA -
The EMBO Journal Jan 2023Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which...
Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype in vitro and in vivo. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short-chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of Bacteroides and Clostridium, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome-wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA-mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short-chain fatty acid metabolism-induced MEK1/2 signaling.
Topics: Rats; Animals; Fecal Microbiota Transplantation; Hirschsprung Disease; Signal Transduction; Fatty Acids, Volatile; Cell- and Tissue-Based Therapy
PubMed: 36382711
DOI: 10.15252/embj.2022111139 -
Archives of Disease in Childhood Jan 1996Current evidence on the pathogenesis of Hirschprung's disease, then, favours the 'abnormal microenvironment' hypothesis wherein the developing and migrating normal... (Review)
Review
Current evidence on the pathogenesis of Hirschprung's disease, then, favours the 'abnormal microenvironment' hypothesis wherein the developing and migrating normal neural crest cells confront a segmentally abnormal and hostile microenvironment in the colon. This hypothesis would account both for the congenital absence of ganglion cells in the wall of colon and also for the range of enteric neuronal abnormalities encountered including neuronal dysplasia, hypoganglionosis, and zonal aganglionosis. The abnormal constitution of the mesenchymal and basement membrane extracellular matrix in the affected segment of colon is presumably genetically determined and further understanding of the pathogenesis of this disorder will emerge as molecular geneticists characterise the specific genes and gene products associated with Hirschprung's disease. Advances in this field should permit gene probes to be developed to facilitate prenatal and postnatal diagnosis.
Topics: Enteric Nervous System; Extracellular Matrix Proteins; Hirschsprung Disease; Humans
PubMed: 8660047
DOI: 10.1136/adc.74.1.5 -
Digestive Diseases and Sciences Oct 2019Chronic megacolon is rarely encountered in clinical practice beyond infancy or early childhood. Most cases are sporadic, and some are familial megacolon and present... (Review)
Review
OBJECTIVE
Chronic megacolon is rarely encountered in clinical practice beyond infancy or early childhood. Most cases are sporadic, and some are familial megacolon and present during adolescence or adulthood. There is a need for diagnostic criteria and identifying genetic variants reported in non-Hirschsprung's megacolon.
METHODS
PubMed search was conducted using specific key words.
RESULTS
This article reviews the clinical manifestations, current diagnostic criteria, and intraluminal measurements of colonic compliance to confirm the diagnosis when the radiological imaging is not conclusive. Normal ranges of colonic compliance at 20, 30, and 44 mmHg distension are provided. The diverse genetic associations with chronic acquired megacolon beyond childhood are reviewed, including the potential association of SEMA3F gene in a family with megacolon.
CONCLUSIONS
Measuring colonic compliance could be standardized and simplified by measuring volume at 20, 30, and 44 mmHg distension to identify megacolon when radiology is inconclusive. Diverse genetic associations with chronic acquired megacolon beyond childhood have been identified.
Topics: Adolescent; Adult; Genetic Predisposition to Disease; Humans; Megacolon
PubMed: 30953226
DOI: 10.1007/s10620-019-05605-7 -
The Pan African Medical Journal 2013Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a...
Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Is a very rare congenital disorder with variable clinical expression. This report describes a 4-day-old male newborn with Waardenburg's syndrome associated with aganglionosis of the colon and terminal ileum, and review the relevant literature for draws attention to the causal relationship between these two entities.
Topics: Endothelins; Fatal Outcome; Hirschsprung Disease; Humans; Infant, Newborn; Male; Pigmentation Disorders; Waardenburg Syndrome
PubMed: 23565307
DOI: 10.11604/pamj.2013.14.60.1543 -
BMC Gastroenterology Jan 2018Acquired Megacolon (AMC) is a condition involving persistent dilatation and lengthening of the colon in the absence of organic disease. Diagnosis depends on subjective... (Review)
Review
BACKGROUND
Acquired Megacolon (AMC) is a condition involving persistent dilatation and lengthening of the colon in the absence of organic disease. Diagnosis depends on subjective radiological, endoscopic or surgical findings in the context of a suggestive clinical presentation. This review sets out to investigate diagnostic criteria of AMC.
METHODS
The literature was searched using the databases - PubMed, Medline via OvidSP, ClinicalKey, Informit and the Cochrane Library. Primary studies, published in English, with more than three patients were critically appraised based on study design, methodology and sample size. Exclusion criteria were studies with the following features: post-operative; megarectum-predominant; paediatric; organic megacolon; non-human; and failure to exclude organic causes.
RESULTS
A review of 23 articles found constipation, abdominal pain, distension and gas distress were predominant symptoms. All ages and both sexes were affected, however, symptoms varied with age. Changes in anorectal manometry, histology and colonic transit are consistently reported. Studies involved varying patient numbers, demographics and data acquisition methods.
CONCLUSIONS
Outcome data investigating the diagnosis of AMC must be interpreted in light of the limitations of the low-level evidence studies published to date. Proposed diagnostic criteria include: (1) the exclusion of organic disease; (2) a radiological sigmoid diameter of ~ 10 cm; (3) and constipation, distension, abdominal pain and/or gas distress. A proportion of patients with AMC may be currently misdiagnosed as having functional gastrointestinal disorders. Our conclusions are inevitably tentative, but will hopefully stimulate further research on this enigmatic condition.
Topics: Abdominal Pain; Colonography, Computed Tomographic; Colonoscopy; Constipation; Gases; Gastrointestinal Transit; Humans; Intestines; Manometry; Megacolon
PubMed: 29385992
DOI: 10.1186/s12876-018-0753-7