Hirschsprung's Disease and Idiopathic Megacolon*1

Bodian, Martin; Stephens, F. Douglas; Ward, Beverley

doi:10.1016/s0140-6736(49)90340-2

Cited by 212 publications

(58 citation statements)

References 2 publications

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“…In 1886, Harald Hirschsprung reported two infants with the disorder that now bears his name (9,10). The link between distal bowel aganglionosis and the massive proximal bowel distension that occurs with HSCR was not understood, however, until the pioneering studies of Swenson and Bill, Swenson et al, Bodian et al, Zuelzer and Wilson, and Whitehouse and Kernohan in 1948 and 1949, which showed that the absence of enteric neurons causes tonic contraction and functional obstruction (11)(12)(13)(14)(15). HSCR in a child with Down syndrome was first reported in 1956 (16), and increased occurrence of HSCR in individuals with Down syndrome was recognized in 1963 (17), suggesting that one or more genes on chromosome 21 contributes to HSCR etiology.…”

Section: Hirschsprung's Disease: Congenital Absence Of Distal Bowel Ementioning

confidence: 99%

Hirschsprung’s disease, Down syndrome, and missing heritability: too much collagen slows migration

Heuckeroth¹

2015

Journal of Clinical Investigation

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C o m m e n t a r y4 3 (17), suggesting that one or more genes on chromosome 21 contributes to HSCR etiology. Up to 10% of children with HSCR have Down syndrome, and 1% to 2% of children with Down syndrome have HSCR. Thus, Down syndrome increases HSCR risk about 50-to 100-fold above the general population risk (~1:5,000) and is a common underlying partially penetrant cause of HSCR (4).Over the past few decades there have been dramatic advances in our understanding of HSCR anatomy, embryology, physiology, and genetics (4,5,18). Early studies by Yntema and Hammond showed that the ENS forms from enteric neural crestderived cells (ENCDCs) that originate primarily in the vagal region of the neural tube (19). These ENCDCs proliferate vigorously as they colonize fetal bowel in a rostral to caudal progression, pursuing one of the longest migratory routes of any cell population during fetal development ( Figure 1A). ENCDCs then differentiate into diverse neuron and glia subtypes that form a network in the bowel wall with about as many neurons as the spinal cord and every transmitter in the central nervous system (3, 18). Despite these advances in our understanding of ENS development, the causal link between trisomy 21 and increased HSCR incidence has remained elusive. Analysis of partial trisomy 21 phenotypes suggested that an extra copy of at least one gene in the interval from 33.5 to 46.25 Mb increased HSCR risk (20). This interval contains 122 known genes, including DSCAM, BACE2, COL18A1, and COL6A1. A recent SNP association study suggested that excess DSCAM may be important for HSCR pathogenesis in Down syndrome, but excess DSCAM has not been confirmed experimentally to cause HSCR-like disease in model systems (21). Unbiased approach to identify genes critical for ENS developmentIn this issue, Soret and colleagues took an unbiased, forward genetics approach and used insertional mutagenesis to identify potential regulators of neural crest-derived cell (NCC) migration (22). To simplify the screening process, Soret et al. randomly inserted a tyrosinase (Tyr) minigene, which rescues pigment production in NCCderived melanocytes, into albino FVB/N mice and then evaluated animals with nonuniform pigment patterns. Because melanocytes and the ENS are both neural crest derivatives, some mice with pigmentation defects were also expected to have ENS defects, mimicking the human "neurocristopathy" called Waardenburg-Shah syndrome (Waardenburg syndrome type Hirschsprung's disease (HSCR) causes functional intestinal obstruction due to the absence of the enteric nervous system (ENS) in the distal bowel and is usually diagnosed shortly after birth or during childhood. While several genetic and nongenetic factors have been linked to HSCR, the underlying mechanisms that prevent ENS precursors from colonizing distal bowel during fetal development are not completely understood in many affected children. In this issue of the JCI, Soret and colleagues identify a new mechanism that causes HSCR-like disease in mice and involves deposition o...

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Section: Hirschsprung's Disease: Congenital Absence Of Distal Bowel Ementioning

confidence: 99%

Hirschsprung’s disease, Down syndrome, and missing heritability: too much collagen slows migration

Heuckeroth¹

2015

Journal of Clinical Investigation

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“…Primary GINMDs include oesophageal achalasia (Hertz 1915), gastroparesis (Shellito et al 1984), enteric dysmotility (ED) (Wingate et al 2002) and chronic idiopathic intestinal pseudo-obstruction (CIPO) (Dudley et al 1958) (for the purposes of this thesis ED and CIPO are referred to collectively as severe intestinal dysmotility: SID), slow-transit constipation (STC) (Preston et al 1986) and idiopathic megabowel (Bodian et al 1949)..…”

Section: Gastrointestinal Neuromuscular Diseasesmentioning

confidence: 99%

“…Idiopathic megacolon describes a group of patients with intractable constipation associated with rectal or colonic dilatation in the absence of mechanical obstruction or evident cause (Bodian et al 1949). Several pathological abnormalities of nerve, ICC and smooth muscle have been reported including immune-mediated myenteric ganglionitis associated with neuronal degeneration (De Giorgio et al 2002).…”

Section: Idiopathic Megacolonmentioning

confidence: 99%

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Hubball

Martin

Lang

et al. 2009

Progress in Neurobiology

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Dysfunction of the gastrointestinal neuromuscular apparatus (including interstitial cells ofCajal) is presumed to underlie a heterogeneous group of disorders collectively termed gastrointestinal neuromuscular diseases (GINMDs). Humoral (antibody)-mediated autoimmunity directed against ligand-or voltage-gated ion channels or associated proteins involved in neuromuscular transmission is associated with several acquired neuromuscular diseases of the periphery and is now implicated in an increasing number of less well-characterised diseases. Anti-channel antibodies have been reported in small numbers of patients with GINMD, particularly in those with GI dysfunction secondary to an underlying disease such as neoplasia or infection. However, little is known of humoral autoimmunity in primary GINMDs.This thesis investigated the association between anti-channel antibodies and GINMD, and the human GI tract as a potential target of anti-channel antibodies. The presence of antivoltage-and ligand-gated antibodies was investigated in the serum of patients with primary achalasia, enteric dysmotility and intestinal pseudo-obstruction, and in those with GINMD secondary to Chagas' disease. The functional effect of sera from some of these patients on colonic smooth muscle contractility was also characterised. Finally, the distribution of six voltage-gated potassium channels (VGKCs), which serve essential roles in the peripheral and central nervous systems and are known targets of pathological autoantibodies, were investigated in all layers of the human GI tract.Our findings suggest that currently recognised anti-channel antibodies are not a common pathogenic factor in primary GINMDs. Anti-channel antibodies, in particular anti-VGKC antibodies, were however found in a significant number of individuals with Chagas' disease. Furthermore, circulating factors in patients with chagasic GI disease altered GI smooth muscle contractility in vitro which may have pathological relevance to GI

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“…In the classical anomaly of the ENS, Hirschsprung's disease (incidence 1 in 5,000 newborns), enteric neurons are absent in the most distal part of the colon [ Whitehouse and Kernohan, 1948;Bodian et al, 1949;Spouge and Baird, 1985]. In infancy, especially in the first year of life, inability to pass feces, fol lowed by abdominal distension and bilious vomiting leads to life-threatening situations.…”

Section: Use Of Mabs In the Diagnosis Of Anomalies Of The Ensmentioning

confidence: 99%

Monoclonal Antibodies for Diagnosis and Research in Enteric Nervous System Pathology

Tibboel

Meijers²,

Klück³

et al. 1987

Dev Neurosci

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Monoclonal antibodies (MAb) directed against neuron-specific epitopes are valuable tools in the diagnosis of congenital and acquired enteric nervous system anomalies. MAb raised against cytoskeleton proteins (neurofilaments) revealed a characteristic staining pattern in patients with various motility disorders of the gut. Application of MAb in the study of the development of the enteric nervous system in the chicken embryo provided new insights into the fate of migrating neural crest cells. The relationship between mesenchymal target cells in the gut and proliferating neural crest cells was studied by means of MAb raised against cell surface markers (HNK-1) in combination with characterization of the microenvironment using monoclonal antibodies raised against cell adhesion molecules (N-CAM).

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Hirschsprung's Disease and Idiopathic Megacolon*1

Cited by 212 publications

References 2 publications

Hirschsprung’s disease, Down syndrome, and missing heritability: too much collagen slows migration

Hirschsprung’s disease, Down syndrome, and missing heritability: too much collagen slows migration

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

Monoclonal Antibodies for Diagnosis and Research in Enteric Nervous System Pathology

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