Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021843 (bowel obstruction)
 9,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six children aged from 1 day to 15 years (18 boys and 8 girls) with visceral neuropathies are analyzed. Clinical symptomatology is dominated by abdominal distension, attacks of occlusion, abdominal pain, and malnutrition. Intestine bacterial overgrowth is frequent. From aspiration biopsies, surgical rectal biopsies, and, in some cases, ileal or ileocolic biopsies, histopathological studies revealed two patterns. One group had abnormalities of the myenteric plexus identified by conventional light microscopic studies, with two patterns: [myenteric plexus hyperplasia (9 patients), characterized by large ganglionic nodes, penetration into the mucosal zone, and altered argyrophilic neurons]. Clinically this pattern was observed in four patients with multiple endocrine neoplasia syndrome with risk of medullary thyroid carcinoma. The second pattern observed was characterized by glial cell hyperplasia (15 patients). Ganglion cells are present but are small and sparse, often infiltrated by collagen tissue; Schwann nerve fibers are hypertrophic. Eleven patients presented with neonatal intestinal obstruction. The second group is characterized by normal conventional light microscopic examination, but silver stains revealed important abnormalities of argyrophobic cells (one case) or argyrophilic cells (one case). In the two groups, most of the patients needed intestinal derivation and prolonged nutritional support with total parenteral nutrition.
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PMID:Visceral neuropathies responsible for chronic intestinal pseudo-obstruction syndrome in pediatric practice: analysis of 26 cases. 239 57

A series of 21 patients with NID is presented. A histologic and histochemical picture of NID was seen in an heterogenous group of patients. NID was associated with bowel obstruction and/or perforation in six neonates and infants. One neonate died. During follow-up the bowel histology gradually normalized in four of the five patients. NID was found incidentally in four patients with anorectal malformations and two with Hirschsprung's disease. Three patients with Hirschsprung's disease and associated NID had chronic proctitis; one patient with an anorectal anomaly had chronic obstipation and megacolon and one proctitis. Two children with multiple endocrine neoplasia 2b syndrome and chronic obstipation had typical NID in their rectum biopsies, as did a 50-year-old woman with CIIP. The clinical heterogeneity of patients with NID suggests that NID may not be a distinct clinical entity but rather a reaction of the neuronal network of the bowel wall and could be caused either by congenital or secondary factors.
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PMID:Neuronal intestinal dysplasia. 251 3

The diagnosis and management of patients with multiple endocrine neoplasia (MEN) type IIA and type IIB are of special challenge to pediatric surgeons. Patients characteristically present early in life with significant intestinal symptoms at a time when the characteristic phenotypic features of MEN IIB are frequently absent. We are reporting 12 patients with MEN type II (9 with type IIA and 3 type IIB or Sipple's syndrome), all of whom presented with gastrointestinal manifestations. All 12 patients had signs and symptoms of bowel obstruction during the neonatal period. An unusual association of Hirschsprung's disease and MEN IIA was noted in our nine patients found among a kindred of 92 individuals. All three patients with Sipple's syndrome (MEN IIB) had severe gastrointestinal symptoms since birth, including recurrent pseudoobstruction. The possibility of MEN type II should be considered in all cases of bowel obstruction in the newborn period. Screening for medullary carcinoma of the thyroid must be carried out from infancy. A detailed family history is very important to avoid unnecessary surgery for bowel obstruction in Sipple's syndrome.
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PMID:Gastrointestinal manifestations of Sipple syndrome in children. 288 44

Multiple Endocrine Neoplasia type 2b (MEN 2b) is a rare syndrome. The principal features are: medullary thyroid carcinoma (MTC), dysmorphism, a ganglioneuromatosis and pheochromocytomas. Eight cases of MEN 2b have been observed at the Institute Gustave Roussy, between 1968 and 1983. Seven involved children under 15 years of age. Eight had a bilateral MTC; six had dysmorphism; six had mucosal tongue neuromas. Six were troubled with visceral ganglioneuromatosis of whom two had intestinal obstruction and one urinary chronic retention. One patient had pheochromocytoma with hypertension. From this experience and other data it appears that: the dysmorphism is frequently poorly interpreted; the visceral ganglioneuromatosis is an early and severe feature; it is important to examine the patient for pheochromocytoma; the MTC must be detected by calcitonin dosage after stimulation, and requires total thyroidectomy; familial screening must be done. To improve the poor prognosis of MEN 2b, early diagnosis and aggressive treatment are necessary.
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PMID:[Multiple endocrine neoplasia type 2b. Clinical, diagnostic and therapeutic aspects]. 614 75

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most common cause of congenital bowel obstruction with an incidence of 1 in 5000 live births. Recently, linkage of an incompletely penetrant, dominant form of HSCR was reported, followed by identification of mutations in the RET receptor tyrosine kinase. To determine the frequency of RET mutations in HSCR and correlate genotype with phenotype, we have screened for mutations among 80 HSCR probands representing a wide range of phenotypes and family structures. Polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis of RET's 20 exons for mutations among probands revealed eight putative mutations (10%). Sequence changes, which included missense, frameshift and complex mutations, were detected in both familial and isolated cases, among patients with both long- and short-segment HSCR and in three kindreds with other phenotypes (maternal deafness, talipes and malrotation of the gut, respectively). Two mutations (C609Y and C620R) we identified have previously been associated with multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC) and, on rare occasions, HSCR. Thus, while HSCR family members may be at risk for developing neuroendocrine tumors, it follows that identical mutations in RET may be able to participate in the pathogenesis of distinct phenotypes. Our data suggest that: (i) the overall frequency of RET mutations in HSCR patients is low and therefore, other genetic and/or environmental determinants contribute to the majority of HSCR susceptibility, and (ii) at present, there is no obvious relationship between RET genotype and HSCR phenotype.
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PMID:Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. 763 41

Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2. No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report on nonsense and missense mutations in the extracellular domain of the RET protein (exons 2, 3, 5 and 6) in 6 unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A.
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PMID:[Mutations of RET proto-oncogene in Hirschsprung disease]. 800 Sep 15

Hirschsprung's disease is a genetic disorder of neural crest development affecting 1 in 5,000 births. It is characterized by the absence of intramural ganglion cells in the hindgut, which often results in partial to complete intestinal obstruction during the first years of life. An autosomal dominant gene causing this disease was recently mapped to chromosome 10q11.2 (refs 1,2), using an interstitial deletion of this region isolated in a cell hybrid. It was subsequently localized to a 250-kilobase interval which contains the RET proto-oncogene. Using flanking intronic sequences as primers to amplify 12 of the 20 exons of RET from genomic DNA of 27 Hirschsprung's disease patients, we have now identified four mutations (one frameshift and three missense) that totally disrupt or partially change the structure of the tyrosine kinase domain of the RET protein (Ret). Mutations in the extracellular cysteine-rich domain of Ret have been identified previously in patients with multiple endocrine neoplasia type 2A, and a targeted mutation in the tyrosine kinase domain of the same gene produces intestinal aganglionosis and kidney agenesis in homozygous transgenic mice. Our results support the hypothesis that RET, in addition to its potential role in tumorigenesis, plays a critical role in the embryogenesis of the mammalian enteric nervous system.
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PMID:Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. 790 65

Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2 (refs 6, 7). No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report nonsense and missense mutations in the extracellular domain of RET protein (exons 2, 3, 5 and 6) in six unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A.
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PMID:Mutations of the RET proto-oncogene in Hirschsprung's disease. 790 65

Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial-cell-line-derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two 'faces' of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect.
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PMID:RET in human development and oncogenesis. 917 4

Multiple endocrine neoplasia type 2 (MEN2) and Hirschsprung's disease (HSCR) are two dominantly inherited neurocristopathies ascribed to mutations in the RET gene [Chakravarti, 1996; Pasini et al., 1996; Eng and Mulligan, 1997]. MEN2 is a cancer syndrome comprising three related clinical subtypes: (1) MEN type 2A (MEN2A; MIM# 171400) characterized by the association of medullary thyroid carcinoma (MTC), pheochromocytoma (Pheo), and hyperparathyroidism; (2) MEN type 2B (MEN2B; MIM# 162300), which includes MTC, Pheo, mucosal neuromas, ganglioneuromatosis of the digestive tract, and skeletal abnormalities; and (3) familial MTC (FMTC; MIM# 155240), defined by the sole occurrence of MTC. HSCR (MIM# 142623) is a congenital malformation caused by the absence of enteric plexuses in the hindgut, leading to bowel obstruction in neonates. The RET gene (MIM# 164761) codes for a transmembrane tyrosine kinase, a component of a multimeric complex that also comprises one of four members of a novel family of glycosylphosphatidylinositol (GPI)-anchored receptor, GFRalpha((1-4) (e.g., GFRA1, MIM# 601496; references are detailed in Baloh et al. [1998]. Four structurally related soluble factors-glial cell line-derived neurotrophic factor (GDNF), neurturin, persephin, and artemin-are the ligands of these multimolecular receptors in which the nature of the GFRalpha determines the ligand specificity of the complex [see Baloh et al., 1998, for references]. It is well documented that RET/GFRalpha-1/GDNF delivers a signal critical for the survival of the early neural crest-derived precursors that colonize the intestine below the rostral foregut and give rise to the enteric nervous plexuses [Gershon, 1997; Cacalano et al., 1998; Enomoto et al., 1998].
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PMID:Co-segregation of MEN2 and Hirschsprung's disease: the same mutation of RET with both gain and loss-of-function? 1022 Jan 48


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