1/13. Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.OBJECTIVE: The RET proto-oncogene is known to be the susceptibility gene for various disease phenotypes, including multiple endocrine neoplasia type 2 (men 2). Recent studies have also suggested an involvement of RET in the development of the mammalian kidney. Although kidney agenesis or dysgenesis has been observed in mice lacking functional ret, no clinically relevant kidney abnormalities have been reported in individuals with known RET mutations and familial medullary thyroid carcinoma (FMTC). We have studied a family with five members affected with isolated FMTC. dna analysis was performed and the involved RET mutation was identified. Amongst these patients were a woman and her son. DESIGN: Case report. SETTING: University department. patients: A 32-year-old woman and her son with FMTC and unilateral renal agenesis. RESULTS: The woman's abdominal ultrasound findings demonstrated unilateral renal absence of the left kidney. Her son, when only a few months old, had undergone surgical treatment for Hirschsprung's disease. Abdominal ultrasonography was performed recently, and left-side renal absence was diagnosed. Intravenous pyelography confirmed the agenesis of his left kidney, whilst the contralateral kidney displayed compensatory hypertrophy. CONCLUSIONS: The involvement of the RET proto-oncogene in the early growth and differentiation of the human kidney is now generally accepted. We believe that at least a proportion of patients with men 2 may have undiagnosed renal malformations. We suggest therefore that noninvasive imaging techniques, such as ultrasonography, should be used to explore the presence of renal abnormalities in subjects with demonstrated RET mutations.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
2/13. RET mutation profile and variable clinical manifestations in a family with multiple endocrine neoplasia type 2a and Hirschsprung's disease.BACKGROUND: RET proto-oncogene germ line mutations are associated with the inherited multiple endocrine neoplasia type 2 syndromes (men 2), as well as with familial and sporadic Hirschsprung's disease (HSCR). In this study, we report a family in which the men 2A and the HSCR phenotypes are associated with a single point mutation in exon 10 of the RET proto-oncogene. Furthermore, we have investigated polymorphic sequence variants of the RET proto-oncogene. methods: family members were tested for RET proto-oncogene mutations in exons 10, 11, 13, 14, 15, and 16 by double-gradient denaturing-gradient gel electrophoresis, nucleotide sequence analysis, and restriction endonuclease digestion of polymerase chain reaction products. The status of exon 2 and 13 polymorphic sites was investigated by EagI and TaqI digestion in 12 selected patients. RESULTS: A heterozygous C618R mutation of RET exon 10 was identified in 12 family members. Five out of 7 children with mildly elevated pentagastrin-stimulated calcitonin levels who carried the mutation underwent prophylactic thyroidectomy before the age of 12. C-cell hyperplasia (CCH) was found in 4 children and a microscopic medullary thyroid carcinoma (MTC) in an 8-year-old female. Neither CCH nor MTC was found in the only family member affected with HSCR, an 8-year-old male. This patient inherited the mutated RET allele from his mother, who had MTC but not HSCR, together with a rare allelic variant at codon 45 of RET exon 2. CONCLUSIONS: This report of a newly-described kindred with the infrequent clinical association between men 2A and HSCR confirms the risk of the latter phenotype among carriers of RET exon 10 cysteine codon mutations. Nevertheless, the influence of other genetic or environmental factors cannot be excluded.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
3/13. Cys611Ser mutation in RET proto-oncogene in a kindred with medullary thyroid carcinoma and Hirschsprung's disease.Germline mutations in the RET proto-oncogene are responsible for the development of human hereditary diseases, including multiple endocrine neoplasia (men) type 2A and 2B, familial medullary thyroid carcinoma (FMTC), and Hirschsprung's disease (HSCR). It has been reported that some families developed both men 2A/FMTC and HSCR, in which a mutation in a cysteine residue at codon 609, 618, or 620 in the RET gene was present. Here we report a novel RET mutation detected in a Japanese family with medullary thyroid carcinoma and HSCR. A germline mutation in cysteine 611 of the RET gene was identified in this family, which introduced an amino-acid change from cysteine to serine. By biological and biochemical analyses of mutant RET proteins, we previously predicted the potentiality that amino-acid substitution for cysteine 611 as well as cysteines 609, 618, and 620 would promote the development of men 2A/FMTC and HSCR. This clinical case substantiates our suggestion for the mechanism of the development of both the diseases.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
4/13. The combination of Hirschsprung's disease and achalasia.The unusual combination of Hirschsprung's disease and Achalasia in one case treated by standard procedures led to the discussion about RET germ-line mutations and consequently to the speculation about higher risk for multiple endocrine neoplasia syndrome type 2-related tumors. Although a mutation could be excluded by sequence analysis in this case, the correlation of these specific diseases affords additive investigations to make sure that no further prophylactic procedures were necessary.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
5/13. Multiple endocrine neoplasia 2B presenting with pseudo-Hirschsprung's disease.multiple endocrine neoplasia type 2b (men 2B) is a rare syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and typical phenotypic features, such as marfanoid habitus, multiple mucosal ganglioneuromas and thickened corneal nerves. Individuals with men 2B may develop megacolon and pseudo-obstruction due to intestinal ganglioneuromatosis simulating Hirschsprung's (HSCR) disease. We hereby describe the clinical and genetic features of a 21-year-old male patient with men 2B associated with pseudo-HSCR disease. The patient had MTC, pheochromocytoma, marfanoid habitus, multiple mucosal ganglioneuromas, thickened corneal nerves and severe gastrointestinal involvement. Emergent laparotomy was performed when he was presented with acute bowel obstruction. The myenteric and submucosal nerve plexuses in the small and large intestines were composed of diffusely hyperplasic, disorganized, mature ganglion cells. genetic testing revealed a de novo ret proto-oncogene germline mutation in codon 918 in exon 16. megacolon and pseudo-obstruction similar to the HSCR disease may develop in patients with men 2B. However, the observed dysmotility is the result of an abnormal proliferation of intramural ganglion cells in contrast to the absence of enteric ganglia which were present in the HSCR disease. Attentiveness about the phenotypic characteristics and unusual findings might lead to early and correct diagnosis of the men 2B syndrome. This approach improves the survival rate and quality of life considerably.- - - - - - - - - - ranking = 1keywords = endocrine (Clic here for more details about this article) |
6/13. Multiple endocrine neoplasia type II B with symptoms suggesting Hirschsprung's disease: a case report.A 3-year-old child was referred with a tentative diagnosis of Hirschsprung's disease because of life-long constipation and "megacolon" demonstrated radiographically. Our rectal biopsy revealed hyperganglionosis suggestive of multiple endocrine neoplasia (men) type II B. This, in addition to an elevated serum calcitonin level, prompted surgical removal of her thyroid, which appeared grossly normal but on sectioning, contained a medullary carcinoma in each lobe. She remains disease-free 5 years later. Gastrointestinal symptoms are a significant component of the men type II B syndrome, and often antedate the full phenotypic expression of the syndrome and the development of potentially lethal endocrine neoplasms. On the basis of this experience, it is recommended that men II B be included in the differential diagnosis of chronic constipation.- - - - - - - - - - ranking = 1.2keywords = endocrine (Clic here for more details about this article) |
7/13. Gastrointestinal manifestations of Sipple syndrome in children.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.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
8/13. Hypothalamic-pituitary dysfunction and Hirschsprung's disease in the bardet-biedl syndrome.A child with the bardet-biedl syndrome associated with Hirschsprung's disease and multiple anterior pituitary hormone deficiencies is described. The importance of endocrine assessment of such patients who show disturbance of growth or puberty is emphasized.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
9/13. Hirschsprung's disease associated with isolated familial medullary carcinoma of the thyroid.We present two siblings with neonatal Hirschsprung's disease in whom isolated familial medullary carcinoma of the thyroid was diagnosed at the age of 16 and 19 years. Rectal biopsy in each patient revealed total absence of ganglion cells in the myenteric plexus and hypertrophied nerve fibers characteristic of Hirschsprung's disease. Both underwent total thyroidectomy and histological examination revealed bilateral and multifocal medullary carcinoma of the thyroid. These two patients belong to a large family in whom another 12 affected members with medullary carcinoma of the thyroid were found. Our description is the first report of an association between Hirschsprung's disease and isolated familial medullary carcinoma of the thyroid. We suggest that familial occurrence of Hirschsprung's disease could be an early presentation of familial medullary carcinoma of the thyroid either as the isolated form or as part of multiple endocrine neoplasia type IIa or IIb.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
10/13. Hirschsprung's disease associated with a deletion of chromosome 10 (q11.2q21.2): a further link with the neurocristopathies?We report a patient with total colonic aganglionosis in association with a deletion of part of the long arm of chromosome 10: (del(10)(q11.2q21.2)). This deletion includes the ret proto-oncogene, which has recently been implicated in multiple endocrine neoplasia type 2a (men 2A). The possible links between Hirschsprung's disease and the neurocristopathies and the aetiological role of abnormalities of neural crest development in these conditions are discussed.- - - - - - - - - - ranking = 0.2keywords = endocrine (Clic here for more details about this article) |
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