Hereditary generalized juvenile polyposis: Association with arteriovenous malformations and risk of malignancy

Radin, D R

doi:10.1007/bf00203488

Cited by 15 publications

(5 citation statements)

References 8 publications

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“…In the aggregate, this SMAD4 mutation‐positive JP–HHT cohort displayed the full range of clinical features associated with HHT as defined by the Curaçao criteria [Shovlin et al, 2000]. Thirteen patients exhibited PAVMs, consistent with previous reports of JP patients with PAVMs [Cox et al, 1980; Conte et al, 1982; Baert et al, 1983; Prieto et al, 1990; Radin, 1994; Schumacher et al, 1994; Desai et al, 1998; Inoue et al, 1999; Burger et al, 2002]. One patient with a PAVM also had a liver AVM, and one patient with a PAVM also had a cerebral AVM.…”

Section: Resultssupporting

confidence: 82%

“…Although there had been reports in the medical literature of JP patients with associated HHT or HHT‐like symptoms, most notably pulmonary AVMs (PAVMs), these observations did not originally point to any specific genetic cause [Cox et al, 1980; Conte et al, 1982; Baert et al, 1983; Prieto et al, 1990; Radin, 1994; Schumacher et al, 1994; Desai et al, 1998; Ballauff and Koletzko, 1999; Inoue et al, 1999]. A combined syndrome, JP–HHT, is now recognized [Gallione et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

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Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome

Gallione

Aylsworth

Beis

et al. 2010

American J of Med Genetics Pt A

140

136

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Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP and JP-HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all of the SMAD4 mutations in the JP-HHT patients were clustered in the COOH-terminal MH2 domain of the protein. If valid, this correlation would provide a molecular explanation for the phenotypic differences, as well as a pre-symptomatic diagnostic test to distinguish patients at risk for the overlapping but different clinical features of the disorders. In this study, we collected 19 new JP-HHT patients from which we identified 15 additional SMAD4 mutations. We also reviewed the literature for other reports of JP patients with HHT symptoms with confirmed SMAD4 mutations. Our combined results show that although the SMAD4 mutations in JP-HHT patients do show a tendency to cluster in the MH2 domain, mutations in other parts of the gene also cause the combined syndrome. Thus, any mutation in SMAD4 can cause JP-HHT. Any JP patient with a SMAD4 mutation is, therefore, at risk for the visceral manifestations of HHT and any HHT patient with SMAD4 mutation is at risk for early onset gastrointestinal cancer. In conclusion, a patient who tests positive for any SMAD4 mutation must be considered at risk for the combined syndrome of JP-HHT and monitored accordingly.

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Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome

Gallione

Aylsworth

Beis

et al. 2010

American J of Med Genetics Pt A

140

136

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“…Previous studies reported that JP patients sometimes exhibit various extraintestinal manifestations. Among such manifestations, pulmonary arteriovenous malformations are the most frequently described [Cox et al, 1980; Baert et al, 1983; Prieto et al, 1990; Radin, 1994; Schumacher et al, 1994; Inoue et al, 1999; Gillespie and McIvor, 2001]. Recently, a combined syndrome of JP and HHT was suggested [Gallione et al, 2004].…”

Section: Discussionmentioning

confidence: 99%

Gastric juvenile polyposis associated with germline SMAD4 mutation

Shikata

Kukita

Matsumoto

et al. 2005

American J of Med Genetics Pt A

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We treated a 39-year-old woman with hypoproteinemia and anemia who had profuse gastric polyposis. Radiographic and endoscopic examination showed numerous polyps restricted to the stomach. The patient had pulmonary arteriovenous malformations in the left lung. Histological examination of the resected stomach revealed the gastric polyposis to be composed of cystic dilatation of the glands with small areas of adenocarcinoma. These findings were compatible with gastric juvenile polyposis (GJP) accompanied by gastric cancer. Analysis of genomic DNA revealed that the patient had truncating mutation of SMAD4, a responsible gene for juvenile polyposis (JP). Our case suggests that SMAD4 is possibly a responsible gene for GJP.

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“…Hereditary hemorrhagic teleangiectasia (Osler-Weber-Rendu syndrome) is an autosomal dominant Although considerable variation in reports exists, it seems evident that JP patients carry an increased risk of colorectal and possibly gastric cancer. Case reports of juvenile polyposis patients with symptoms of HHT, including arteriovenous malformations in the lung [80][81][82][83], liver [82,83], and skin [83] and gastrointestinal teleangiectasias [81,82], raised the suggestion of a common genetic cause for these two syndromes. (4).…”

Section: Extra-intestinal Manifestationsmentioning

confidence: 99%

“…In JP patients with germline SMAD4 or ENG mutations, screening should be considered for arteriovenous malformations using chest radiography, magnetic resonance imaging of the brain and liver sonography [82,84]. In addition, digital clubbing and pulmonary osteoarthropathy are frequently described in combination with arteriovenous malformations [78,80].…”

Section: Genetic Defectmentioning

confidence: 99%

Gastrointestinal Polyposis Syndromes

Brosens¹,

Hattem²,

Jansen³

et al. 2007

CMM

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Colorectal cancer is one of the leading causes of cancer-related death in the Western society, and the incidence is rising. Rare hereditary gastrointestinal polyposis syndromes that predispose to colorectal cancer have provided a model for the investigation of cancer initiation and progression in the general population. Many insights in the molecular genetic basis of cancer have emerged from the study of these syndromes. This review discusses the genetics and clinical manifestations of the three most common syndromes with gastrointestinal polyposis and an increased risk of colorectal cancer: familial adenomatous polyposis (FAP), juvenile polyposis (JP) and Peutz-Jeghers syndrome (PJS).

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Hereditary generalized juvenile polyposis: Association with arteriovenous malformations and risk of malignancy

Cited by 15 publications

References 8 publications

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP–HHT syndrome

Gastric juvenile polyposis associated with germline SMAD4 mutation

Gastrointestinal Polyposis Syndromes

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