Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation

Schwenter, Frank; Faughnan, Marie E.; Gradinger, Abigail B.; Berk, Terri; Gryfe, Robert; Pollett, Aaron; Cohen, Zane; Gallinger, Steven; Durno, Carol

doi:10.1007/s00535-012-0545-8

Cited by 47 publications

(31 citation statements)

References 40 publications

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“…JPS has been associated with germline mutations in three genes [SMAD4, BMPR1A (bone morphogenic protein receptor 1A), and ENG], all of which are part of the transforming growth factor-b signaling pathway [11]. The role of the PTEN gene mutation currently remains controversial, but this mutation can occur in conjunction with mutations of BMPR1A in patients with the rarest form juvenile polyposis of infancy, which is also associated with the highest morbidity and mortality.…”

Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 98%

“…In addition to surveillance for JPS, patients with this syndrome should undergo screening/precautions for the vascular malformations associated with hereditary hemorrhagic telangiectasia that include mucocutaneous telangiectasia, epistaxis, and ateriovenous malformations of the lungs, liver, and brain [11].…”

Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 99%

“…JPS-hereditary hemorrhagic telangiectasia overlap syndrome has recently been reported and can occur especially in patients with the SMAD4 mutation [9,11]. In addition to surveillance for JPS, patients with this syndrome should undergo screening/precautions for the vascular malformations associated with hereditary hemorrhagic telangiectasia that include mucocutaneous telangiectasia, epistaxis, and ateriovenous malformations of the lungs, liver, and brain [11].…”

Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 99%

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Colonic polyps and polyposis syndromes in pediatric patients

Kay¹,

Eng²,

Wyllie³

2015

Current Opinion in Pediatrics

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Pediatricians, pediatric gastroenterologists, and adult gastroenterologists caring for children should understand how to differentiate benign polyps in the pediatric age group from those associated with a higher risk of complications including recurrence risk and risk of development of intestinal or extraintestinal malignancy. Recent advances in genetic testing, as well as development of consensus guidelines, are key in the identification, screening, and follow-up of children and adolescents with polyposis syndromes.

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Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 98%

Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 99%

Section: Specific Polyposis Syndromes In Pediatric Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Colonic polyps and polyposis syndromes in pediatric patients

Kay¹,

Eng²,

Wyllie³

2015

Current Opinion in Pediatrics

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“…Other studies have reported the same observation (25,26). Aretz et al found that both BMPR1A and SMAD4 mutation carriers have various types of polyps.…”

Section: Discussionmentioning

confidence: 70%

JP–HHT phenotype in Danish patients with SMAD4 mutations

et al. 2015

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Patients with germline mutations in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT): the JP-HHT syndrome. The complete phenotypic picture of this syndrome is only just emerging. We describe the clinical characteristics of 14 patients with SMAD4-mutations. The study was a retrospective, register-based study. SMAD4 mutations carriers were identified through the Danish HHT-registry, the genetic laboratories - and the genetic departments in Denmark. The medical files from relevant departments were reviewed and symptoms of HHT, JPS, aortopathy and family history were noted. We detected 14 patients with SMAD4 mutations. All patients had polyps removed and 11 of 14 fulfilled the diagnostic criteria for JPS. Eight patients were screened for HHT-symptoms and seven of these fulfilled the Curaçao criteria. One patient had aortic root dilation. Our findings support that SMAD4 mutations carriers have symptoms of both HHT and JPS and that the frequency of PAVM and gastric involvement with polyps is higher than in patients with HHT or JPS not caused by a SMAD4 mutation. Out of eight patients screened for aortopathy, one had aortic root dilatation, highlighting the need for additional screening for aortopathy.

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“…The remaining 60 % of patients suspect for JPS have no known mutation. Patients with a SMAD4 mutation show a higher prevalence of gastric polyposis compared to patients with a BMPR1A mutation [4][5][6], and most SMAD4 patients also have hereditary haemorrhagic telangiectasia [7,8]. Establishing a diagnosis in patients with juvenile polyposis predominant in or limited to the stomach can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies.…”

Section: Introductionmentioning

confidence: 96%

Massive gastric polyposis associated with a germline SMAD4 gene mutation

et al. 2015

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Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98% of patients) and the stomach (14%). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endoscopic findings revealed giant rugal folds suggestive of Ménétrier disease. However, as other possible gastropathies could not be differentiated on the basis of histology, a definitive diagnosis of JPS required additional mutation analysis. In patients with polyposis predominant in or limited to the stomach, establishing a diagnosis based solely on the pathological features of polyps can be challenging due to difficulties in differentiating JPS from other hypertrophic gastropathies. Mutation analysis should be considered early in the diagnostic process in cases of suspected juvenile polyposis, thus facilitating rapid diagnosis and adequate follow-up.

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Juvenile polyposis, hereditary hemorrhagic telangiectasia, and early onset colorectal cancer in patients with SMAD4 mutation

Cited by 47 publications

References 40 publications

Colonic polyps and polyposis syndromes in pediatric patients

Colonic polyps and polyposis syndromes in pediatric patients

JP–HHT phenotype in Danish patients with SMAD4 mutations

Massive gastric polyposis associated with a germline SMAD4 gene mutation

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