A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 ( SMAD4)

Gallione, Carol J.; Repetto, Gabriela M.; Legius, Eric; Rustgi, Anil K.; Schelley, Susan; Tejpar, Sabine; Mitchell, Grant A.; Drouin, Éric; Westermann, C. J. J.; Marchuk, Douglas A.

doi:10.1016/s0140-6736(04)15732-2

Cited by 682 publications

(542 citation statements)

References 27 publications

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“…Finally, involvement of the still unidentified HHT3 locus (Cole et al, 2005) cannot be ruled out as none of the four mutation-negative families was large enough to allow linkage analysis. Based on the absence of polyps in the gastrointestinal tract of our patients, the MADH4 gene (Gallione et al, 2004) mutations can be excluded.…”

Section: Discussionmentioning

confidence: 99%

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

et al. 2006

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Section: Discussionmentioning

confidence: 99%

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

et al. 2006

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“…Die Polypen treten im gesamten Dickdarm auf, KRKs finden sich in über 50 % im rechtsseitigen Kolon und in über 20 % im Rektosigmoid [265]. Aus diesem Grunde muss eine komplette Koloskopie zur Früherkennung durchgeführt werden [256,257,259,260] [380,381]. Daneben ist möglicher-weise das Risiko für Pankreaskarzinome erhöht [382 -386].…”

Section: Level Of Evidence 1cunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

147

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“…2 More recently recognised features include pulmonary arterial hypertension 10 ; juvenile polyposis 11 ; pulmonary hypertension in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [12][13][14][15][16] ; a prothrombotic state associated with elevated plasma levels of factor VIII 17 , and potential immune dysfunction. 18 Three of the genes mutated in HHT have been identified: endoglin (resulting in HHT1, OMIM #187300) 19 ; ACRVL1/ALK1; (resulting in HHT2, OMIM#600376) 20 , and more rarely, SMAD4 (mutated in HHT in association with juvenile polyposis, JPHT OMIM #175050) 11 . Many hundreds of different mutations have been described in HHT families, with no common mutation identified ( 21 , summarised in 3 ).…”

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Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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Hereditary haemorrhagic telangiectasia, inherited as an autosomal dominant trait, affects approximately 1 in 5,000 people. The abnormal vascular structures in HHT result from mutations in genes (most commonly endoglin or ACVRL1) whose protein products influence TGF-ß superfamily signalling in vascular endothelial cells. The cellular mechanisms underlying the generation of HHT telangiectasia and arteriovenous malformations are being unravelled, with recent data focussing on a defective response to angiogenic stimuli in particular settings. For affected individuals, there is often substantial morbidity due to sustained and repeated haemorrhages from telangiectasia in the nose and gut. Particular haematological clinical challenges include the management of severe iron deficiency anaemia; handling the intricate balance of antiplatelet or anticoagulants for HHT patients in whom there are often compelling clinical reasons to use such agents; and evaluation of apparently attractive experimental therapies promoted in high profile publications when guidelines and reviews are quickly superseded. There is also a need for sound screening programmes for silent arteriovenous malformations. These occur commonly in the pulmonary, cerebral, and hepatic circulations, may haemorrhage, but predominantly result in more complex pathophysiology due to consequences of defective endothelium, or shunts that bypass specific capillary beds. This review will focus on the new evidence and concepts in this complex and fascinating condition, placing these in context for both clinicians and scientists, with a particular emphasis on haematological settings. Blood Reviews _ HHT 2010_ Shovlin 3 Overview of HHTHHT, also known as Osler Weber Rendu syndrome [1][2][3] , is one of the most common disorders to be inherited as an autosomal dominant trait. Careful epidemiological studies reveal that it affects approximately 1 in 5,000 individuals, 4,5 with regional differences, 6 and isolated communities displaying higher prevalences due to founder effects. 7 8 HHT was first described as a familial disease characterised by severe recurrent nasal and gastrointestinal bleeding with associated anaemia, and visible dilated blood vessels (telangiectasia) on the lips and finger tips. The majority of HHT patients are also affected by larger arteriovenous malformations (AVMs) in the pulmonary, hepatic, cerebral, pancreatic, spinal and other circulations. 1,2,9 These features, presented in more detail within Table 1, are used as criteria to diagnose HHT. 2 The spectrum of disease within the HHT umbrella has extended beyond the telangiectatic/AVM HHT pathology delineated by the Curaçao criteria. 2 More recently recognised features include pulmonary arterial hypertension 10 ; juvenile polyposis 11 ; pulmonary hypertension in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [12][13][14][15][16] ; a prothrombotic state associated with elevated plasma levels of factor VIII 17 , and poten...

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A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 ( SMAD4)

Cited by 682 publications

References 27 publications

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

DHPLC-based mutation analysis of ENG and ALK-1 genes in HHT Italian population

S3-Leitlinie – Kolorektales Karzinom

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

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