Hereditary haemorrhagic telangiectasia: a clinical analysis.

Porteous, Mary; Burn, John; Proctor, S J

doi:10.1136/jmg.29.8.527

Cited by 202 publications

(139 citation statements)

References 7 publications

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“…In clinical practice, where an individual from an HHT family has only one further criterion but that criterion is a visceral AVM, the diagnosis of HHT is essentially confirmed, though not for research purposes. Conversely, the estimated probability of HHT-affected status for an apparently unaffected child of an HHT-affected parent ranges from 0.5 at birth, to 0.22 at 16 Blood Reviews _ HHT 2010_ Shovlin 20 years and 0.05 at 40 years 103,195,196 , 'Possible HHT' is preferred for the medical records of such individuals when young. 3 32…”

Section: ) Clinical Diagnosismentioning

confidence: 99%

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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attractive experimental therapies promoted in high profile publications when guidelines and reviews are quickly superseded.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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Section: ) Clinical Diagnosismentioning

confidence: 99%

“…Blood Reviews _ HHT 2010_ Shovlin 20 years and 0.05 at 40 years 103,195,196 , 'Possible HHT' is preferred for the medical records of such individuals when young. 3 32 Haematologists will note that Von Willebrand's Disease (VWD) can cause diagnostic confusion.…”

Section: ) Clinical Diagnosismentioning

confidence: 99%

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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“…The inheritance of at least one single mutant copy can predispose the individual to the development of the vascular abnormalities observed in HHT, which are modulated by several genetic, physiologic, and mechanical events (Porteous et al 1992). Little is known about the genetic basis of the observed clinical heterogeneity of HHT.…”

Section: Discussionmentioning

confidence: 99%

Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients

et al. 2007

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Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber disease is a systemic fibrovascular dysplasia with an autosomal dominant inheritance pattern. Mutations in two genes, endoglin and ALK-1, are known to cause HHT, both of which mediate signaling by transforming growth factor b ligands in vascular endothelial cells. Ten patients were analyzed. Diagnosis of HHT was carried out by means of family history, recurrent bleeding, and the presence of multiple telangiectases lesions. Conformation-sensitive gel electrophoresis analyses with consistent abnormal migration patterns were cloned and sequenced using the MegaBace 1000 DNA automated analyzer. Three novel mutations were identified in the coding sequence of the ALK-1 gene in five patients and their families, which demonstrated clinical manifestations of HHT type 2. These mutations included a G insertion and a T deletion of single base pairs in exons 3 and 7, as well as missense mutations in exons 7 and 8 of the ALK-1 gene. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity. We suggest the high rate of mutation detection and the small size of the ALK-1 gene make genomic sequencing a viable diagnostic test for HHT2.Keywords Activin receptor-like kinase 1 (ALK1) Á Endoglin (ENG) Á Hereditary hemorrhagic telangiectasia (HHT)

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“…Автор подчеркнул бледность кожных покровов и множественные ан гиомы у больных с НГТ и дифференцировал эту бо лезнь с гемофилией. Также исследователь предпо ложил, что болезнь может иметь наследственный характер: у отца упомянутого пациента были реци дивирующие желудочнокишечные кровотечения (ЖКК) и сосудистые «звездочки» на носу, языке, верхней губе, а мать и брат больного страдали реци дивирующими носовыми кровотечениями [1]. В 1900 г. W. Osler представил медицинской обще ственности троих пациентов с множественными со судистыми поражениями и рецидивирующими но совыми кровотечениями.…”

Section: историяunclassified

Hereditary hemorrhagic teleangiectasia: the topical problems of diagnostics and surgical treatment

Baydarova¹,

Тупикин²,

Andreytseva³

2016

Dok. gastroenterol.

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Hereditary haemorrhagic telangiectasia: a clinical analysis.

Cited by 202 publications

References 7 publications

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients

Hereditary hemorrhagic teleangiectasia: the topical problems of diagnostics and surgical treatment

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