Hereditary haemorrhagic telangiectasia: a clinical and scientific review

Govani, Fatima S; Shovlin, CL

doi:10.1038/ejhg.2009.35

Cited by 447 publications

(491 citation statements)

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“…HHT, 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.…”

Section: Overview Of Hhtmentioning

confidence: 99%

“…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 ). The mutated gene has some Blood Reviews _ HHT 2010_ Shovlin 4 influence on the resultant HHT phenotype, [22][23][24][25][26][27] although more profound variation in disease expression is seen between members of the same family.…”

Section: Overview Of Hhtmentioning

confidence: 99%

“…These considerations are recognised to centre on the degree of danger posed by particular silent lesions, the safety/tolerability of the screening method; the safety and efficacy of any treatments, and the overall potential advantage offered to the recipient in terms of better management. 3 Important general screening concepts have been articulated in recent publications 82,83 . These include the four possible outcomes if an abnormality is found by screening, and treated, and the tendency of potential recipients to consider only some of the potential outcomes (Table 3) 83 .…”

Section: 31) General Principlesmentioning

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: Overview Of Hhtmentioning

confidence: 99%

Section: Overview Of Hhtmentioning

confidence: 99%

Section: 31) General Principlesmentioning

confidence: 99%

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Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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“…HHT is an autosomal dominant disorder producing vascular malformations in multiple organs [21]. Small mucocutaneous telangiectasias typically occur in the oral cavity, nose, conjunctivae, and on the fingertips; AVMs occur in the lung (50% of HHT patients), liver (30%), brain (10%), and spine (1%) [22]. HHT patients represent a very small subset of patients with AVMs (approximately 2% of all AVM patients) [23,24].…”

Section: Geneticsmentioning

confidence: 99%

Central Nervous System Vascular Malformations

Davidson¹,

Stoodley²

2012

Congenital Anomalies - Case Studies and Mechanisms

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“…[1][2][3] Bleeding caused by HHT can occur anywhere in or on the body but is more frequent in specific regions of the body and rarely occurs on the skin. The most common symptom of HHT is epistaxis, which occurs in 95% of affected individuals.…”

Section: Introductionmentioning

confidence: 99%