Genotype–phenotype relationship for localization and age distribution of telangiectases in hereditary hemorrhagic telangiectasia

Letteboer, Tom G.W.; Mager, Hans‐Jurgen; Snijder, Repke J.; Lindhout, Dick; Amstel, Hans‐Kristian Ploos van; Zanen, Pieter; Westermann, Kees J.J.

doi:10.1002/ajmg.a.32243

Cited by 66 publications

(74 citation statements)

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“…HHT telangiectasia develop and get worse with age 103,104 (Fig 2a): Individual cutaneous lesions may regress, but overall, as recognised by the families, they generally become more prevalent in each individual with time. Currently, cerebral AVM development is thought to be complete during childhood, 68 and for most individuals, pulmonary AVMs by the end of puberty 105 .…”

Section: 1c) Age-related Changes In Hhtmentioning

confidence: 99%

Section: 2b) Genotype Phenotype Correlationsmentioning

confidence: 99%

“…A single series suggests HHT2 patients may have more pancreatic AVMs 9 , and develop dermal telangiectasia earlier than in HHT1. 104 There are no clear data to suggest that specific mutations within a particular HHT gene confer different HHT-related phenotypes.More recently described non-Curaçao features of HHT demonstrate stronger genotypephenotype correlations. Juvenile polyposis (JP) occurs in patients with SMAD4 mutations, when it appears to be indistinguishable from JP caused by BMPRIA mutations.…”

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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: 1c) Age-related Changes In Hhtmentioning

confidence: 99%

Section: 2b) Genotype Phenotype Correlationsmentioning

confidence: 99%

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Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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“…Примерно 53% больных НГТ имеют этот тип мутации [8,9]. Результаты исследований генотипа и фенотипа по казали, что у пациентов с НГТ1 чаще наблюдают ся легочные АВМ, чем при других подтипах НГТ [9,10].…”

Section: этиология и классификацияunclassified

“…Эту мутацию обнаруживают у 47% пациентов с НГТ. При НГТ2 симптомы по являются позже, чем при НГТ1, и чаще наблюда ются поражения печени [8,9]. В ходе дальнейших исследований выявили мута ции на хромосомах 5q31.332 (HГT3) и 7p14 (HГT 4), которые также являются причиной классической НГТ [13,14].…”

Section: этиология и классификацияunclassified

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

Baydarova¹,

Тупикин²,

Andreytseva³

2016

Dok. gastroenterol.

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Whole-Body Distribution and Clinical Association of Telangiectases in Systemic Sclerosis

et al. 2018

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IMPORTANCE In systemic sclerosis (SSc), to date, no study has precisely described the total number and fine distribution of telangiectases (TAs), their clinical association with the disease, and the biological mechanisms causing their development. OBJECTIVES To describe the whole-body distribution of TAs and assess the association between the whole-body TA number and the characteristics of patients with SSc. DESIGN, SETTING, AND PARTICIPANTS A single-center, cross-sectional study was conducted between July 11, 2016, and March 15, 2017, at the National Referral Centre for Rare Systemic and Autoimmune Diseases in France. A population-based sample of 106 adults who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc were included; 8 patients who had previously received laser treatment for TAs were excluded. MAIN OUTCOMES AND MEASURES The number of TAs on the whole body (total and those >5 mm) and TA distribution in different areas were recorded. The association with clinical and biological data was studied using univariate and multivariate linear regression. RESULTS A total of 106 patients (83 [78.3%] women) were enrolled, including 12 with precapillary pulmonary hypertension (PH). Mean (SD) age was 60.6 (13.5) years. Telangiectasia distribution was 37.2% on the face, 33.2% on the upper limbs, including 26.4% on the hands, 28.1% on the trunk, including 17.1% for the upper part of the trunk, and 1.5% on the lower limbs. In analysis using the multivariate linear regression model, the whole-body TA number was independently associated with male sex (percentage change, 144.4%; 95% CI, 7.5% to 455.9%; P = .03), PH (162.8%; 95% CI, 5.6% to 553.8%; P = .04), history of pulmonary embolism (336.4%; 95% CI, 39.0% to 1270.1%; P = .01), glomerular filtration rate (−1.6%; 95% CI, −3.2% to −0.1% per 1-mL/min/1.73 m 2 increase; P = .04), and soluble endoglin level (28.2%; 95% CI, 1.2% to 62.5% per 1-ng/mL increase; P = .04). Receiver operating characteristic analyses assessing the ability of TAs to identify the presence of PH revealed that the area under the curve was significant for the TA number on the whole body (0.77; 95% CI, 0.57 to 0.88), on the hands and face (0.81; 95% CI, 0.57 to 0.91), and on the hands (95% CI, 0.77; 95% CI, 0.57 to 0.89). CONCLUSIONS AND RELEVANCE In the patients in this study with SSc, TAs were predominantly located on the face, hands, and the upper part of the trunk. Telangiectases appeared to be associated with vasculopathy features of SSc, particularly with PH and soluble endoglin levels.

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Genotype–phenotype relationship for localization and age distribution of telangiectases in hereditary hemorrhagic telangiectasia

Cited by 66 publications

References 17 publications

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

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

Whole-Body Distribution and Clinical Association of Telangiectases in Systemic Sclerosis

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