Intracranial Hemorrhage in Infants and Children With Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)

Morgan, Terry K.; McDonald, Jamie; Anderson, Christina; Ismail, Mohammed; Miller, Franklin J.; Mao, Rong; Madan, Ashima; Barnes, Patrick D.; Hudgins, Louanne; Manning, Melanie A.

doi:10.1542/peds.109.1.e12

Cited by 122 publications

(95 citation statements)

References 49 publications

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“…115 In these series, there was no evidence for an increase in mortality in patients presenting later in life, 4 but an excess mortality in patients who had presented with HHT at a younger age, (<60 years) 4 or in young adults (in a series precluding childhood deaths). 115 These findings are in keeping with multiple other series that indicate early mortality due to AVMs, particularly cerebral AVM bleeds in childhood and young adults 68,88,116 , and pregnancy related maternal deaths 55,109 , although the article by Kjeldsen AD et al 4 , the strongest predictor of early mortality appeared to be the severity of nasal or gastrointestinal haemorrhage. More recent life expectancy data of 300 parents of HHT patients 117 , and 562 HHT-patients 118 suggest potentially better survival rates, although formal peer reviewed publication is awaited.…”

supporting

confidence: 79%

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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confidence: 79%

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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“…Whether this is due to a lower rate of pulmonary and cerebral manifestations in children is unclear. To date, frequency estimates of pulmonary and cerebral AVMs are based on case reports and small series [8,24,26,27,[40][41][42][43][44][45][46][47][48][49][50][51], and the diagnostic yield of initial diagnostic screening procedures in asymptomatic children has not been systematically evaluated.…”

mentioning

confidence: 99%

Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia

Al-Saleh¹,

Mei-Zahav²,

Me³

et al. 2009

European Respiratory Journal

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Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterised by vascular dysplasia complicated by visceral arteriovenous malformations (AVMs). To date, the diagnostic yield of screening procedures for pulmonary and cerebral AVMs in children with definite or potential HHT is not well defined. The aim of the present study was to prospectively evaluate the diagnostic yield of a screening protocol for pulmonary and cerebral AVMs in children with either a definite or potential HHT diagnosis.All children referred for evaluation for HHT between 1996 and 2008 were included in the present analysis. Screening tests for AVMs included chest computed tomography and brain magnetic resonance imaging.61 children with a definite clinical and/or genetic diagnosis of HHT were asymptomatic for visceral AVMs at their first baseline assessment (mean¡SD age 8.7¡4.7 yrs; range 0-17.0 yrs). Of these, 15 (25%) had pulmonary and/or cerebral AVMs diagnosed on initial screening tests. Pulmonary AVMs predominated in paediatric HHT patients (14 out of 15 patients) and were found in eight children aged ,10 yrs. 55 children had a potential HHT diagnosis as they fulfilled only one or two HHT clinical diagnostic criteria and did not have a confirmatory genetic diagnosis (age 10.9¡4.8 yrs; range 0-17.9 yrs). None of these children had pulmonary or cerebral AVMs on initial screening tests.The present data suggest that children with a definite HHT diagnosis have a high frequency of pulmonary AVMs even when clinically asymptomatic. In contrast, no AVMs were observed in children not fulfilling HHT diagnostic criteria. Genetic testing appears to be useful in defining an at-risk group for pulmonary AVMs in childhood.

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“…In these cases, the ICH is catastrophic and uniformly fatal, with most cases of AVM diagnosed on autopsy. 2,3 Here we report a newborn found to have HHT presenting with seizures and diagnosed with ICH from a suspected AVM who survived with aggressive medical management and surgical intervention.…”

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confidence: 96%

“…In the adult population with HHT, 20% have cerebrovascular malformations with the annual risk of intracranial hemorrhage (ICH) from unruptured AVMs of 2-4%. 2 The prevalence of cerebral AVMs among children with HHT is unknown and ICH secondary to HHT has been rarely reported in neonates. In these cases, the ICH is catastrophic and uniformly fatal, with most cases of AVM diagnosed on autopsy.…”

Section: Introductionmentioning

confidence: 99%

Term neonate with intracranial hemorrhage and hereditary hemorrhagic telangiectasia: a case report and review of the literature

et al. 2012

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Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs). The disease rarely presents in the neonatal period, primarily manifesting with epistaxis and gastrointestinal bleeding in adulthood. Occasionally, HHT can also present with symptoms related to AVMs in the cerebral, pulmonary or gastrointestinal vasculature. In prior reports, intracranial hemorrhage (ICH) secondary to cerebral AVM in neonates with HHT has been catastrophic and uniformly fatal. Here we report a case of a newborn with HHT and ICH from a suspected AVM who survived with aggressive medical management and surgical intervention, and provide a comprehensive review of the literature on ICH in neonates with HHT.

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Intracranial Hemorrhage in Infants and Children With Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)

Abstract: Our report shows that infants and children with a family history of HHT are at risk for sudden and catastrophic ICH. A preemptive diagnosis may potentially identify and prevent more serious sequelae.

Cited by 122 publications

References 49 publications

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Screening for pulmonary and cerebral arteriovenous malformations in children with hereditary haemorrhagic telangiectasia

Term neonate with intracranial hemorrhage and hereditary hemorrhagic telangiectasia: a case report and review of the literature

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