Identical twins with hereditary hemorrhagic telangiectasia concordant for cerebrovascular arteriovenous malformations

Lesser, Barry A.; Wendt, David; Miks, Veronica M.; Norum, Robert A.

doi:10.1016/0002-9343(86)90372-4

Cited by 14 publications

(5 citation statements)

References 12 publications

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“…14,20,22,[41][42][43][44] There are 5 prior reports of familial AVMs in HHT. 20,[45][46][47][48] Our series includes 3 patients harboring an AVM who were sibling members of a single family. It is possible that a family history of a first-degree relative with a cerebral AVM or intracranial hemorrhage may be a risk factor for AVM in the HHT population, but more data are needed to clarify this relationship.…”

Section: Resultsmentioning

confidence: 99%

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Maher¹,

Piepgras²,

Brown³

et al. 2001

Stroke

214

104

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Background and Purpose-Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for developing cerebral vascular malformations and pulmonary arteriovenous fistulae. We assessed the risk of neurological dysfunction from these malformations and fistulae. Methods-Three hundred twenty-one consecutive patients with HHT seen at a single institution over a 20-year period were studied. Any evidence of prior neurological symptoms or presence of an intracranial vascular malformation was recorded. All cases of possible cerebral arteriovenous malformation were confirmed by conventional arteriography. Results-Twelve patients (3.7%) had a history of cerebral vascular malformations. Ten patients had arteriovenous malformations, 1 had a dural arteriovenous fistula, and 1 had a cavernous malformation. Seven patients (2.1%) presented with intracranial hemorrhage, 2 presented with seizures alone, and 3 were discovered incidentally. The average age at the time of symptomatic intracranial hemorrhage was 25.4 years. All patients with a history of intracranial hemorrhage were classified as Rankin grade I or II at a mean follow-up interval of 6.0 years. A history of cerebral infarction or transient ischemic attack was found in 29.6% of patients with HHT and a pulmonary arteriovenous fistula. Conclusions-The risk of intracranial hemorrhage is low among people with HHT. Furthermore, a majority of these patients have a good functional outcome after hemorrhage. The data do not suggest a compelling indication for routine screening of patients with HHT for asymptomatic cerebral vascular malformations. 1 The estimated prevalence is 1 or 2 cases per 100 000. 1,2 Chromosomes 9q and 12q have been implicated in the inheritance of this disease. 3-7 A family history of HHT, although not required to make the diagnosis, is almost universally present. The vascular malformations of HHT may occur in multiple organs, including the lung, liver, kidney, and brain. 8,9 Epistaxis is the most common presentation, followed by gastrointestinal bleeding. 10,11 Pulmonary arteriovenous fistulae (AVFs) are often accompanied by dyspnea or hemoptysis and, less frequently, ischemic neurological symptoms. [12][13][14] Telangiectasias are frequently noted on the skin and mucous membranes, often not appearing until the second or third decade. 8,9 Brown et al 15,16 have reported that the detection rate of intracranial vascular malformations in a population-based study in the most recent time period was 2.75 per 100 000 person-years. The prevalence of intracranial hemorrhage from a vascular malformation was 7.50 per 100 000 people in the population at large. 15,16 Patients with HHT are thought to be at increased risk for harboring cerebral vascular malformations compared with the entire population. Arteriovenous malformations (AVMs), cavernous malformations, dural arteriovenous fistulae, and aneurysms have all been reported in these patients ( Figure 1). 14,17-24 Vascular malformations are found throughout the central nervous system, including the spinal cor...

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Section: Resultsmentioning

confidence: 99%

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Maher¹,

Piepgras²,

Brown³

et al. 2001

Stroke

214

104

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“…Familial clustering of BAVMs has been reported in patients with HHT 7 33. Nidus-type BAVMs are not the only BAVMs found in HHT, but intracranial arteriovenous fistulae, micro-AVMs and spinal vascular malformations, or a combination of these, in both children and adults (mean age 15 years, range 0–60) are also found 34.…”

Section: Discussionmentioning

confidence: 96%

Familial occurrence of brain arteriovenous malformations: a systematic review

Beijnum

Worp

Schippers

et al. 2007

Journal of Neurology, Neurosurgery & Psychiatry

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Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

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“…Occasional familial clustering of cerebral135 136 and pulmonary119 involvement had been described but it was not clear whether this represented chance occurrences in a disease in which only some members of an affected family developed any particular complication.…”

Section: Current Understandings Of Mechanismsmentioning

confidence: 99%

Rare diseases bullet 4: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms

Shovlin¹,

Letarte²

1999

Thorax

356

310

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Hereditary haemorrhagic telangiectasia (HHT, Rendu-Osler-Weber syndrome) exemplifies an important group of diseases which have catalysed advances in the understanding of fundamental pathophysiological mechanisms. In this paper areas of clinical management of HHT are discussed and the molecular pathogenesis is reviewed. The first section is aimed at all clinicians and concentrates on the recognition of a disorder in which silent cerebral and pulmonary involvement may be life threatening if left untreated. Recent data concerning the diagnostic and treatment modalities for pulmonary arteriovenous malformations (PAVMs) are also reviewed, and the growing concern that many patients with HHT may have small or residual PAVMs is highlighted. The paucity of good longitudinal data on these patients and others with diVerent forms of HHT highlights the need for further clinical studies. In the second section the results of molecular research which suggests a role for receptors and ligands of the transforming growth factor (TGF)-superfamily in the pathogenesis of this vascular disease are discussed. The means by which such information may relate to the clinical heterogeneity observed in HHT are specifically addressed, and more fundamental questions such as how reduced cell surface expression of endoglin predisposes a patient to develop PAVMs are also discussed. Hereditary haemorrhagic telangiectasiaThe classical patient with the vascular disorder hereditary haemorrhagic telangiectasia (HHT) has nose bleeds, dilated blood vessels over the lips and finger tips, and gastrointestinal bleeding in later life. However, this clinical scenario represents only one of the presentation patterns of HHT.1 2 It is now recognised that, in addition to microscopic mucocutaneous telangiectases derived from post capillary venules ( fig 1A), 3 HHT leads to the development of larger abnormal vascular structures at other sites. Arteriovenous malformations in the pulmonary, cerebral, and hepatic circulations account for some of the most devastating clinical complications of the disease.The autosomal dominant inheritance pattern of HHT has enabled identification of the underlying genetic defects, prompting increased scientific interest in the disorder. Mutations in at least two genes have been shown to be associated with HHT in diVerent families: endoglin on chromosome 9, 4 and ALK-1 (activin receptor-like kinase 1) on chromosome 12.5 Both genes encode endothelial cell transmembrane proteins that can be defined as components of the receptor complexes for growth factors of the TGF-super- Figure 1 Hereditary haemorrhagic telangiectasia (HHT). (A) Mucocutaneous

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Identical twins with hereditary hemorrhagic telangiectasia concordant for cerebrovascular arteriovenous malformations

Cited by 14 publications

References 12 publications

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Familial occurrence of brain arteriovenous malformations: a systematic review

Rare diseases bullet 4: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms

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