Familial occurrence of brain arteriovenous malformations: a systematic review

Abstract

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.

Familial brain arteriovenous malformation maps to 5p13–q14, 15q11–q13 or 18p11: Linkage analysis with clipped fingernail DNA on high-density SNP array

“…The prevalence of AVM is estimated to be approximately 0.01% and the detection rate ranges between 1.12-1.34 per 100 000 person years [1,2]. Although most cases of AVM are sporadic, a total of 53 patients from 25 families have been reported [4]. Familial brain AVM is defined when it occurs in two or more relatives (up to third-degree relative) in a family without associated disorders such as hereditary hemorrhagic telangiectasia (HHT), is autosomal dominant multisystemic vascular dysplasia [4,5].…”

“…Although most cases of AVM are sporadic, a total of 53 patients from 25 families have been reported [4]. Familial brain AVM is defined when it occurs in two or more relatives (up to third-degree relative) in a family without associated disorders such as hereditary hemorrhagic telangiectasia (HHT), is autosomal dominant multisystemic vascular dysplasia [4,5]. It is plausible that familial cases are more frequent and could be overlooked because of asymptomatic conditions in other relatives.…”

Role of Embolization for Cerebral Arteriovenous Malformations

“…Various studies have reported an association with conditions such as hereditary hemorrhagic telangiectasia, Sturge-Weber disease, and WyburnMason syndrome. [6][7][8][9] AVMs often present with intracranial hemorrhage, but seizure, headache, and focal neurological deficits may also be seen. An annual hemorrhage risk of 2% to 4% is typically quoted and is associated with a 5% to 25% risk of death and 10% to 50% risk of neurological disability.…”

Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations

“…Although rare, familial cases of AVM outside the context of HHT have been reported in the literature [30,63]. A recent review article examined all case reports and identified 53 patients without HHT in 25 families with AVMs, mostly of first-degree relationships (79%) [63].…”

“…A recent review article examined all case reports and identified 53 patients without HHT in 25 families with AVMs, mostly of first-degree relationships (79%) [63]. While no clear pattern of inheritance emerged from the pedigrees, the clinical characteristics of familial AVM patients did not differ significantly from sporadic AVM, except for a younger age at diagnosis.…”