Aneurysm, Intracranial Berry, 9

Description

Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006).

For a discussion of genetic heterogeneity of intracranial berry aneurysms, see ANIB1 (105800).

Mapping

In a genomewide association study of 920 Finnish patients with intracranial aneurysm and 985 controls, Bilguvar et al. (2008) found a significant association with rs700651 on chromosome 2q. The association was replicated in a Dutch cohort of 781 cases and 6,424 controls and a Japanese cohort of 495 cases and 676 controls. The combined p value was 4.4 x 10(-8) with an odds ratio of 1.24.

Molecular Genetics

Berry aneurysm may have an increased frequency in persons with Ehlers-Danlos syndrome type IV (130050), which is caused by mutation in the type III collagen gene (COL3A1; 120180) on chromosome 2q. Ostergaard and Oxlund (1987) sampled the middle cerebral artery and brachial artery postmortem in 14 patients who died following rupture of intracranial saccular aneurysms and from a control group of 14 age- and sex-matched patients who died of causes unrelated to aneurysm rupture. In 6 of the 14 patients, deficiency of type III collagen was demonstrated in the specimens from the middle cerebral artery. De Paepe et al. (1988) proposed that a defect in type III collagen may be responsible for familial multiple intracranial aneurysms, perhaps with few signs suggesting Ehlers-Danlos syndrome type IV. The same suggestion had been made by Pope et al. (1981). The experience of Kuivaniemi et al. (1993), however, suggested that mutations in the COL3A1 gene are not a common cause of intracranial aneurysms or of cervical artery dissections. They studied type III collagen cDNA from 58 patients of 7 different nationalities with one or the other of these diagnoses. Among the patients studied were 3 pairs of relatives; among the others 29 had at least 1 blood relative with either an intracranial artery aneurysm or a cervical artery dissection. The age of the patients at the time of diagnosis ranged from 15 to 68 years. The study group consisted of 25 males and 33 females. Mutations in the coding sequence for the triple-helical domain were excluded in 40 individuals with intracranial aneurysms and 18 individuals with cervical artery dissections. Mutations that markedly decreased expression from 1 allele were also excluded in 42 of the 58 individuals.