Among patients with small aneurysms (< or = 7 mm), hypertension, relatively young age, and posterior circulation were significant risk factors for rupture. Given the minimal long-term morbidity and mortality of treatment of unruptured aneurysms in large, tertiary medical centers, management of unruptured aneurysms 7 mm or smaller should be governed by factors other than size, specifically age, history of hypertension, and location.

The identification of pathways that underlie common disease has been greatly impacted by the study of rare families that segregate single genes with large effect. Intracranial aneurysm is a common neurological problem; the rupture of these aneurysms constitutes a frequently catastrophic neurologic event. The pathogenesis of these aneurysms is largely unknown, although genetic and environmental factors are believed to play a role. Previous genomewide studies in affected relative pairs have suggested linkage to several loci, but underlying genes have not been identified. We have identified a large kindred that segregates nonsyndromic intracranial aneurysm as a dominant trait with high penetrance. Genomewide analysis of linkage was performed using a two-stage approach: an analysis of ~10,000 single-nucleotide polymorphisms in the 6 living affected subjects, followed by the genotyping of simple tandem repeats across resulting candidate intervals in all 23 kindred members. Analysis revealed significant linkage to a single locus, with a LOD score of 4.2 at 1p34.3-p36.13 under a dominant model with high penetrance. These findings identify a Mendelian form of intracranial aneurysm and map the location of the underlying disease locus.

Among patients with small aneurysms (< or = 7 mm), hypertension, relatively young age, and posterior circulation were significant risk factors for rupture. Given the minimal long-term morbidity and mortality of treatment of unruptured aneurysms in large, tertiary medical centers, management of unruptured aneurysms 7 mm or smaller should be governed by factors other than size, specifically age, history of hypertension, and location.

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