Genetics of Intracranial Aneurysms

Intracranial aneurysms (IAs) are localized dilatations of intracranial arteries that are because of weaknesses of the endothelial layer. These dilations vary in size (small aneurysms, 25 mm) and are classified according to their shapes: either localized sac-like pouches or long dilatations that increase the vessels diameter; these shapes are referred to, respectively, as saccular or berry aneurysms and fusiform aneurysms. Most IAs are saccular and typically occur at the arterial branching sites of the circle of Willis. Common sites of saccular IAs include the anterior communicating artery, the posterior communicating artery, internal carotid artery, the middle cerebral artery, and the basilar artery bifurcation. Although the exact pathogenesis of IA remains to be established, several hypotheses have highlighted the contribution of maladaptive vascular remodeling triggered by hemodynamic stress and inflammatory response1—a chain of events that would ultimately damage blood vessel walls and lead to IA. The worldwide prevalence of IA is estimated to be ≈3.2%.2 Subarachnoid hemorrhage (SAH) accounts for ≈5% of all strokes, and 85% of SAHs are because of aneurysmal ruptures. SAH has an incidence rate of 9 per 10 000 persons per year and a fatality rate ≈50%.3 The incidence of SAH is markedly higher in the Finnish and Japanese populations, but surprisingly, this is not because of the prevalence of IA in these populations.2 The most common clinical symptoms of aneurysmal SAH are a sudden onset of severe headache with stiff neck, vomiting, and photophobia. Unruptured IAs are usually asymptomatic and are identified through the screening of high-risk individuals or as incidental findings of magnetic resonance imaging, particularly magnetic resonance angiogram, or computerized tomographic studies. The diagnosis of IA is made by magnetic resonance angiogram, computerized tomographic angiography, or classical angiography. The diagnosis of …