Genetics of intracranial aneurysms

THE ETIOLOGY AND pathogenesis of intracranial aneurysms are clearly multifactorial, with genetic factors playing an increasingly recognized role. Intracranial aneurysms have been associated with numerous heritable connective tissue disorders, which account for at least 5% of cases. Of these disorders, the most important are Ehlers-Danlos syndrome Type IV, Marfan's syndrome, neurofibromatosis Type 1, and autosomal dominant polycystic kidney disease; the association with intracranial aneurysms, however, has been firmly established only for polycystic kidney disease. Familial intracranial aneurysms are not rare but account for 7 to 20% of patients with aneurysmal subarachnoid hemorrhage and are generally not associated with any of the known heritable connective tissue disorders. First-degree relatives of patients with aneurysmal subarachnoid hemorrhage are at an approximately fourfold increased risk of suffering ruptured intracranial aneurysms, compared to the general population. Various possible modes of inheritance have been identified in families with intracranial aneurysms, suggesting genetic heterogeneity. Although the benefits have never been quantified, screening For asymptomatic intracranial aneurysms should be considered in families with two or more affected members. The yield of such a screening program may approximate 10%. Although it is unlikely that there is a single gene with major effect, much effort is currently being directed at locating intracranial aneurysm genes.