Genetics of intracranial aneurysms.

BACKGROUND AND PURPOSE Genetic determinants probably play a role in the development of intracranial aneurysms. We review the present knowledge on this issue. METHODS This work entailed a comprehensive search of the literature, a critical appraisal of the identified papers, and a personal view of limitations and future directions. RESULTS We identified 10 genome-wide linkage studies in families and sib pairs with intracranial aneurysms. These studies have identified several loci, but only 4 (1p34.3-p36.13, 7q11, 19q13.3, and Xp22) have been replicated in different populations. For the loci on 1p34.3-p36.13 and 7q11 association with positional candidate genes has also been demonstrated: for locus on 1p34.3-p36.13 association with the perlecan gene and for 7q11 association with the elastin and collagen type 1 A2 genes. CONCLUSIONS The progress in identifying genetic determinants for intracranial aneurysms is modest. Reasons for this modest progress include limitations of the present studies, limitations because of the nature of the disease, and limitations in our concept of aneurysms and aneurysm development. Future studies may benefit from strict definitions of familial aneurysms, reduced phenotypic heterogeneity (separating ruptured from unruptured aneurysms, and within these subsets probably also reduce morphological heterogeneity, eg, by grouping similar sites of aneurysms), taking into account age and other risk factors of the patients with aneurysms, and sufficiently large numbers of patients. In future studies we should not only look for genetic determinants of aneurysms, but also for genetic determinants of rupture of aneurysms. This would help in selecting patients for preventive treatment of aneurysms.