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Age at intracranial aneurysm rupture among generations

Familial Intracranial Aneurysm Study

From the Departments of Neurology, Environmental Health, and Center for Environmental Genetics (D.W., R.H., L.S., J.B.), University of Cincinnati, OH; Department of Medical and Molecular Genetics (T.F.), Indiana University School of Medicine, Indianapolis; and Departments of Neurology and Neuroradiology (R.B., I.M., J.H.), Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr. Daniel Woo, Department of Neurology, University of Cincinnati College of Medicine, 231 Albert Sabin Way ML 0525, Cincinnati, OH 45267-0525 Daniel.Woo{at}uc.edu

Background: Previous studies have reported intracranial aneurysm (IA) occurring at young ages in subsequent generations. These studies did not correct for duration of follow-up. Second-generation members who would have their ruptured IA late in life may not be detected due to shorter follow-up time than the first generation. We examined families in which ruptured IA occurred in two consecutive generations for the hypothesis that the second generation (F1) was more likely to have a rupture at a younger age than the older generation (F0).

Methods: The Familial Intracranial Aneurysm (FIA) Study is a multicenter, international study recruiting families of ruptured and unruptured IA. All available family members are interviewed. Cox proportional hazards regression models and Kaplan-Meier curves were used to examine differences by generation.

Results: Although we found that the F1 generation was more likely to have an aneurysm rupture at a younger age than the F0 generation, we found that this was largely because of a lack of follow-up time in the F1 generation. The F1 generation had 50% the rupture rate of the prior generation. When analyzed by Kaplan-Meier curves, we found a tendency to have a slightly later rupture rate in the F1 generation once time to follow-up was included in the analysis model.

Conclusions: Families of ruptured intracranial aneurysm (IA) do not appear to demonstrate "anticipation." Our finding suggests that genetic epidemiology of ruptured IA should examine all types of variations such as single base-pair changes, deletions, insertions, and other variations that do not demonstrate anticipation.

FIA = familial intracranial aneurysm; IA = intracranial aneurysm; SAH = subarachnoid hemorrhage.

*See the appendix for a list of the Familial Intracranial Aneurysm (FIA) Study operational centers, recruitment centers, and investigators.

Funded by grants from the National Institute of Neurological Disorders and Stroke (R-O1 NS39512).

Disclosure: The authors report no disclosures.

Received April 3, 2008. Accepted in final form November 12, 2008.