NEW YORK (Reuters Health) – People with a family history of intracranial aneurysm are known to be at increased risk themselves, but now new research questions prior findings suggesting that aneurysm rupture does not, in fact, occur earlier in successive generations, a phenomenon referred to as “genetic anticipation.”

In previous studies, aneurysm rupture has been reported to occur as much as 20 years younger in a second generation of patients relative to the first. However, these studies did not control for the duration of follow-up. If, for example, a second generation patient had short follow-up, it is possible that a rupture late in life would be missed, skewing the results.

In the Familial Intracranial Aneurysm Study, Dr. Daniel Woo, from the University of Cincinnati College of Medicine, and colleagues analyzed data from 1641 subjects from 429 aneurysm families to assess whether aneurysm ruptures occurs earlier in successive generations. The study focused on the 54 families that had ruptures in both an older generation and a second generation of members.

According to the report in the February 24th issue of Stroke, aneurysm rupture occurred earlier in the second generation than in the older generation. After accounting for duration of follow-up, however, this difference largely disappeared and there was even evidence that ruptures occurred slightly later in the second generation.

“Genetic anticipation suggests an ‘accumulation’ of risk over generations, the classic example of which is instability of multinucleotide repeats,” the authors write.

“However, ruptured intracranial aneurysm is likely to be a complex trait with multiple genetic and environmental risk factors interacting with one another,” they note. “As such, it is unlikely to demonstrate genetic anticipation.”

Reference:
Neurology 2009;72:695-698.