Affected twins in the familial intracranial aneurysm study

Jason Mackey, Robert D. Brown, Laura Sauerbeck, Richard Hornung, Charles J. Moomaw, Daniel L. Koller, Tatiana Foroud, Ranjan Deka, Daniel Woo, Dawn Kleindorfer, Matthew L. Flaherty, Irene Meissner, Craig Anderson, Guy Rouleau, E. Sander Connolly, John Huston, Joseph P. Broderick

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Abstract

Background and Purpose: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. Methods: The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. Results: A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. Conclusions: We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs.

Original languageEnglish (US)
Pages (from-to)82-86
Number of pages5
JournalCerebrovascular Diseases
Volume39
Issue number2
DOIs
StatePublished - Mar 6 2015

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Keywords

  • Concordance
  • Familial
  • Genetics
  • Intracranial aneurysm
  • Twins

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Mackey, J., Brown, R. D., Sauerbeck, L., Hornung, R., Moomaw, C. J., Koller, D. L., Foroud, T., Deka, R., Woo, D., Kleindorfer, D., Flaherty, M. L., Meissner, I., Anderson, C., Rouleau, G., Connolly, E. S., Huston, J., & Broderick, J. P. (2015). Affected twins in the familial intracranial aneurysm study. Cerebrovascular Diseases, 39(2), 82-86. https://doi.org/10.1159/000369961