Skip to main content

The Genetics of Cerebral Aneurysms and Other Vascular Malformations

  • Chapter
  • First Online:
Stroke Genetics

Abstract

Stroke can be caused by vascular malformations and cerebral aneurysms. This chapter discusses the importance of these conditions and the genetic screening that could be used. This chapter also describes the most recent genes that have been associated with these conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 159.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 209.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ingall T, Asplund K, Mahonen M, Bonita R. A multinational comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke. 2000;31(5):1054–61.

    PubMed  CAS  Google Scholar 

  2. Brown Jr RD, Wiebers DO, Torner JC, O’Fallon WM. Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population-based study of intracranial vascular malformations in Olmsted Country, Minnesota. J Neurosurg. 1996;85(1):29–32.

    PubMed  Google Scholar 

  3. Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med. 1992;326(11):733–6.

    PubMed  CAS  Google Scholar 

  4. Fogelholm R. Subarachnoid hemorrhage in Finland. Stroke. 1992;23(3):437.

    PubMed  CAS  Google Scholar 

  5. Thrift AG, Dewey HM, Macdonell RA, McNeil JJ, Donnan GA. Incidence of the major stroke subtypes: initial findings from the North East Melbourne stroke incidence study (NEMESIS). Stroke. 2001;32(8):1732–8.

    PubMed  CAS  Google Scholar 

  6. Longstreth Jr WT, Koepsell TD, Yerby MS, van Belle G. Risk factors for subarachnoid hemorrhage. Stroke. 1985;16(3):377–85.

    PubMed  Google Scholar 

  7. Juvela S. Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage. Arch Neurol. 1996;53(8):734–40.

    PubMed  CAS  Google Scholar 

  8. Kissela BM, Sauerbeck L, Woo D, Khoury J, Carrozzella J, Pancioli A, et al. Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke. 2002;33(5):1321–6.

    PubMed  Google Scholar 

  9. Sankai T, Iso H, Shimamoto T, Kitamura A, Naito Y, Sato S, et al. Prospective study on alcohol intake and risk of subarachnoid hemorrhage among Japanese men and women. Alcohol Clin Exp Res. 2000;24(3):386–9.

    PubMed  CAS  Google Scholar 

  10. Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic stroke. The Honolulu Heart Program. JAMA. 1986;255(17):2311–4.

    PubMed  CAS  Google Scholar 

  11. Chyatte D, Chen TL, Bronstein K, Brass LM. Seasonal fluctuation in the incidence of intracranial aneurysm rupture and its relationship to changing climatic conditions. J Neurosurg. 1994;81(4):525–30.

    PubMed  CAS  Google Scholar 

  12. Feigin VL, Anderson CS, Anderson NE, Broad JB, Pledger MJ, Bonita R. Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997. Stroke. 2001;32(3):613–9.

    PubMed  CAS  Google Scholar 

  13. Gallerani M, Portaluppi F, Maida G, Chieregato A, Calzolari F, Trapella G, et al. Circadian and circannual rhythmicity in the occurrence of subarachnoid hemorrhage. Stroke. 1996;27(10):1793–7.

    PubMed  CAS  Google Scholar 

  14. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29(1):251–6.

    PubMed  CAS  Google Scholar 

  15. Atkinson JL, Sundt Jr TM, Houser OW, Whisnant JP. Angiographic frequency of anterior circulation intracranial aneurysms. J Neurosurg. 1989;70(4):551–5.

    PubMed  CAS  Google Scholar 

  16. Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, et al. Incidental findings on brain MRI in the general population. N Engl J Med. 2007;357(18):1821–8.

    PubMed  CAS  Google Scholar 

  17. Ronkainen A, Hernesniemi J, Puranen M, Niemitukia L, Vanninen R, Ryynanen M, et al. Familial intracranial aneurysms. Lancet. 1997;349(9049):380–4.

    PubMed  CAS  Google Scholar 

  18. Raaymakers TW. Aneurysms in relatives of patients with subarachnoid hemorrhage: frequency and risk factors. MARS Study Group. Magnetic resonance angiography in relatives of patients with subarachnoid hemorrhage. Neurology. 1999;53(5):982–8.

    PubMed  CAS  Google Scholar 

  19. Schievink WI, Schaid DJ, Michels VV, Piepgras DG. Familial aneurysmal subarachnoid hemorrhage: a community-based study. J Neurosurg. 1995;83(3):426–9.

    PubMed  CAS  Google Scholar 

  20. Schievink WI, Schaid DJ, Rogers HM, Piepgras DG, Michels VV. On the inheritance of intracranial aneurysms. Stroke. 1994;25(10):2028–37.

    PubMed  CAS  Google Scholar 

  21. De Braekeleer M, Perusse L, Cantin L, Bouchard JM, Mathieu J. A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada). Ann Hum Genet. 1996;60(Pt 2):99–104.

    PubMed  Google Scholar 

  22. Wang PS, Longstreth Jr WT, Koepsell TD. Subarachnoid hemorrhage and family history. A population-based case-control study. Arch Neurol. 1995;52(2):202–4.

    PubMed  CAS  Google Scholar 

  23. Broderick JP, Brown Jr RD, Sauerbeck L, Hornung R, Huston 3rd J, Woo D, et al. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke. 2009;40(6):1952–7.

    PubMed  Google Scholar 

  24. Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–10.

    PubMed  Google Scholar 

  25. Woo D, Khoury J, Haverbusch MM, Sekar P, Flaherty ML, Kleindorfer DO, et al. Smoking and family history and risk of aneurysmal subarachnoid hemorrhage. Neurology. 2009;72(1):69–72.

    PubMed  CAS  Google Scholar 

  26. Bromberg JE, Rinkel GJ, Algra A, van Duyn CM, Greebe P, Ramos LM, et al. Familial subarachnoid hemorrhage: distinctive features and patterns of inheritance. Ann Neurol. 1995;38(6):929–34.

    PubMed  CAS  Google Scholar 

  27. Wills S, Ronkainen A, van der Voet M, Kuivaniemi H, Helin K, Leinonen E, et al. Familial intracranial aneurysms: an analysis of 346 multiplex Finnish families. Stroke. 2003;34(6):1370–4.

    PubMed  Google Scholar 

  28. Onda H, Kasuya H, Yoneyama T, Takakura K, Hori T, Takeda J, et al. Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet. 2001;69(4):804–19.

    PubMed  CAS  Google Scholar 

  29. Hashikata H, Liu W, Inoue K, Mineharu Y, Yamada S, Nanayakkara S, et al. Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients. Stroke. 2010;41(6):1138–44.

    PubMed  CAS  Google Scholar 

  30. van der Voet M, Olson JM, Kuivaniemi H, Dudek DM, Skunca M, Ronkainen A, et al. Intracranial aneurysms in Finnish families: confirmation of linkage and refinement of the interval to chromosome 19q13.3. Am J Hum Genet. 2004;74(3):564–71.

    PubMed  Google Scholar 

  31. Farnham JM, Camp NJ, Neuhausen SL, Tsuruda J, Parker D, MacDonald J, et al. Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm. Hum Genet. 2004;114(3):250–5.

    PubMed  Google Scholar 

  32. Ruigrok YM, Seitz U, Wolterink S, Rinkel GJ, Wijmenga C, Urban Z. Association of polymorphisms and haplotypes in the elastin gene in Dutch patients with sporadic aneurysmal subarachnoid hemorrhage. Stroke. 2004;35(9):2064–8.

    PubMed  CAS  Google Scholar 

  33. Akagawa H, Tajima A, Sakamoto Y, Krischek B, Yoneyama T, Kasuya H, et al. A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Hum Mol Genet. 2006;15(10):1722–34.

    PubMed  CAS  Google Scholar 

  34. Berthelemy-Okazaki N, Zhao Y, Yang Z, Camp NJ, Farnham J, Parker D, et al. Examination of ELN as a candidate gene in the Utah intracranial aneurysm pedigrees. Stroke. 2005;36(6):1283–4.

    PubMed  CAS  Google Scholar 

  35. Mineharu Y, Inoue K, Inoue S, Yamada S, Nozaki K, Takenaka K, et al. Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm. Stroke. 2006;37(5):1189–94.

    PubMed  CAS  Google Scholar 

  36. Yamada S, Utsunomiya M, Inoue K, Nozaki K, Miyamoto S, Hashimoto N, et al. Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families. Stroke. 2003;34(4):892–900.

    PubMed  CAS  Google Scholar 

  37. Hofer A, Hermans M, Kubassek N, Sitzer M, Funke H, Stogbauer F, et al. Elastin polymorphism haplotype and intracranial aneurysms are not associated in Central Europe. Stroke. 2003;34(5):1207–11.

    PubMed  Google Scholar 

  38. McColgan P, Thant KZ, Sharma P. The genetics of sporadic ruptured and unruptured intracranial aneurysms: a genetic meta-analysis of 8 genes and 13 polymorphisms in approximately 20,000 individuals. J Neurosurg. 2010;112(4):714–21.

    PubMed  Google Scholar 

  39. Foroud T, Sauerbeck L, Brown R, Anderson C, Woo D, Kleindorfer D, et al. Genome screen to detect linkage to intracranial aneurysm susceptibility genes: the familial intracranial aneurysm (FIA) study. Stroke. 2008;39(5):1434–40.

    PubMed  CAS  Google Scholar 

  40. Brown Jr RD, Huston J, Hornung R, Foroud T, Kallmes DF, Kleindorfer D, et al. Screening for brain aneurysm in the familial intracranial aneurysm study: frequency and predictors of lesion detection. J Neurosurg. 2008;108(6):1132–8.

    PubMed  Google Scholar 

  41. Ronkainen A, Miettinen H, Karkola K, Papinaho S, Vanninen R, Puranen M, et al. Risk of harboring an unruptured intracranial aneurysm. Stroke. 1998;29(2):359–62.

    PubMed  CAS  Google Scholar 

  42. Bederson JB, Connolly Jr ES, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40(3):994–1025.

    PubMed  Google Scholar 

  43. Bor AS, Koffijberg H, Wermer MJ, Rinkel GJ. Optimal screening strategy for familial intracranial aneurysms: a cost-effectiveness analysis. Neurology. 2010;74(21):1671–9.

    PubMed  Google Scholar 

  44. Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, et al. Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med. 1992;327(13):916–20.

    PubMed  CAS  Google Scholar 

  45. Huston 3rd J, Torres VE, Sulivan PP, Offord KP, Wiebers DO. Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1993;3(12):1871–7.

    PubMed  Google Scholar 

  46. Saifuddin A, Dathan JR. Adult polycystic kidney disease and intracranial aneurysms. Br Med J (Clin Res Ed). 1987;295(6597):526.

    CAS  Google Scholar 

  47. Schievink WI. Marfan syndrome and intracranial aneurysms. Stroke. 1999;30(12):2767–8.

    PubMed  CAS  Google Scholar 

  48. Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders. A review. Stroke. 1994;25(4):889–903.

    PubMed  CAS  Google Scholar 

  49. Roman G, Fisher M, Perl DP, Poser CM. Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature. Ann Neurol. 1978;4(2):130–44.

    PubMed  CAS  Google Scholar 

  50. Schievink WI. Genetics and aneurysm formation. Neurosurg Clin N Am. 1998;9(3):485–95.

    PubMed  CAS  Google Scholar 

  51. Ho KL. Intraventricular aneurysm associated with tuberous sclerosis. Arch Neurol. 1980;37(6):385–6.

    PubMed  CAS  Google Scholar 

  52. Butler WE, Barker 2nd FG, Crowell RM. Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: a decision analysis. Neurosurgery. 1996;38(3):506–15; discussion 15–6.

    PubMed  CAS  Google Scholar 

  53. Giombini S, Morello G. Cavernous angiomas of the brain. Account of fourteen personal cases and review of the literature. Acta Neurochir (Wien). 1978;40(1–2):61–82.

    CAS  Google Scholar 

  54. Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, et al. Cerebral cavernous malformations. Incidence and familial occurrence. N Engl J Med. 1988;319(6):343–7.

    PubMed  CAS  Google Scholar 

  55. Al-Shahi R, Bhattacharya JJ, Currie DG, Papanastassiou V, Ritchie V, Roberts RC, et al. Prospective, population-based detection of intracranial vascular malformations in adults: the Scottish Intracranial Vascular Malformation Study (SIVMS). Stroke. 2003;34(5):1163–9.

    PubMed  Google Scholar 

  56. McCormick WF. The pathology of vascular (“arteriovenous”) malformations. J Neurosurg. 1966;24(4):807–16.

    PubMed  CAS  Google Scholar 

  57. Otten P, Pizzolato GP, Rilliet B, Berney J. 131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies. Neurochirurgie. 1989;35(2):128–31.

    Google Scholar 

  58. Kim DS, Park YG, Choi JU, Chung SS, Lee KC. An analysis of the natural history of cavernous malformations. Surg Neurol. 1997;48(1):9–17. discussion 17–8.

    PubMed  CAS  Google Scholar 

  59. Del Curling Jr O, Kelly Jr DL, Elster AD, Craven TE. An analysis of the natural history of cavernous angiomas. J Neurosurg. 1991;75(5):702–8.

    PubMed  Google Scholar 

  60. Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg. 1991;75(5):709–14.

    PubMed  CAS  Google Scholar 

  61. Sage MR, Brophy BP, Sweeney C, Phipps S, Perrett LV, Sandhu A, et al. Cavernous haemangiomas (angiomas) of the brain: clinically significant lesions. Australas Radiol. 1993;37(2):147–55.

    PubMed  CAS  Google Scholar 

  62. Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, et al. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg. 1994;80(3):422–32.

    PubMed  CAS  Google Scholar 

  63. Hayman LA, Evans RA, Ferrell RE, Fahr LM, Ostrow P, Riccardi VM. Familial cavernous angiomas: natural history and genetic study over a 5-year period. Am J Med Genet. 1982;11(2):147–60.

    PubMed  CAS  Google Scholar 

  64. Dashti SR, Hoffer A, Hu YC, Selman WR. Molecular genetics of familial cerebral cavernous malformations. Neurosurg Focus. 2006;21(1):e2.

    PubMed  Google Scholar 

  65. Maraire JN, Awad IA. Intracranial cavernous malformations: lesion behavior and management strategies. Neurosurgery. 1995;37(4):591–605.

    PubMed  CAS  Google Scholar 

  66. Tekkok IH, Ventureyra EC. De novo familial cavernous malformation presenting with hemorrhage 12.5 years after the initial hemorrhagic Ictus: natural history of an infantile form. Pediatr Neurosurg. 1996;25(3):151–5.

    PubMed  CAS  Google Scholar 

  67. Detwiler PW, Porter RW, Zabramski JM, Spetzler RF. De novo formation of a central nervous system cavernous malformation: implications for predicting risk of hemorrhage. Case report and review of the literature. J Neurosurg. 1997;87(4):629–32.

    PubMed  CAS  Google Scholar 

  68. Larson JJ, Ball WS, Bove KE, Crone KR, Tew Jr JM. Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg. 1998;88(1):51–6.

    PubMed  CAS  Google Scholar 

  69. Chang SD, Vanefsky MA, Havton LA, Silverberg GD. Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma. Neurol Res. 1998;20(6):529–32.

    PubMed  CAS  Google Scholar 

  70. Ogilvy CS, Moayeri N, Golden JA. Appearance of a cavernous hemangioma in the cerebral cortex after a biopsy of a deeper lesion. Neurosurgery. 1993;33(2):307–9; discussion 9.

    PubMed  CAS  Google Scholar 

  71. Ciricillo SF, Dillon WP, Fink ME, Edwards MS. Progression of multiple cryptic vascular malformations associated with anomalous venous drainage. Case report. J Neurosurg. 1994;81(3):477–81.

    PubMed  CAS  Google Scholar 

  72. Dubovsky J, Zabramski JM, Kurth J, Spetzler RF, Rich SS, Orr HT, et al. A gene responsible for cavernous malformations of the brain maps to chromosome 7q. Hum Mol Genet. 1995;4(3):453–8.

    PubMed  CAS  Google Scholar 

  73. Craig HD, Gunel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, et al. Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15–13 and 3q25.2–27. Hum Mol Genet. 1998;7(12):1851–8.

    PubMed  CAS  Google Scholar 

  74. Gunel M, Awad IA, Anson J, Lifton RP. Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. Proc Natl Acad Sci USA. 1995;92(14):6620–4.

    PubMed  CAS  Google Scholar 

  75. Mindea SA, Yang BP, Shenkar R, Bendok B, Batjer HH, Awad IA. Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus. 2006;21(1):e1.

    PubMed  Google Scholar 

  76. Revencu N, Vikkula M. Cerebral cavernous malformation: new molecular and clinical insights. J Med Genet. 2006;43(9):716–21.

    PubMed  CAS  Google Scholar 

  77. Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, et al. Deletions in CCM2 are a common cause of cerebral cavernous malformations. Am J Hum Genet. 2007;80(1):69–75.

    PubMed  CAS  Google Scholar 

  78. Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, et al. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol. 2006;60(5):550–6.

    PubMed  Google Scholar 

  79. Chen L, Tanriover G, Yano H, Friedlander R, Louvi A, Gunel M. Apoptotic functions of PDCD10/CCM3, the gene mutated in cerebral cavernous malformation 3. Stroke. 2009;40(4):1474–81.

    PubMed  Google Scholar 

  80. Schleider E, Stahl S, Wustehube J, Walter U, Fischer A, Felbor U. Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3. Neurogenetics. 2011;12(1):83–6.

    PubMed  CAS  Google Scholar 

  81. Zhu Y, Wu Q, Xu JF, Miller D, Sandalcioglu IE, Zhang JM, et al. Differential angiogenesis function of CCM2 and CCM3 in cerebral cavernous malformations. Neurosurg Focus. 2010;29(3):E1.

    PubMed  Google Scholar 

  82. Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA. KRIT1 Association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis. Hum Mol Genet. 2002;11(4):389–96.

    PubMed  CAS  Google Scholar 

  83. Zhang J, Rigamonti D, Dietz HC, Clatterbuck RE. Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations. Neurosurgery. 2007;60(2):353–9; discussion 9.

    PubMed  Google Scholar 

  84. D’Angelo R, Marini V, Rinaldi C, Origone P, Dorcaratto A, Avolio M, et al. Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. Brain Pathol. 2011;21(2):215–24.

    PubMed  Google Scholar 

  85. Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol. 2007;6(3):237–44.

    PubMed  CAS  Google Scholar 

  86. Furlan AJ, Whisnant JP, Elveback LR. The decreasing incidence of primary intracerebral hemorrhage: a population study. Ann Neurol. 1979;5(4):367–73.

    PubMed  CAS  Google Scholar 

  87. Perret G, Nishioka H. Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage. IV. Cerebral angiography. An analysis of the diagnostic value and complications of carotid and vertebral angiography in 5,484 patients. J Neurosurg. 1966;25(1):98–114.

    PubMed  CAS  Google Scholar 

  88. Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet. 2002;359(9309):863–73.

    PubMed  Google Scholar 

  89. Berman MF, Sciacca RR, Pile-Spellman J, Stapf C, Connolly Jr ES, Mohr JP, et al. The epidemiology of brain arteriovenous malformations. Neurosurgery. 2000;47(2):389–96; discussion 97.

    PubMed  CAS  Google Scholar 

  90. Stapf C, Mast H, Sciacca RR, Berenstein A, Nelson PK, Gobin YP, et al. The New York Islands AVM Study: design, study progress, and initial results. Stroke. 2003;34(5):e29–33.

    PubMed  CAS  Google Scholar 

  91. ApSimon HT, Reef H, Phadke RV, Popovic EA. A population-based study of brain arteriovenous malformation: long-term treatment outcomes. Stroke. 2002;33(12):2794–800.

    PubMed  CAS  Google Scholar 

  92. Hofmeister C, Stapf C, Hartmann A, Sciacca RR, Mansmann U, TerBrugge K, et al. Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation. Stroke. 2000;31(6):1307–10.

    PubMed  CAS  Google Scholar 

  93. Padget DH. The cranial venous system in man in reference to development, adult configuration, and relation to the arteries. Am J Anat. 1956;98(3):307–55.

    PubMed  CAS  Google Scholar 

  94. Stein BM, Wolpert SM. Arteriovenous malformations of the brain. I: current concepts and treatment. Arch Neurol. 1980;37(1):1–5.

    PubMed  CAS  Google Scholar 

  95. Mullan S, Mojtahedi S, Johnson DL, Macdonald RL. Embryological basis of some aspects of cerebral vascular fistulas and malformations. J Neurosurg. 1996;85(1):1–8.

    PubMed  CAS  Google Scholar 

  96. Gonzalez LF, Bristol RE, Porter RW, Spetzler RF. De novo presentation of an arteriovenous malformation. Case report and review of the literature. J Neurosurg. 2005;102(4):726–9.

    PubMed  Google Scholar 

  97. Kader A, Goodrich JT, Sonstein WJ, Stein BM, Carmel PW, Michelsen WJ. Recurrent cerebral arteriovenous malformations after negative postoperative angiograms. J Neurosurg. 1996;85(1):14–8.

    PubMed  CAS  Google Scholar 

  98. Lasjaunias P. A revised concept of the congenital nature of cerebral arteriovenous malformations. Interv Neuroradiol. 1997;3(4):275–81.

    PubMed  CAS  Google Scholar 

  99. Deshpande DH, Vidyasagar C. Histology of the persistent embryonic veins in arteriovenous malformations of brain. Acta Neurochir (Wien). 1980;53(3–4):227–36.

    CAS  Google Scholar 

  100. Nussbaum ES, Heros RC, Madison MT, Awasthi D, Truwit CL. The pathogenesis of arteriovenous malformations: insights provided by a case of multiple arteriovenous malformations developing in relation to a developmental venous anomaly. Neurosurgery. 1998;43(2):347–51; discussion 51–2.

    PubMed  CAS  Google Scholar 

  101. Leblanc R, Melanson D, Wilkinson RD. Hereditary neurocutaneous angiomatosis. Report of four cases. J Neurosurg. 1996;85(6):1135–42.

    PubMed  CAS  Google Scholar 

  102. Yokoyama K, Asano Y, Murakawa T, Takada M, Ando T, Sakai N, et al. Familial occurrence of arteriovenous malformation of the brain. J Neurosurg. 1991;74(4):585–9.

    PubMed  CAS  Google Scholar 

  103. van Beijnum J, van der Worp HB, Schippers HM, van Nieuwenhuizen O, Kappelle LJ, Rinkel GJ, et al. Familial occurrence of brain arteriovenous malformations: a systematic review. J Neurol Neurosurg Psychiatry. 2007;78(11):1213–7.

    PubMed  Google Scholar 

  104. Inoue S, Liu W, Inoue K, Mineharu Y, Takenaka K, Yamakawa H, et al. Combination of linkage and association studies for brain arteriovenous malformation. Stroke. 2007;38(4):1368–70.

    PubMed  Google Scholar 

  105. Snead 3rd OC, Acker JD, Morawetz R. Familial arteriovenous malformation. Ann Neurol. 1979;5(6):585–7.

    PubMed  Google Scholar 

  106. Boyd MC, Steinbok P, Paty DW. Familial arteriovenous malformations. Report of four cases in one family. J Neurosurg. 1985;62(4):597–9.

    PubMed  CAS  Google Scholar 

  107. Brilli RJ, Sacchetti A, Neff S. Familial arteriovenous malformations in children. Pediatr Emerg Care. 1995;11(6):376–8.

    PubMed  CAS  Google Scholar 

  108. Pawlikowska L, Tran MN, Achrol AS, Ha C, Burchard E, Choudhry S, et al. Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations. Stroke. 2005;36(10):2278–80.

    PubMed  CAS  Google Scholar 

  109. Hashimoto T, Lawton MT, Wen G, Yang GY, Chaly Jr T, Stewart CL, et al. Gene microarray analysis of human brain arteriovenous malformations. Neurosurgery. 2004;54(2):410–23; discussion 23–5.

    PubMed  Google Scholar 

  110. Young WL, Yang GY. Are there genetic influences on sporadic brain arteriovenous malformations? Stroke. 2004;35(11 Suppl 1):2740–5.

    PubMed  Google Scholar 

  111. Shenkar R, Elliott JP, Diener K, Gault J, Hu LJ, Cohrs RJ, et al. Differential gene expression in human cerebrovascular malformations. Neurosurgery. 2003;52(2):465–77; discussion 77–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer E. Fugate DO .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Fugate, J.E., Brown, R.D. (2013). The Genetics of Cerebral Aneurysms and Other Vascular Malformations. In: Sharma, P., Meschia, J. (eds) Stroke Genetics. Springer, London. https://doi.org/10.1007/978-0-85729-209-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-209-4_4

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-208-7

  • Online ISBN: 978-0-85729-209-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics