Genetic testing for Mendelian stroke due to cerebrovascular anomalies and other syndromes

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Abstract

Stroke is defined as a focal or at times global neurological impairment of sudden onset and presumed vascular origin. 85% of strokes are due to cerebral ischemia and the other 15% to primary intracerebral hemorrhage.

Ischemic stroke (IS) is characterized by complete or partial obstruction of a vessel in the brain, resulting in lack of blood supply and death of brain tissue. The most common causes of IS are atherosclerosis, cardioembolism and small-vessel disease (lacunar stroke). Genetic factors play important role. Incidence rates for IS in the 15- to 45-year age range are ≈10 per 100,000 person years.

Hemorrhagic stroke (HS) is the least treatable and the most fatal form of cerebrovascular disease. Genetic mechanisms play a role in its development. Occurrence depends on many risk factors, including hypertension, heavy alcohol intake and anticoagulant treatment. According to the World Health Organization, 15 million people suffer stroke worldwide each year. The overall incidence of spontaneous HS worldwide is 24.6 per 100,000 person years. Strokes are the third most common cause of death and the most common cause of disability in developed countries.

This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

1. WHO MONICA Project Investigators The World Health Organization MONICA Project (Monitoring trends and determinants in cardiovascular disease). J Clin Epidemiol. 1988; 41(2): 105-14.

2. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24(1): 35-41.

3. Philip M, Bath W, Lees KR. ABC of arterial and venous disease. BMJ. 2000; 320: 920–23.

4. Brass LM, Isaacsohn JL, Merikangas KR, Robinette CD. A study of twins and stroke. Stroke. 1992; 23(2): 221-23.

5. Markus HS. Unravelling the Genetics of Ischaemic Stroke. PLoS Medicine. 2010; 7(3): e1000225.

6. Tonk M, Haan J. A review of genetic causes of ischemic and hemorrhagic stroke. J Neurol Sci. 2007; 257(1-2): 273-79.

7. Kittner SJ, McCarter RJ, Sherwin RW, Sloan MA, Stern BJ, Johnson CJ, Buchholz D, Seipp MJ, Price TR. Black-white differences in stroke risk among young adults. Stroke. 1993; 24(12 Supp1): I13–I15.

8. Harmsen P, Wilhelmsen L, Jacobsson A. Stroke incidence and mortality rates 1987 to 2006 related to secular trends of cardiovascular risk factors in Gothenburg, Sweden. Stroke. 2009; 40(8): 2691–2697.

9. Rannikmäe K, Sivakumaran V, Millar H, Malik R, Anderson CD, Chong M, Dave T, Falcone GJ, Fernandez-Cadenas I, Jimenez-Conde J, Lindgren A, Montaner J, O’Donnell M, Paré G, Radmanesh F, Rost NS, Slowik A, Söderholm M, Traylor M, Pulit SL, Seshadri S, Worrall BB, Woo D, Markus HS, Mitchell BD, Dichgans M, Rosand J, Sudlow CLM. Stroke Genetics Network (SiGN), METASTROKE Collaboration, and International Stroke Genetics Consortium (ISGC). COL4A2 is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls. Neurology. 2017; 89(17): 1829-39.

10. Thiele H, du Moulin M, Barczyk K, George C, Schwindt W, Nürnberg G, Frosch M, Kurlemann G, Roth J, Nürnberg P, Rutsch F. Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. Hum Mutat. 2010; 31(11): E1836-50.

11. Rost NS, Greenberg SM, Rosand J. The genetic architecture of intracerebral hemorrhage. Stroke. 2008; 39(7): 2166-73.

12. Tonk M, Haan J. A review of genetic causes of ischemic and hemorrhagic stroke. J Neurol Sci. 2007; 257(1-2): 273-79.

13. Liebeskind D. Hemorrhagic Stroke. Updated: Jan 23, 2017 by WebMD LLC. available from: https://emedicine.medscape.com/article/1916662-overview#a5.

14. Global Burden of Stroke. The atlas of Heart Disease and Stroke. MacKay J, Mensah GA. World Health Organization. Available from: http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf

15. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010; 9(2): 167-76.

16. Aguilar MI, Freeman WD. Spontaneous intracerebral hemorrhage. Semin Neurol 2010; 30(5): 555–64.

17. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, Mayberg M, Morgenstern L, Ogilvy CS, Vespa P, Zuccarello M. American Heart Association; American Stroke Association Stroke Council; High Blood Pressure Research Council; Quality of Care and Outcomes in Research Interdisciplinary Working Group. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007; 116(6): e391-13.

18. Elliott J, Smith M. The Acute Management of Intracerebral Hemorrhage: A Clinical Review. Anesthesia & Analgesia. 2010; 110(5): 1419–27.

19. Smith SD, Eskey CJ. Hemorrhagic stroke. Radiol Clin North Am. 2011; 49(1): 27-45.

20. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J; INTERACT Investigators. INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008; 7(5): 391-99

21. Falcone GJ, Woo D. Genetics of Spontaneous Intracerebral Hemorrhage. Stroke. 2017; 48(12): 3420-24.

22. French CR, Seshadri S, Destefano AL, Fornage M, Arnold CR, Gage PJ, Skarie JM, Dobyns WB, Millen KJ, Liu T, Dietz W, Kume T, Hofker M, Emery DJ, Childs SJ, Waskiewicz AJ, Lehmann OJ. Mutation of FOXC1 and PITX2 induces cerebra small-vessel disease. J Clin Invest. 2014; 124(11): 4877-81.

23. Chen B, Gagnon M, Shahangian S, Anderson NL, Howerton DA, Boone JD; Centers for Disease Control and Prevention (CDC). Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions. MMWR Recomm Rep 2009; 58(RR-6): 1-37.

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