Molecular Genetics of Ischaemic Stroke


Rare examples of single gene disorders have been described for all major subtypes of ischaemic stroke; accelerated atherosclerosis and subsequent thrombo‐embolism (e.g. homocysteinuria), connective tissue disease resulting in arterial dissections (e.g. Ehler‐Danlos type IV), disorders of cerebral small vessels (e.g. CADASIL), cardiac embolism (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. MELAS) and coagulopathies (e.g. sickle cell disease).

Although animal models, family history and twin studies suggest that hereditary factors might contribute to the risk of sporadic stroke, no single gene has so far been conclusively shown to do so. It is unlikely that the direct genetic contribution of any single gene towards stroke is more than modest and it is likely that the effects are mainly mediated through genetic influences on risk factors and intermediate phenotypes. Single genes are unlikely to be helpful for any risk stratification in clinical practice.

Key Concepts:

  • Rare examples of single gene disorders have been described for all major subtypes of ischaemic stroke.

  • Although animal models, family history and twin studies suggest that hereditary factors might contribute to the risk of sporadic stroke, no single gene has so far been conclusively shown to do so.

  • It is unlikely that the direct genetic contribution of any single gene towards stroke is more than modest.

  • It is likely that genetic effects are mainly mediated through genetic influences on risk factors and intermediate phenotypes.

  • Single genes are unlikely to be helpful for any risk stratification in clinical practice.

Keywords: ischaemic stroke; genes; family history; heritability; CADASIL; MELAS; hypertension; atherosclerosis; leukoaraiosis

Figure 1.

MR images (axial short T1 inversion recovery, coronal flair, axial gradient ECHO sequences) obtained in a 54‐year‐old man with a NOTCH3 mutation showing extensive signal change within the cerebral hemispheres including bilateral involvement of the anterior temporal lobes. There are numerous lacunes within the basal ganglia and associated microhaemorrhages diffusely throughout both cerebral hemispheres. Courtesy of Dr Geraldine Quaghebeur, Department of Neuroradiology, John Radcliffe Hospital Oxford.

Figure 2.

CT and MR images (coronal T2‐weighted) obtained in a 40‐year‐old man who presented with sudden onset expressive and receptive dysphasia and grand mal seizures. The CT shows bilateral basal ganglia calcification and hypodensity in the left temporal lobe. The MRI shows a mainly cortical hyperintensity in the left temporo‐parietal region, not typical of a middle cerebral artery branch infarction. These images are characteristic for patients with MELAS. Reproduced from Pendlebury SA, Anslow P and Rothwell PM (2007) Neurological Case Histories, p. 101 (Figs. 17.1 and 17.2). Oxford: Oxford University Press. With permission from Oxford University Press.



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Further Reading

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Floßmann, Enrico(Apr 2010) Molecular Genetics of Ischaemic Stroke. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022411]