Progress Review The Genetics of Cervical Artery Dissection A Systematic Review

Background and Purpose—The pathophysiology of cervical artery dissections (CAD), a major cause of ischemic stroke in young adults, is poorly understood. Several arguments suggest a genetic predisposition. Methods—We systematically reviewed all published data on genetic risk factors for CAD and performed a meta-analysis of association studies with the MTHFR C677T polymorphism. Results—Rarely, CAD is associated with a known monogenic connective tissue disease, mainly vascular Ehlers-Danlos syndrome. However, in the large majority of CAD cases, there is no evidence for a known monogenic disease. Several arguments, including the association of CAD with dermal connective tissue abnormalities that are inherited, suggest that genetic factors also play a role in “sporadic ” CAD as part of a multifactorial predisposition. We identified 15 genetic association studies: 10 were negative and 5 reported associations of 3 genetic variants in 3 different candidate genes. Two studies reported associations with polymorphisms in ICAM-1 and COL3A1, but neither has been replicated. Three studies reported an association with the MTHFR 677TT genotype, but 3 other studies did not replicate this. A meta-analysis of these data identified an overall significant association of the MTHFR 677TT genotype with CAD (OR, 1.67; 95 % CI, 1.21 to 2.31). We also identified 9 studies screening candidate genes for mutations and 4 linkage studies, yielding mostly negative results. Conclusions—Although several interesting hypotheses were generated, the majority of genetic studies in CAD have bee