Genetics of Cervical Artery Dissection

Cervical artery dissection (CeAD), relatively uncommon in the general population, is a major cause of ischemic stroke in young and middle-aged adults. Its risk factors and underlying mechanisms are poorly understood. Seldom, CeAD can be caused by a monogenic connective tissue disease. In the absence of such a disorder, <3% of CeAD patients have a family history of symptomatic CeAD, and in some series about half of CeAD patients were shown to have skin connective tissue abnormalities segregating in families according to an autosomal dominant pattern. In most CeAD cases, converging evidence suggests that genetic factors might play a role as part of a multifactorial predisposition. Several candidate gene association studies have been published, on relatively small samples, and have failed to reveal any robust associations. The first genome-wide association study (GWAS) of CeAD, resulting from a large international effort gathering samples from over 2000 CeAD patients, identified a common intronic variant in PHACTR1 to be significantly associated with CeAD risk. Interestingly, the same variant has also shown association with migraine, fibromuscular dysplasia, coronary artery dissection, hypertension, coronary calcification and coronary artery disease, with effects in the opposite direction for the latter two. GWAS of these and other conditions have also provided broader insight into shared genetic variants and biological pathways underlying these vasculopathies. Additional studies on larger samples, including the analysis of rare variants, are required to further reveal the genetic underpinnings of CeAD.