Nirali Vora, MD

Miyawaki S, Imai H, Shimizu M, Yagi S, Ono H, Mukasa H, et al. Genetic Variant RNF213 c.14576G>A in Various Phenotypes ofIntracranial Major Artery Stenosis/Occlusion. Stroke. 2013


I always thought bad intracranial artery stenosis/occlusion (ICASO) in East Asian folks was from modifiable atherosclerosis and felt any label of a genetic “moya-moya” was incorrect. Was I wrong? 

This Japanese group looked at a previously identified ring finger protein gene variant, “RNF213c.14576G>A,” which has been associated with moya-moya in East Asians. In this case control study, they confirm the strong genetic association to definite, bilateral moya-moya (OR 144) > unilateral moya-moya (OR 54) > ICASO (OR 16.8) and no association in the control group or patients with extracranial athero, aneurysms, or ICH.

Makes you wonder if ICASO is on a spectrum with moya moya disease. The variant’s biochemical function is presently unknown, but could provide a clue regarding pathogenesis of vessel disease common in this population. 

While I won’t be rushing to an EC-IC bypass if the variant shows up on my 23andme report, I would be very aggressive with vascular risk reduction and have a higher threshold for vessel imaging in East Asians.