Impact of RNF213 Variant Status on Revascularization Surgery for Moyamoya Disease: Implications for Precision Medicine

Abstract

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease which is characterized by the progressive stenosis at the internal carotid artery terminus and abnormal vascular network formation at the base of the brain. Although its etiology is still unknown, increasing evidence suggest the importance of the characteristic genetic variant of RNF213 p.R4810K polymorphism in its clinical presentation such as the early onset-age and/or clinical severity of MMD. More recently, MMD patients with RNF213 variant are shown to develop more neovascular pial synangiosis derived from encephalo-myo-synangiosis after combined revascularization surgery compared to non-variant patients, either in children or in adults. Alternatively, MMD patients with RNF213 variant are known to have potentially higher risk for delayed/prolonged cerebral hyperperfusion after combined revascularization surgery. The exact mechanism underlying such characteristic postoperative pathophysiology in RNF213 variant patients is undetermined, while modern high resolution magnetic resonance imaging vessel wall imaging studies may give clues to this mechanism by exploring the enhanced negative remodeling (medial layer thinness and outer diameter narrowing) of the intracranial arteries in MMD patients with RNF213 variant.