Two Postmortem Cases of Moyamoya Disease with Different RNF213 p.R4810K Variant Statuses

Moyamoya disease (MMD) is characterized by distinct histopathological changes in intracranial arteries, such as narrowing of the arterial lumen due to thickening of the tunica intima, waving of the internal elastic membranes, and thinning of the tunica media. Ring finger protein 213 <i>(RNF213)</i> is a susceptibility gene for MMD that affects clinical outcomes. However, little is known about its relationship with histopathology. Herein, we present the postmortem histopathological evaluation of 2 MMD cases with and without <i>RNF213</i> p.R4810K variant. The first patient was a 39-year-old female, with a history of undergoing bilateral indirect revascularization at the age of 10 years, who died from brainstem ischemic stroke. The second patient was a 32-year-old female who was conservatively treated from the age of 14 years but died from intraventricular hemorrhage. Postmortem analysis revealed that the first patient had a homozygous variant, whereas the second patient lacked this variant. Both cases exhibited similar advanced stages of MMD with posterior artery involvement on magnetic resonance angiography. However, compared with the second patient without the <i>RNF213</i> p.R4810K variant, the first patient with this homozygous variant showed more prominent histopathological changes, such as narrowing of the arterial lumen due to thickening of the tunica intima, waving of the internal elastic membranes, and thinning of the tunica media. Although an accumulation of cases is required to draw a definite conclusion, these cases suggest that <i>RNF213</i> p.R4810K variant status may affect the vascular histopathology of MMD and its clinical outcome.