RNF213 Variants Associated With Periventricular Anastomosis Regression After Revascularization in Moyamoya Disease.

AIMS: This study aimed to investigate the characteristics, predictors, and clinical significance of periventricular anastomosis (PA) regression following revascularization in moyamoya disease (MMD).

METHODS

We conducted a longitudinal cohort study involving patients with MMD treated at our hospital between 2019 and 2023. Demographic, radiological findings, and clinical outcomes were recorded. C-terminal region of ring finger protein 213 (RNF213) was sequenced. Additionally, structural changes of the RNF213 variants were evaluated using a three-dimensional model of the human RNF213 protein.

RESULTS

Of 305 eligible patients, 103 experienced postoperative PA regression. Among the subtypes of PA, those derived from the lenticulostriate, anterior choroidal, and thalamotuberal arteries exhibited significant regression. Multivariate analysis identified age (p = 0.030), Suzuki stage (III-IV) (p = 0.043), preoperative PA score (p < 0.001), RNF213 p.R4810K variant (p = 0.019), other RNF213 rare variants (p = 0.004), and postoperative Matsushima grading (p < 0.001) were associated with postoperative PA regression. The risk of future hemorrhage was significantly higher in the non-PA regression group (p = 0.040). 80% of rare variants without structural changes did not exhibit PA regression.

CONCLUSIONS

RNF213 variants in the C-terminal region are associated with PA regression, underscoring a broader genotype-phenotype correlation. Furthermore, PA regression might be considered a potential radiological marker to predict the risk of future hemorrhage in MMD patients.