Development of atherosclerotic-moyamoya syndrome with genetic variant of RNF213 p.R4810K and p.T1727M: A case report

Objective: We report a rare case of atherosclerotic-moyamoya syndrome (A-MMS) in an adult female with genetic variant of both ring finger 213 (RNF213) p.R4810K and p.T1727M.

Case report: A 46-year-old previously healthy, right-handed woman displayed transient slurred speech, which started to worsen four years ago. Initial magnetic resonance angiography (MRA) revealed stenosis in left middle cerebral artery (MCA), bilateral anterior cerebral artery (ACA), and left posterior cerebral artery (PCA). The patient subsequently underwent catheter angiography, which confirmed the formation of moyamoya vessels, with Suzuki's angiographic staging of grade-3 on the left side. Although the patient had been on both anti-platelet and statin therapy at the time, a follow-up examination showed further exacerbation of left MCA stenosis, along with enhanced moyamoya vessel formation. On black-blood imaging using DANTE-SPACE, there were eccentric, evolving lesions in the left MCA. We next screened for potential genetic variants, using genomic DNA samples isolated from both the patient and her immediate family members. The results showed that the patient, along with her mother, sister, and brother, possessed the heterozygous variant of the RNF213 gene, including c.14429G > A (p.R4810K) and c.5180C > T (p.T1727M). The patient's daughter did not have the variant.

Conclusion: Collectively, we present a unique case of A-MMS with genetic variant of RNF213 p.R4810K and p.T1727M, manifesting as progression. Based on the family tree, these two mutations are on the same RNF213 haplotype. Whether atherosclerosis is the cause of A-MMS or it further exacerbates the injury of MMD to the A-MMS patients with RNF213 gene variant is a question to be investigated.