INTRODUCTION: While a plethora of studies exist exploring the diverse components of MMD, a multifaceted approach is needed to target new therapeutic interventions and provide a holistic understanding of the genetic and inflammatory components of MMD etiology. METHODS: A literature review was conducted using PubMed, Embase, and the Cochrane Library, ranging from genetic predispositions in specific populations, the p.R4810K variant in the RNF213 gene, animal models, other genetic variants, and inflammatory pathways such as cytokines and biomarkers. The search encompassed studies up to January 2024. The inclusion criteria for this review were peer-reviewed articles on MMD, and the exclusion criteria were studies that were only reviews without direct statistical data on the genetic and inflammatory markers. The keywords included "Moyamoya Disease genetics," "inflammatory markers," "Moyamoya Disease," and "RNF213 gene". RESULTS: With over 30 studies having met the inclusion criteria, including over 1500 patients, MMD is expressed in the Asian descent populations via the RNF213 gene. Focusing specifically on the p.R4810K variant in East Asian populations, this mutation was found to be responsible for improper blood vessel development, maintenance, and homeostasis in the constriction of MMD blood vessels. Using Zebrafish and Murine models, a correlation was made between zebrafish and the p.R4810K gene; in murine models, ACTA2 and NEO1 genes were revealed to produce different changes in MMD rather than the RNF213 gene. Other genetic variants, including the Human Leukocyte Antigen (HLA) system and Smooth Muscle Cells (SMC), have offered a multidimensional complexity behind the disease. DISCUSSION: The interconnected nature of MMD genetics and inflammation provides a new perspective on treatment methodology. While the RNF213 gene, particularly the p.R4810K variant, plays a crucial role in MMD susceptibility within the East Asian community, the disease is not solely limited to its genetic factors. CONCLUSION: New research must emphasize a multimodal treatment plan to stay on pace with the ever-evolving genetic and inflammatory mechanisms of the pathology.
Kashibhatla et al. (Mon,) studied this question.