What Causes Moyamoya Disease? Exploring Genetic, Environmental, and Regional Factors
Moyamoya disease is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of arteries in the brain, leading to the formation of fragile collateral blood vessels that resemble a "puff of smoke" on imaging—hence the name, which means "puff of smoke" in Japanese. Despite ongoing research, the exact cause of moyamoya disease remains unclear. However, scientific studies suggest it may develop due to a combination of genetic predisposition and acquired (environmental or health-related) factors.
Genetic and Congenital Influences in Moyamoya Disease
Evidence indicates that congenital or hereditary factors play a significant role, especially in pediatric cases diagnosed before the age of 10. Researchers have identified certain gene mutations, such as those in the RNF213 gene, that are strongly associated with familial forms of the disease, particularly in East Asian populations. In these early-onset cases, abnormal vascular development may begin in utero or during early childhood, suggesting a strong genetic component. Children with a family history of moyamoya or other cerebrovascular conditions may be at higher risk, emphasizing the importance of genetic screening in high-risk groups.
Acquired Triggers and Underlying Health Conditions
On the other hand, acquired or secondary forms of moyamoya syndrome often occur in individuals without a clear genetic link. These cases may be triggered by various medical conditions, including chronic infections like middle ear infections (otitis media) or cerebral venous sinus thrombosis. Autoimmune disorders such as systemic lupus erythematosus (SLE), thyroiditis, and sickle cell disease have also been linked to the development of moyamoya-like vascular changes. In these instances, inflammation and immune system dysfunction may contribute to arterial damage and subsequent vessel narrowing.
Regional and Geographic Patterns in Incidence
Notably, there are distinct geographic and regional variations in the prevalence of moyamoya disease. Countries like Japan, Korea, and China report significantly higher incidence rates, but within China, certain provinces such as Jiangxi and Henan also show elevated numbers of cases. This clustering suggests that environmental or lifestyle factors—possibly combined with localized genetic traits—may influence disease development. Public health researchers are investigating whether regional differences in diet, pollution levels, or viral exposure could contribute to these patterns.
Environmental and Climatic Considerations
While not yet fully proven, emerging data hints at a potential connection between climate, air quality, and vascular health. Some studies propose that prolonged exposure to cold climates or high-altitude environments might increase hemodynamic stress on cerebral blood vessels, potentially accelerating the progression of moyamoya in susceptible individuals. Additionally, long-term exposure to air pollutants and industrial toxins could promote chronic inflammation and endothelial dysfunction—both of which are implicated in cerebrovascular diseases.
Ongoing Research and Future Directions
Despite advances in neuroimaging and genetics, many questions about moyamoya disease remain unanswered. Scientists continue to explore the interplay between genetic susceptibility, immune response, and environmental triggers to better understand how and why the disease develops. Large-scale epidemiological studies, especially those comparing high-incidence and low-incidence regions, are crucial for identifying modifiable risk factors and improving prevention strategies. As awareness grows and diagnostic tools improve, earlier detection and targeted therapies may significantly enhance outcomes for patients worldwide.