OBJECT: Moyamoya disease (MMD) is a rare cerebrovascular disorder involving 
stenosis of the major vessels of the circle of Willis and proximal portions of 
its principal branches. Despite concerted investigation, the pathophysiology of 
the disorder has not been fully elucidated. Currently, the major proteins 
believed to play an active role in the pathogenesis include vascular endothelial 
growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth 
factor (HGF), transforming growth factor-β₁ (TGFβ₁), and granulocyte 
colony-stimulating factor (G-CSF). In terms of the genetics, recent literature 
suggests a low penetrance autosomal dominant or polygenic mode of transmission 
involving chromosomes 3, 6, 8, 12, and 17 for familial MMD. This review 
summarizes the current knowledge on the histopathology, pathophysiology and 
genetics of MMD.
METHODS: A PubMed/Medline systematic study of the literature was performed, from 
which 45 articles regarding MMD pathophysiology were identified and analyzed.
CONCLUSIONS: Moyamoya disease is characterized by the intimal thickening and 
media attenuation of the proximal vessels of the circle of Willis as well as the 
development of an aberrant distal vascular network. The primary proteins that 
are currently implicated in the pathophysiology of MMD include VEGF, bFGF, HGF, 
TGFβ₁, and G-CSF. Furthermore, the current literature on familial MMD has 
pointed to a low penetrance autosomal dominant or polygenic mode of 
transmittance at loci on chromosomes 3, 6, 8, 12, and 17.