**2. Etiology**

Ten to fifteen percent of moyamoya disease (MMD) is familial in origin which indicates a genetic association. East Asian populations with RNF213 gene on chromosome

17q25.3 are susceptible to MMD [4]. In another report from Japan, it was observed that a variant of RNF213 (c.14576G) was present in 41 patients with familial MMD (95%), 163 patients with sporadic MMD (79%), and 283 normal control subjects (2%) [5]. In a study in Chinese Han population, Wu et al. demonstrated that mutations in RNF213 gene were associated with increased susceptibility to MMD. In further analysis, they observed that ischemic MMD was related to the R4810K mutation, and hemorrhagic MMD was associated with the A4399T mutation [6]. Mineharu et al. suggested that MMD is an autosomal dominant disease with incomplete penetrance [7]. Inoue et al. observed that different alleles of genes of HLA antigen have been found to be associated with MMD [8]. Several inducers of angiogenesis such as fibroblast growth factor, transforming growth factor beta1, and hepatocyte growth factor which promote neovascularization were found in high levels in patients with MMD [9–11].

Moyamoya syndrome (MMS) is a different entity when the disease is associated with some other conditions such as [12]:


There are reports of identical twins with only one among them affected by MMD, which question the genetic basis and focus on environmental factors for the condition [13].
