Introduction: Moyamoya disease (MMD) is a rare idiopathic cerebrovascular disorder characterized by progressive stenosis of the internal carotid arteries (ICA) leading to ischemic or hemorraghic events.  Due to higher incidence of familial occurrence in East Asian populations (Japanese, Korean and Chinese), RNF213 has most recently been identified as a MMD susceptibility gene with the c.14576G>A variant mutation being associated with the highest risk of MMD with odds ratio >250 . However, there appears to be a gradient prevalence of this variant even amongst East Asians (> 79% in Japanese and Koreans, only 23% in Chinese), but thus far, no reported linkage in Southeast Asians or Caucausians has been reported. The dosage of the c.14576G>A variant mutation has been purported to predict the severity of clinical phenotype homozygotes having early onset and aggressive disease course presenting before age 4-years with ischemic stroke.

Case Description: We report a South Asian (Bangladeshi) non-consanguinous family with both parents having confirmed heterozygous c.14576G>A polymorphism of RNF213, and all 3 children having homozygous mutations of the same variant. Two of the 3 children presented with ischemic stroke and confirmed MMD at age 5 and 14 years. The youngest child (currently 7 years) is asymptomatic  but has suspicious unilateral focal narrowing of the right ICA that could portend early MMD. Both parents in their 40s have reported TIA-like events, but no MMD on neuroimaging. This is the first report of siblings and parents of South Asian descent with confirmed RNF213 variant mutations of different doses.

Conclusions: RNF 213 gene mutation may be more prevalent in MMD in other ethnic groups also in addition to East Asians and testing is merited, particularly in familial cases.