Early onset of moyamoya syndrome in a Down syndrome patient with the genetic variant RNF213 p.R4810K

Abstract

Moyamoya syndrome is a unique progressive occlusive cerebrovascular disease that predisposes affected patients to stroke. We describe the case of a 2-year-old girl presenting with early onset of moyamoya syndrome with concurrent Down syndrome. Genetic testing revealed a heterozygous missense variant of RNF213. RNF213 was recently identified as the first susceptibility gene for moyamoya disease in patients with no known associated risk factors. The reported median age at the onset of idiopathic moyamoya disease with a heterozygous RNF213 risk variant is 7 years, while, the average age at onset of moyamoya syndrome in Down syndrome is 7-16 years. Down syndrome and RNF213 variant contribute to the development of moyamoya vasculopathy in different ways. Although the underlying mechanism is not fully understood, an additive effect was observed with the early-onset seen in this patient. Little is known about the potential association between RNF213 and moyamoya syndrome. Based on these observations, we hypothesize that the RNF213 risk variant has a modifier effect in steno-occlusive vasculopathy, even in medical conditions known to be associated with moyamoya syndrome.

Keywords: Down syndrome; Moyamoya syndrome; Pediatric stroke; RNF213.