Atypical moyamoya vessels forming plexiform vascular networks similar to the twig-like middle cerebral artery in a pediatric patient with Neurofibromatosis type 1 associated moyamoya syndrome

Abstract

A 4-year-old girl was referred to our institute for recurrent transient left-sided weakness and abnormal findings on magnetic resonance angiography. She had a family history of neurofibromatosis type 1 (NF1) and multiple pigmented skin lesions from the birth. Cerebral angiography showed severe stenosis of the terminal portions of the right internal carotid artery and abnormal plexiform vascular networks similar to the twig-like middle cerebral artery (MCA) that connected the proximal part of internal carotid artery stenosis to the proximal middle cerebral artery. Ethmoidal moyamoya vessels were also noted. A small plexiform vascular network was also observed around the stenosis of the left posterior cerebral artery, Although the plexiform vascular networks was similar to twig-like MCA that is regarded to be congenital, the location of these structures is different from where twig-like MCA exists, and recent onset of ischemic symptoms and hemodynamic disturbance suggested acquired disease. Therefore, we diagnosed her as NF1-related moyamoya syndrome (Suzuki staging of the right/left was stage III/IV). Whole-exome sequencing identified a missense variant of NF1 gene (c.2509T>C, p.W837R, rs587781747) with intact RNF213 gene. This NF1 missense gene variant may induce neurofibromin dysfunction and disruption of the Ras-MAPK pathway, leads to smooth muscle cell proliferation and thickening of the tunica intima, and causes arterial stenosis and these unique plexiform networks that is rarely observed in sporadic moyamoya disease.