Moyamoya syndrome in a patient with pathogenic heterozygous variant in the SETD5 gene: A case report

Abstract A 25-year-old patient with dysmorphic facies presented with tingling in both hands and a speech disorder that occurred for a few hours approximately once a month since the age of 12 years. A magnetic resonance angiography of the brain showed signs of a bilateral moyamoya phenomenon with distal carotid artery occlusions with significant collateral vessel formation and bilateral posterior cerebral artery occlusions. In addition, there was an extracranial, nonatherosclerotic carotid artery stenosis. Genetic testing identified a heterozygous de novo , loss-of-function variant in SETD5 , which was classified pathogenic according to the American College of Medical Genetics and Genomics criteria. This case report describes a newfound SETD5 pathogenic variant in a patient with moyamoya syndrome, but surprisingly without intellectual disability. Furthermore, our patient suffered from nonarteriosclerotic extracranial carotid artery stenosis, which is distinctly unusual in patients with moyamoya angiopathy. This raises the possibility that the occlusive vascular disease in patients with SETD5 variants may extend beyond the cerebrovascular circulation. In summary, this case presents a moyamoya patient with an unusual vascular feature which can be explained with the newfound SETD5 mutation variant.