Conversely, there are a few reports of patients carrying biallelic non-missense NOTCH3 variants, particularly frameshift or premature stop-gain variants, exhibiting a neurodevelopmental phenotype with early leukoencephalopathy and stroke.14, 15, 16, 17 Nevertheless, these reports are scarce and necessitate a more extensive case study to conclusively establish their causative nature and elucidate detailed phenotypic characteristics. This evidence concerns the gene NOTCH3 and Stroke.