Patients with NOTCH3 LoF variants exhibit leukovasculopathy with periventricular leukomalacia-like patterns in neuroimaging, which are likely related to brain small vessel injury and ischemic insult in early stages of life or even prenatal as shown in preterm hypoxic-ischemic encephalopathy,40 which must be considered as a differential diagnosis. This evidence concerns the gene NOTCH3 and perinatal asphyxia.