NOTCH3 and CADASIL: Despite the heterogeneous nature of the phenotype, a definitive diagnosis of CADASIL is completed through either the identification of characteristic cysteine altering mutations between exons 2 and 24 in NOTCH3, or through the presence of granular osmiophilic material (GOM) identified by a tissue biopsy (Mancuso et al., 2020; Mizuta et al., 2017; Ueda et al., 2009).