The diagnostic criteria for MS continue to be refined [33], and while genetic testing for other diseases is not required, several of the diseases implicated by diagnostic ‘red flags’ are genetic, including spastic paraplegias (KIF5A) and CADASIL (NOTCH3 – see also Mandler et al. [15]) as identified in this study, and can potentially be ruled in or out using clinical genome sequencing. Here, NOTCH3 is linked to Spastic paraplegia.