Misdiagnosis of MS can result in negative neurologic outcomes. iLEs can present similarly to MS, but are not often considered in the differential diagnosis.

‘Atypical MS’ patients had a prior MS diagnosis and were referred for neurogenetics evaluation between 2015-2022. We retrospectively reviewed charts to determine whether patients met 2017 McDonald Criteria for relapsing-remitting (RRMS) or primary-progressive (PPMS) MS, exhibited ‘red flag’ features (Solomon et al, Lancet Neurol, 2023), and whether they had genetic testing results.

Of the ‘atypical MS’ patients (N=61), 29 (47.5%) were diagnosed with RRMS and 32 (52.5%) with PPMS. Only 37.7% met 2017 McDonald criteria; 3 patients had insufficient data available. Thirty-nine patients (63.9%) received MS disease-modifying therapy. Most atypical MS patients had historical red flags (N=48). The most common red flags were positive family history (N=21), onset after age 50 (N=8), presence of extrapyramidal features (N=8), and isolated progressive myelopathy (N=7). There was no difference in the frequency of red flags between patients who met diagnostic criteria and those who did not. Genetic disorders were identified in 5 patients: CADASIL (N=2), KIF1A Disorder, Spastic Paraplegia Type 7, and MERRF-like syndrome, all of whom exhibited red flags. Broad-based next-generation sequencing was performed in less than half of cases (N=23).

Most patients undergoing neurogenetics evaluation exhibited MS red flags and did not meet diagnostic criteria. Genetic testing was diagnostic in a subset (5/61, 8%). Most patients had insufficient access to broad-based clinical next-generation sequencing, such as whole exome or whole genome sequencing. Our goal is to obtain affordable, broad-based genetic testing in all patients to better evaluate for genetic disorders.