2026 American Academy of Neurology Autoimmune Abstract Website

Objective:

To describe diagnostic yield of whole exome (WES)/whole genome sequencing (WGS) testing in adult white matter diseases mimicking multiple sclerosis/neuroimmunological disorders.

To describe clinical, radiological features and treatment decisions made in select cases of white matter disease with pathogenic variants identified through such genetic testing.

Background:

An increasing number of monogenic mimics of neuro-inflammatory diseases are being identified through availability of genetic testing. Research remains limited in its utility in neuroimmunology clinic adults. We describe our single center experience of utility of such testing in terms of diagnostic yield and select examples of complex diagnoses and the impact of broad genetic testing on patient management.

Design/Methods:

This is a retrospective cases series of patients tested between 07/2025- 05/2026 with WES or WGS. We describe clinical and imaging characteristics of pathogenic or likely pathogenic variants and cumulative data on our experience in the clinic.

Results:

WGS/WES was completed in 14; results for 6 remain pending. Among completed cases, 4 (28%) yielded pathogenic or likely pathogenic variants and 6 (42%) had variants of uncertain significance (VUSes) with strong phenotypic correlation. 1 patient had three pathogenic variants explaining her complex symptomatology. Genetic etiologies included CSF1R disease, PSEN1-related dementia, channelopathies (CACNA1A1), NOTCH3 and 15q26 duplication disorder. Genomic testing findings led to reclassification of possible CNS demyelination/Multiple sclerosis in 3 patients and treatment modification in 1 patient. Other patients with VUSes (6/15) are planned to get functional testing/RNA sequencing for variant reclassification.

Conclusions:

There is an increasing need to use WGS/WES when diagnostic red flags are present in cases of suspected neuro-immune disorders.