Rapid Whole Genome Sequencing Boosts Neurologic Diagnosis
RAPID whole genome sequencing delivered likely genetic diagnoses in nearly one quarter of hospitalized adults with unexplained neurologic symptoms.
Findings presented at AAN 2026 in Chicago, Illinois, suggest that rapid whole genome sequencing may help resolve some of the most complex inpatient neurology cases, particularly when standard evaluation leaves clinicians without a clear explanation. In this retrospective review, investigators examined hospitalized adults with prolonged stays who underwent rapid whole genome sequencing after the treating team suspected a genetic contributor to multifocal neurologic disease.
Rapid Whole Genome Sequencing in Complex Inpatient Neurology
The analysis included 58 adults drawn from a larger group of 96 hospitalized individuals who had undergone rapid whole genome sequencing between June 2022 and September 2025. All patients in this neurologic subgroup had complex presentations, and the mean age was 53 years. Ataxia was the most common feature, reported in 27% of patients, followed by epilepsy in 20%.
After detailed phenotype evaluation, 14 of the 58 patients, or 24%, were found to have variants that matched their clinical presentation. Ten patients carried pathogenic or likely pathogenic variants. A further four had variants of uncertain significance that, after reverse phenotyping, were considered explanatory for the neurologic manifestations. All 14 of these patients were ultimately found to have monogenic disorders.
What the Diagnostic Yield Means for Practice
The findings point to meaningful clinical value for rapid whole genome sequencing in adult inpatient neurology, an area where evidence has remained limited compared with pediatric practice. In this cohort, the technology did not simply generate genetic data. It produced definitive or likely answers in a substantial minority of difficult cases that had already required prolonged hospitalization.
That level of diagnostic yield could have important downstream implications for care. A faster genetic explanation may help direct management, reduce diagnostic uncertainty, and support more informed counseling for patients and families. It may also help clinicians avoid extended diagnostic pathways in adults with unexplained neurologic manifestations, especially when the phenotype is broad, multifocal, or atypical.
While the study was retrospective and reflects a selected inpatient population in whom a genetic cause was already suspected, the results reinforce the growing role of rapid whole genome sequencing as a practical diagnostic tool in adult neurology.
Reference
Amanat M et al. Diagnostic Yield of Rapid Whole Genome Sequencing in Hospitalized Adults with Unexplained Neurological Manifestations. Abstract 7-001. AAN Annual Meeting, 18-22 April, 2026.
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