Background: Brain/spine arteriovenous malformations (AVMs), cerebral aneurysms, and other cerebrovascular malformations linked to hemorrhagic stroke may be more frequently associated with an underlying genetic condition in pediatric and young adult patients than in older adults. However, the yield of clinical genetic testing for informing treatment and care in younger patients with hemorrhagic stroke has not yet been well characterized. Methods: We conducted a single-cohort retrospective analysis using electronic medical records from 2002–2025 of pediatric and young adult patients (aged 29 days to 25 years) who both had a diagnosis of non-traumatic hemorrhagic stroke and underwent genetic testing. Yield was quantified as the proportion of patients whose genetic testing results indicated the presence of either a definitive pathogenic variant (P), a likely pathogenic variant (LP), or a variant of uncertain significance (VUS). Results: Of 180 patients with non-traumatic hemorrhagic stroke, 57 (31.7%) underwent germline genetic testing, which included chromosomal microarray (CMA, n=12), gene panel (n=44), and whole exome or genome sequencing (WES or WGS, n=15). Median age at hemorrhagic stroke was 9.6 years; n=35 (61.4%) were male. Overall yield of genetic testing for P/LP variants was 20/57 (35.1%). Of the 31/57 patients (54.4%) with a brain/spine AVM, a P/LP variant was identified in 7/31. Of the 4/57 patients (7.0%) with a cerebral aneurysm, a P/LP variant was identified in 2/4. Of the 5/57 (8.8%) patients diagnosed with other cerebrovascular conditions (e.g., cavernous malformations, dural AV fistula), a P/LP variant was identified in 2/5. In the remaining 17/57 patients (29.8%) with an uncertain initial etiology of hemorrhagic stroke, a P/LP variant was identified in 8/17. Genetic testing led to diverse outcomes, including additional individual testing (n=8), family member testing (n=11), changes in medication regimen (n=6), changes in screening frequency (n=4), specialist referral (n=9), and other changes (n=5). Conclusion: In this cohort of pediatric and young adult hemorrhagic stroke patients, the yield of genetic testing was relatively high and changed management in a majority of cases. The subtype of hemorrhagic stroke likely influences the yield of testing. As testing was performed per clinician discretion, this yield may not be representative of larger cohorts where testing becomes universally offered, and further prospective studies are needed.
Chen et al. (Thu,) studied this question.