We sought to determine the diagnostic yield and clinical impact of genetic testing in pediatric and young adult patients with hemorrhagic stroke.

Brain/spine arteriovenous malformations (AVMs), cerebral aneurysms, and other cerebrovascular malformations may have significant genetic underpinnings in younger patients with hemorrhagic stroke, but the yield of genetic testing in informing clinical outcomes remains unclear.

We conducted a single-center retrospective study of pediatric and young adult patients (ages 29 days–25 years) evaluated between 2002–2025 for non-traumatic hemorrhagic stroke who underwent germline genetic testing. Diagnostic yield was quantified as the proportion with a pathogenic/likely pathogenic genetic variant (P/LP) or a variant of uncertain significance (VUS).

Of 180 eligible patients, 57 (31.7%) underwent germline testing: chromosomal microarray (CMA, n=12), gene panel (n=44), and/or whole exome/genome sequencing (WES/WGS, n=15). Median age at stroke was 9.6 years; 61.4% were male. The overall yield of genetic testing for P/LP variants was 20/57 (35.1%). Among patients with a brain/spine AVM (n=31), 7/31 had a P/LP variant. Among patients with a cerebral aneurysm (n=4), 2/4 had a P/LP variant. Among patients with other cerebrovascular malformations (n=5), 2/5 had a P/LP variant, and in patients with an uncertain initial stroke etiology (n=17), 8/17 had a P/LP variant. Genetic testing prompted a range of management changes, including additional individual testing (n=8), family member testing (n=11), medication changes (n=6), altered screening frequency (n=4), specialist referral (n=9), and other modifications (n=5).

In this cohort of pediatric and young adult hemorrhagic stroke patients, the yield of genetic testing was relatively high and changed management in most cases. Notably, five of six recurrent P/LP genes identified (COL4A1, COL4A2, RNF213, ENG, PTEN) possess established cerebrovascular disease associations, reinforcing the biological specificity of genetic testing in this population. As testing was clinician-directed, prospective studies in larger cohorts with universal testing are warranted to improve generalizability.