Abstract Body: Introduction: Pediatric and young adult cerebrovascular disease is more commonly associated with genetic conditions compared to in adults. This pilot study aims to characterize utility of genetic testing in a pediatric and young adult neurovascular clinic.

Methods: This was a single center cohort study of pediatric and young adult patients (age <25 years) with cerebrovascular conditions who underwent clinical genetic testing between 7/2023-7/2024. Cerebrovascular conditions included brain or spine AVM, cavernous malformation, cerebral aneurysm, Moya-Moya vasculopathy, and/or unexplained hemorrhagic stroke. Individuals with perinatal or isolated arterial ischemic stroke were not included. Genetic testing ranged from a custom gene panel (including 4-175 genes) to whole exome/genome sequencing. Chart review was performed by a pediatric vascular neurologist to determine clinical details and genetic results. Identified genetic variants were further classified as 1) pathogenic or highly suspicious, 2) actionable but unrelated to phenotype, and 3) possibly relevant.

Results: Twenty patients underwent genetic testing, including 7 with brain or spine AVM, 3 with ruptured cerebral aneurysm, 5 with spontaneous intracranial hemorrhage without underlying vascular malformation, and 5 with other cerebrovascular malformations. Median age at testing was 14 years (range 2mo – 24 years), and 11 (55%) were male. Panel testing was performed on 16/20; exome/genome trio sequencing was performed in 4/20. Definite pathogenic or highly suspicious variants relevant to underlying phenotype were noted in 4/20 (20%), an unrelated but actionable pathogenic variant was noted in 1/20 (5%), and possibly relevant variants were noted in an additional 3/20 (15%) patients. Genes with identified variants included RNF213 (n=2), ENG, EPHB4, F2, F5, COL4A1, and DIAPH1. Positive or negative results informed or changed clinical management in 17/20 (85%) patients, prompting additional testing, altered imaging surveillance, and/or expectant guidance for the patient and family members.

Conclusions: Genetic testing has become increasingly available and has relatively high yield in pediatric and young adult hemorrhagic stroke and cerebrovascular malformations. Panel or exome/genome-based testing can inform care in these individuals and their families. Larger cohort studies are needed to determine more precise yield of genetic testing across a variety of cerebrovascular conditions.