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Abstract
Recent advances in cerebrovascular genomics, single-cell biology, pharmacology, and gene editing technology are transforming our understanding of brain arteriovenous malformations (bAVMs) — a leading cause of pediatric hemorrhagic stroke. Once considered static anatomical defects, bAVMs are now recognized as dynamic, genetically driven lesions resulting from somatic mutations in KRAS, BRAF, and pathways involved in arteriovenous specification, angiogenesis, and vascular remodeling. By integrating human genetics, animal models, and endovascular innovations, researchers have uncovered convergent mechanisms that link endothelial Ras/MAPK hyperactivation to abnormal vessel growth and higher rupture risk. These insights provide a foundation for precision medicine approaches that combine molecular diagnostics — such as liquid or endoluminal biopsies — with mutation-specific pharmacotherapies and emerging CRISPR-based gene editing strategies. We suggest that genotype-guided interventions, tailored by spatial and developmental cerebrovascular context, could ultimately reclassify bAVMs from surgically incurable malformations to treatable molecular conditions.
Authors
Andrew T. Hale, Adam J. Kundishora, Pazhanichamy Kalailingam, Tanyeri Barak, Phan Q. Duy, Christopher M. Ramundo, Baojian Fan, Qiang Li, Priscilla K. Brastianos, Ganesh M. Shankar, Seth L. Alper, Benjamin P. Kleinstiver, Patricia L. Musolino, Kristopher T. Kahle
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ISSN: 0021-9738 (print), 1558-8238 (online)