The VHL tumor suppressor gene may be causally related to aneurysm formation through the effects of transcription factors, growth factors, and matrix metalloproteinases. Although a single point mutation is unlikely to be responsible for the complex phenotype of intracranial aneurysm, further research on aneurysmal domes and VHL gene expression may help validate the theory that extracellular matrix destruction is the final common pathway to aneurysm formation.