Ruptured intracranial aneurysm associated with von Hippel-Lindau syndrome: a molecular link?
Paraules clau
Resum
OBJECTIVE
Research into the etiopathogenesis of intracranial aneurysms has failed to demonstrate molecular markers or pathognomonic genetic sequences. The authors describe the case of aneurysmal rupture in a patient with von Hippel-Lindau (VHL) syndrome and explore a possible molecular link.
METHODS
A 17-year-old girl underwent endovascular coiling for an aneurysmal subarachnoid hemorrhage. Six years later, she developed spinocerebellar hemangioblastomas. Gene sequencing revealed a heterozygous, germline point mutation at nucleotide 469 in the VHL locus on chromosome 3. The mutation changed a codon for proline (CCC) to one for serine (TCC) at amino acid position 86.
CONCLUSIONS
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.
