Controversial Molecular Classification of Human Cerebrovascular Malformations

To the Editor: The identification of underlying causal genes in familial forms of cerebrovascular malformations allows the dissection of an increasing number of these disorders at the molecular level. In recent years, mutations in CCM1/KRIT1 , CCM2/MGC4607 , and CCM3/PDCD10 have been found to cause autosomal dominantly inherited cerebral cavernous malformations (CCM1, CCM2, and CCM3). Clinical penetrance appears to differ between the 3 CCM subtypes, but larger clinical studies are required to confirm this observation. A subset of patients with cerebral arteriovenous malformations also shows cutaneous capillary malformations attributable to mutations in the RASA1 gene or is affected by hereditary hemorrhagic telangiectasias (HHT) resulting from mutations in the endoglin gene ( ENG , HHT1), the activin receptor-like kinase1 gene …