Developmental venous anomalies are a genetic primer for cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are a neurovascular anomaly that may occur sporadically, or be inherited due to autosomal dominant mutations in , , or . Individual lesions are caused by somatic mutations which have been identified in and . However, the interactions between mutations, and their relative contributions to sporadic versus familial cases remain unclear. We show that mutations in are mutually exclusive, but may co-occur with mutations in We also find that mutations may cause sporadic, but not familial CCM. Furthermore, we find identical mutations in CCMs and adjacent developmental venous anomalies (DVA), a common vascular malformation frequently found in the vicinity of sporadic CCMs. However, somatic mutations in are found only in the CCM. This suggests that sporadic CCMs are derived from cells of the DVA which have acquired an additional mutation in .