Capillary malformation-arteriovenous malformation and RASA1 mutations

Capillary malformation–arteriovenous malformation (CM–AVM) is a subtype of CM that is inherited as an autosomal-dominant disorder. Patients typically have multiple small pinkish-reddish CMs, often with a halo. These lesions are randomly distributed on the body. About 15–20% of patients have an associated arteriovenous fistula or malformation often located on head and neck. The fast-flow lesions involve skin, subcutaneous tissue, muscle and/or bone or the brain or the spine. Parkes Weber syndrome and vein of Galen aneurysmal malformation are also part of CM–AVM. Most CM–AVM patients have a detectable RASA1 mutation causing loss-of-function of p120RASGAP, a guanosine triphosphatase-activating protein, which participates in the regulation of the Ras signalling pathway. Most mutations are private and no genotype–phenotype correlation has been identified. A somatic second hit is likely necessary to produce lesional, complete loss-of-function of p120RASGAP, as the malformations are localised, and often multifocal. Ras-pathway modulators may provide futuristic therapies for CM–AVM