Capillary Malformation-Arteriovenous Malformation Syndrome

Capillary Malformation-Arteriovenous Malformation (CM-AVM) is a syndrome first described in 2003 consisting of atypical capillary malformations (CMs) surrounded by a pale halo, associated in up to one-third of cases with fast-flow lesions: arteriovenous malformations (AVMs) or arteriovenous fistulas (AFVs). It is an autosomal dominant disease with high penetrance and high clinical variability. It can vary from only one CM to a diffuse limb involvement, called Parkes–Weber syndrome (PKWS) or intracranial fast-flow lesions. CM-AVM can be divided into two subtypes according to the causal genetic mutation: CM-AVM1 or CM-AVM2 if the mutation is found in RASA1 or EPHB4, respectively. RASA1 encodes for a RAS-GTPase-activating protein upstream of the RAS-RAF-MEK-ERK pathway that stimulates the hydrolyzation properties of RAS and thus decreases the underlying pathway. EPHB4 encodes for a transmembrane protein mostly found on endothelial cells. All known mutations are inactivating the corresponding protein causing a subsequent hyperactivation of the RAS-RAF-MEK-ERK pathway. Some clinical differences can be found between those two entities, but they mostly overlap. CM-AVM2 can also present a similar clinical presentation as hereditary hemorrhagic telangiectasia (HHT) and differentiating the two entities is not always straightforward. Treatment in an experienced and multidisciplinary center is tailored to each patient.