Criteria for the diagnosis of HAE nC1-INH include: (1) a history of recurrent angioedema in the absence of concomitant hives or use of medication known to cause angioedema; (2) documented normal or near normal C4, C1-INH antigen, and C1-INH function; and (3) either a genetic variant associated with the disease, or a family history of angioedema and documented lack of efficacy of chronic high-dose antihistamine therapy [16]. Here, COL18A1 is linked to hereditary angioedema.