Genetic test indications and interpretations in patients with hereditary angioedema

Patients with hereditary angioedema (HAE) present with recurrent, circumscribed, and self-limiting episodes of tissue or mucous membrane swelling caused by C1-inhibitor (CI-INH) deficiency. The estimated frequency of HAE is 1:50,000 persons. Distinguishing HAE from acquired angioedema (AAE) facilitates therapeutic interventions and family planning or testing. Patients with HAE benefit from treatment with attenuated androgen, antifibrinolytic agents, and C1-INH concentrate replacement during acute attacks. HAE is currently recognized as a genetic disorder with autosomal dominant transmission. Other forms of inherited angioedema that are not associated with genetic mutations have also been identified. Readily available tests are complement studies, including C4 and C1-esterase inhibitor, both antigenic and functional C1-INH. These are the most commonly used tests in the diagnosis of HAE. Analysis of C1q can help differentiate between HAE and AAE caused by C1-INH deficiency. Genetic tests would be particularly helpful in patients with no family history of angioedema, which occurs in about half of affected patients, and in patients whose C1q level is borderline and does not differentiate between HAE and AAE. Measuring autoantibodies against C1-INH also would be helpful, but the test is available in research laboratories only. Simple complement determinations are appropriate for screening and diagnosis of the disorder.