Angioedema, hereditary, 4

Hereditary angioedema-4 (HAE4) is an autosomal dominant disorder characterized by episodic subcutaneous or submucosal edema with onset usually in adulthood. Swelling most commonly involves the face and tongue, sometimes resulting in occlusion of the airway, which can cause death. The larynx, abdomen, and limbs may also be involved. Circulating C1 inhibitor (C1INH) levels and function, as well as plasminogen levels and activity, are normal. Although the disorder is autosomal dominant, there is evidence of incomplete penetrance, variable expressivity, and female predominance. The episodes may be triggered by stress, oral contraceptives, ACE inhibitors, and angiotensin II receptor blockades. The pathogenesis is believed to be due to altered plasmin function resulting in enhanced release of bradykinin. Successful clinical management has been achieved with tranexamic acid, which inhibits plasmin, and icatibant, a selective bradykinin B2 receptor (113503) antagonist (summary by Farkas et al., 2021). For a discussion of genetic heterogeneity of HAE, see 106100. [from OMIM]