Hereditary angioedema is a genetic disorder characterized by recurrent episodes of subcutaneous or submucosal edemas affecting various parts of the body including hands, feet, intestinal tract, and larynx. The condition can be life-threatening in certain cases where it causes occlusion in the upper airway resulting in asphyxiation. Factors that trigger episodes vary and symptoms typically last 48 to 72 hours, but they can last upto one week.
The disease results from deficiency of the plasma protein C1 inhibitor. Two distinct categories of hereditary angioedema are now recognized. Type I affects approximately 85% of all patients with hereditary angioedema and is characterized by low antigenic and functional levels of C1 inhibitor. Type II is found in approximately 15% of patients with hereditary angioedema and is defined by normal or elevated levels of C1 inhibitor with low functional activity caused by the secretion of a dysfunctional protein. The prevalence of the disease has been estimated at 1/50 000, with no reported bias in different ethnic groups.
Hereditary angioedema is caused by mutation in the C1 inhibitor gene comprising eight exons. Rare mutations causing deficiency or dysfunction of C1 inhibitor have been identified throughout the entire length of the gene, as well as common sequence variations of unknown significance. Moreover, the C1 inhibitor locus has clusters of intragenic Alu repeats that predispose to deleterious gene rearrangements. Such gross alterations in the C1 inhibitor gene have been reported in up to 20% of individuals with type I hereditary angioedema. The spontaneous mutation rate is about 25% and more than 100 different C1 inhibitor gene mutations have been described.