SERPING1 and Down syndrome: While types 1 and 2 HAE are well-established entities caused by quantitative and qualitative defects in C1-INH, respectively, the emergence of type 3 HAE, also known as estrogen-dependent HAE, has expanded our understanding of this complex disorder. In this case, a 2-year-old girl with Down syndrome visited the ER after experiencing lip and tongue swelling following the ingestion of ground pepper.