About the disease

Scientific Evolution of HAE

Key milestones that transformed the diagnosis and understanding of Hereditary Angioedema.

Timeline

  1. 1882 Heinrich Quincke described acute swelling of the skin and mucous membranes.
  2. 1888 William Osler identified the hereditary pattern by observing cases within the same family.
  3. 1963 Donaldson and Evans identified the deficiency of C1-INH as the cause of HAE.
  4. 1986 R. P. Warin and colleagues made the first description of HAE with normal C1-esterase.
  5. 2000 Konrad Bork and colleagues presented one of the first series of patients with normal C1-INH and proposed HAE type III.
  6. 2006 Dewald, Bork and Cichon described the molecular basis of HAE with normal C1-INH involving mutations in the F12 gene.
  7. 2011 Konrad Bork and colleagues described a mutation in the F12 gene (72-base deletion).
  8. 2013 Nora Kiss and colleagues identified a new mutation in the F12 gene (18-base duplication).
  9. 2017 Valeria Bafunno and colleagues identified a mutation in the ANGPT1 gene associated with HAE with normal C1-INH; and Konrad Bork and colleagues described mutations in the PLG gene.
  10. 2019 Konrad Bork and colleagues found a mutation in the KNG1 gene (kininogen 1).
  11. 2020 Anastasia Ariano and colleagues identified a mutation in the MYOF gene (myoferlin) in patients with normal C1-INH.
  12. 2021 Konrad Bork and colleagues described a mutation in the HS3ST6 gene, associated with HAE with normal C1-INH.

Why is this important?

Over the past decades, scientific advancement has made it possible to understand that HAE is not a common allergy, but a condition primarily mediated by mechanisms involving bradykinin. This knowledge has enabled improved diagnosis and the development of specific treatments.