Furthermore, genetic testing may confirm the diagnosis in those with limited symptoms who otherwise would have been labeled "possible HHT" (see below).Genetic diagnosis in HHT is difficult, as mutations occur in numerous different locations in the linked genes, without particular mutations being highly frequent (as opposed to, for instance, the ΔF508 mutation in cystic fibrosis). Sequence analysis of the involved genes is therefore the most useful approach (sensitivity 75%), followed by additional testing to detect large deletions and duplications (additional 10%). Not all mutations in these genes have been linked with disease.Mutations in the MADH4 gene is usually associated with juvenile polyposis, and detection of such a mutation would indicate a need to screen the patient and affected relatives for polyps and tumors of the large intestine. Criteria
The diagnosis can be made depending on the presence of four criteria, known as the "Curaçao criteria". If three or four are met, a patient has "definite HHT", while two gives "possible HHT":

Spontaneous recurrent epistaxis
Multiple telangiectasias in typical locations (see above)
Proven visceral AVM (lung, liver, brain, spine)
First-degree family member with HHTDespite the designation "possible", someone with a visceral AVM and a family history but no nosebleeds or telangiectasias is still extremely likely to have HHT, because these AVMs are very uncommon in the general population. At the same time, the same cannot be said of nosebleeds and sparse telangiectasias, both of which occur in people without HHT, in the absence of AVMs.
AVMs are probably present from birth, but dont necessarily cause any symptoms. Frequent nosebleeds are the most common symptom and can significantly affect quality of life. History
Several 19th century English physicians, starting with Henry Gawen Sutton (1836–1891) and followed by Benjamin Guy Babington (1794–1866) and John Wickham Legg (1843–1921), described the most common features of HHT, particularly the recurrent nosebleeds and the hereditary nature of the disease. The French physician Henri Jules Louis Marie Rendu (1844–1902) observed the skin and mucosal lesions, and distinguished the condition from hemophilia. The Canadian-born Sir William Osler (1849–1919), then at Johns Hopkins Hospital and later at Oxford University, made further contributions with a 1901 report in which he described characteristic lesions in the digestive tract. The English physician Frederick Parkes Weber (1863–1962) reported further on the condition in 1907 with a series of cases. The term "hereditary hemorrhagic telangiectasia" was first used by the American physician Frederic M. Hanes (1883–1946) in a 1909 article on the condition.The diagnosis of HHT remained a clinical one until the genetic defects that cause HHT were identified by a research group at Duke University Medical Center, in 1994 and 1996 respectively. In 2000, the international scientific advisory committee of cureHHT formerly called the HHT Foundation International published the now widely used Curaçao criteria. In 2006, a group of international experts met in Canada and formulated an evidence-based guideline, sponsored by cureHHT. This guideline has since been updated in 2020 and can be found here. == References ==