title: Hereditary hemorrhagic telangiectasia: how accurate are the clinical criteria?
abstract: The clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria. Three out of four criteria are required for a definite clinical diagnosis HHT, two criteria are considered "possible" HHT, and 0 or 1 criterion makes the diagnosis unlikely. However, these consensus diagnostic criteria have not been validated. We report on the diagnostic accuracy of the clinical criteria. A total of 450 consecutive persons ≥16 years of age were screened for HHT between May 2004 and September 2009, including a chest CT to screen for pulmonary arteriovenous malformations (AVMs). We selected 263 first-degree relatives of disease-causing mutation carriers who underwent mutation analysis. Genetic test results were considered the gold standard. The family mutation was present in 186 patients (mean age 42.9 ± 14.6 yr; 54.8% female). A clinical diagnosis was definite, "possible", and unlikely in 168 (90.3%), 17 (9.1%), and 1 (0.5%) patient, respectively. In 77 persons the family mutation was absent (mean age 37.1 ± 12.3 yr, 59.7% female). In this group a clinical diagnosis was definite, possible, and unlikely in 0, 35 (45.5%), and 42 (54.5%) persons, respectively. The positive predictive value of a definite clinical diagnosis was 100% (95% CI 97.8-100), the negative predictive value of an unlikely diagnosis 97.7% (95% CI 87.9-99.6). Of 52 patients with "possible" HHT, 17 (32.7%) displayed an HHT-causing mutation. The Curaçao clinical criteria have a good diagnostic performance. Genetic testing is particularly helpful in patients with a "possible" clinical diagnosis HHT.
authors: Department of Cardiology, St. Antonius Hospital, Koekoekslaan, Nieuwegein, The Netherlands.
authors: Marco W F
authors: MW
authors: van Gent
authors: Sebastiaan
authors: S
authors: Velthuis
authors: Martijn C
authors: MC
authors: Post
authors: Repke J
authors: RJ
authors: Snijder
authors: Cornelis J J
authors: CJ
authors: Westermann
authors: Tom G W
authors: TG
authors: Letteboer
authors: Johannes J
authors: JJ
authors: Mager
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D004252:DNA Mutational Analysis; D000071063:Endoglin; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011859:Radiography; D011956:Receptors, Cell Surface / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000145:classification / Q000000981:diagnostic imaging* / Q000235:genetics; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface