How to Cite this Article: van Gent MWF, Velthuis S, Post MC, Snijder RJ, Westermann CJJ, Letteboer TGW, Mager JJ. 2013. Hereditary hemorrhagic telangiectasia: How accurate are the clinical criteria? Am J Med Genet Part A 161A: 461–466.
Hereditary hemorrhagic telangiectasia: How accurate are the clinical criteria?†
Article first published online: 8 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 3, pages 461–466, March 2013
How to Cite
van Gent, M. W.F., Velthuis, S., Post, M. C., Snijder, R. J., Westermann, C. J.J., Letteboer, T. G.W. and Mager, J. J. (2013), Hereditary hemorrhagic telangiectasia: How accurate are the clinical criteria?. Am. J. Med. Genet., 161: 461–466. doi: 10.1002/ajmg.a.35715
- Issue published online: 21 FEB 2013
- Article first published online: 8 FEB 2013
- Manuscript Accepted: 24 SEP 2012
- Manuscript Received: 22 NOV 2011
- HHT (Hereditary Hemorrhagic Telangiectasia);
- ENG (Endoglin);
- ACVRL1 (Activin receptor-like kinase);
- Clinical Criteria
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. © 2013 Wiley Periodicals, Inc.