Department of Cardiology, St. Antonius Hospital, Koekoekslaan, Nieuwegein, The Netherlands.
Am J Med Genet A. 2013 Mar;161A(3):461-6. doi: 10.1002/ajmg.a.35715. Epub 2013 Feb 8.
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.
遗传性出血性毛细血管扩张症（HHT）的临床诊断基于 Curaçao 标准。四项标准中符合三项即可明确诊断 HHT，符合两项则考虑“可能”HHT，而仅符合一项则不太可能诊断为 HHT。然而，这些共识性诊断标准尚未经过验证。我们报告了这些临床标准的诊断准确性。2004 年 5 月至 2009 年 9 月期间，我们对 450 名年龄≥16 岁的连续患者进行了 HHT 筛查，包括胸部 CT 以筛查肺动静脉畸形（AVM）。我们选择了 263 名致病突变携带者的一级亲属进行突变分析。基因检测结果被视为金标准。在 186 名患者（平均年龄 42.9 ± 14.6 岁；54.8%为女性）中发现了家族突变。临床诊断分别为明确、“可能”和不太可能的患者各有 168 例（90.3%）、17 例（9.1%）和 1 例（0.5%）。在 77 名未携带家族突变的患者中（平均年龄 37.1 ± 12.3 岁，59.7%为女性），分别有 0、35 例（45.5%）和 42 例（54.5%）患者的临床诊断为明确、“可能”和不太可能。明确临床诊断的阳性预测值为 100%（95%CI 97.8-100），不太可能诊断的阴性预测值为 97.7%（95%CI 87.9-99.6）。在 52 例“可能”HHT 患者中，有 17 例（32.7%）存在 HHT 致病突变。Curaçao 临床标准具有良好的诊断性能。基因检测对于“可能”HHT 的临床诊断患者尤其有帮助。
