血管型埃勒斯-当洛斯综合征患者在三级转诊中心的临床诊断标准的准确性。

Accuracy of Clinical Diagnostic Criteria for Patients With Vascular Ehlers-Danlos Syndrome in a Tertiary Referral Centre.

机构信息

AP-HP, Hôpital Européen Georges Pompidou, Département de Génétique, Centre de Référence des Maladies Vasculaires Rares, Paris (P.H., J.A., S.A., A.L.,J.M.M., X.J., M.F.).

Médecine Interne et Maladies Vasculaires, Hôpital Saint-éloi, Centre Hospitalier Régional Universitaire de Montpellier (P.H.).

出版信息

Circ Genom Precis Med. 2019 Mar;12(3):e001996. doi: 10.1161/CIRCGEN.117.001996.

DOI:10.1161/CIRCGEN.117.001996

PMID:30919682

Abstract

BACKGROUND

Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disease secondary to mutations within the COL3A1 gene. The diagnosis of vascular Ehlers-Danlos syndrome is challenging, and patient selection for genetic testing relies on diagnostic criteria, which have never been evaluated.

METHODS

All patients seen at a dedicated tertiary referral center for a suspicion of vascular Ehlers-Danlos syndrome between January 2001 and March 2016 were retrospectively included in a diagnostic accuracy study. Major and minor diagnostic criteria of the Villefranche classification were tested for sensitivity, specificity, positive and negative predictive values, according to results of genetic testing.

RESULTS

N=519 patients were eligible for analysis dividing into n=384 probands and n=135 relatives. A pathogenic COL3A1 variant was identified in n=165 (31.8%) patients. The Villefranche criteria were met for n=248 patients with a sensitivity of 79% (95% CI, 0.72-0.85) and a negative predictive value of 87% (95% CI, 0.83-0.91). Diagnostic accuracy was highest for symptomatic probands (sensitivity 92%; negative predictive value 95%) with limited specificity (60%). Probands ≤25 years had the worst diagnostic performance. The revised diagnostic Criteria (2017) were less accurate than the Villefranche classification (overall diagnostic odds-ratio, 4.17 versus 7.8; probands diagnostic odds-ratio, 4.04 versus 18.1; and probands ≤25 years diagnostic odds-ratio, 2.36 versus 5.1) mainly due to a lack of sensitivity.

CONCLUSIONS

The Villefranche criteria provide accurate detection of symptomatic probands in specialized practice but have limited specificity. The revised diagnostic criteria for vascular Ehlers-Danlos syndrome have increased specificity, but its overall performance is poorer. The early clinical diagnosis of probands without family history is not addressed by both diagnostic classifications.

摘要

背景

血管型 Ehlers-Danlos 综合征是一种罕见的遗传性结缔组织疾病，继发于 COL3A1 基因突变。血管型 Ehlers-Danlos 综合征的诊断具有挑战性，基因检测的患者选择依赖于诊断标准，但这些标准从未经过评估。

方法

2001 年 1 月至 2016 年 3 月期间，我们对一家专门的三级转诊中心怀疑为血管型 Ehlers-Danlos 综合征的所有患者进行了回顾性研究，这些患者都被纳入诊断准确性研究。根据基因检测结果，对血管型 Ehlers-Danlos 综合征分类的主要和次要诊断标准进行了敏感性、特异性、阳性和阴性预测值的检测。

结果

我们共纳入了 519 名符合条件的患者，分为 384 名先证者和 135 名亲属。在 165 名（31.8%）患者中发现了致病性 COL3A1 变异。248 名患者符合血管型 Ehlers-Danlos 综合征分类标准，其敏感性为 79%（95%可信区间，0.72-0.85），阴性预测值为 87%（95%可信区间，0.83-0.91）。有症状的先证者的诊断准确性最高（敏感性 92%，阴性预测值 95%），但特异性有限（60%）。≤25 岁的先证者的诊断效能最差。与血管型 Ehlers-Danlos 综合征分类标准（总体诊断优势比，4.17 对 7.8；先证者诊断优势比，4.04 对 18.1；≤25 岁先证者诊断优势比，2.36 对 5.1）相比，修订后的诊断标准准确性较低，主要是因为敏感性较低。