Division of Vascular Surgery, Department of Surgery, University of Washington, Seattle, Wash.
Departments of Pathology and Medicine (Medical Genetics), University of Washington, Seattle, Wash.
J Vasc Surg. 2020 Jan;71(1):149-157. doi: 10.1016/j.jvs.2019.04.487. Epub 2019 Jul 26.
Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015.
This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation.
Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.
This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.
血管型埃勒斯-当洛斯综合征（vEDS）是一种罕见疾病，是 13 种埃勒斯-当洛斯综合征中的 1 种。该综合征会导致主动脉和动脉在年轻时出现动脉瘤和夹层。通过皮肤活检或 COL3A1 致病性变异的基因检测，可确认诊断。我们描述了 2000 年至 2015 年间对血管型 EDS 的多机构诊断经验。
这是一项针对血管型 EDS 患者的多机构横断面回顾性研究。该研究通过血管低频疾病联合会招募了多家机构。通过国际疾病分类第 9 版和第 10 版-CM 代码（756.83 和 Q79.6）识别个体。然后对记录进行回顾性分析，以选择血管型 EDS 患者。数据提取包括人口统计学、家族史、临床特征、主要和次要诊断标准以及分子检测结果。将个体分为两个队列，然后进行比较：具有致病性 COL3A1 变异的个体和仅通过临床标准诊断而未经分子证实的个体。
11 家机构共确定了 173 名血管型 EDS 患者（35.3%为男性，56.6%为白种人）。其中 11 名（9.8%）COL3A1 存在非致病性改变，因此被排除在分析之外。在其余个体中，86 名（47.7%为男性，68%为白种人，48.8%有阳性家族史）存在致病性 COL3A1 变异，76 名（19.7%为男性，19.7%为白种人，43.4%有阳性家族史）仅通过临床标准诊断而未经分子证实。与具有致病性 COL3A1 变异的队列相比，仅通过临床标准诊断的队列中女性比例更高（80.3%比 52.3%；P<0.001），二尖瓣脱垂（10.5%比 1.2%；P=0.009）和关节过度活动（68.4%比 40.7%；P<0.001）更为常见。此外，该队列中易瘀伤的频率较低（23.7%比 64%；P<0.001），皮肤薄而透明（17.1%比 48.8%；P<0.001），肠穿孔（3.9%比 16.3%；P=0.01），自发性气胸/血胸（3.9%比 14%，P.03）和动脉破裂（9.2%比 17.4%；P=0.13）的发生率较低。两个队列的死亡率或死亡年龄无差异。
本研究强调了通过检测致病性 COL3A1 变异而不是仅依赖临床诊断标准来确认血管型 EDS 诊断的重要性，因为这与其他遗传性动脉病变高度重叠。由于并非所有 COL3A1 变异均具有致病性，因此由受过变异评估培训的人员对基因检测结果进行解释对于确认诊断至关重要。准确的诊断至关重要，对受影响个体和家庭成员的终生筛查和治疗策略具有严重影响。
