Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Am J Med Genet A. 2010 Feb;152A(2):413-6. doi: 10.1002/ajmg.a.32856.
Aortic aneurysm and dissection cause significant morbidity and mortality. There are several known single gene disorders that predispose to isolated aortic disease and eventually aneurysm and dissection. FBN1 mutations are associated with multiple clinical phenotypes, including Marfan syndrome (MFS), MASS phenotype, and familial ectopia lentis, but rarely with isolated aortic aneurysm and dissection. In this report, we describe three patients who presented with primary descending thoracic aortic dissection and who were found to have an FBN1 mutation. None of the patients fulfilled clinical criteria for the diagnosis of MFS, and all had few or none of the skeletal features typical of the condition. Two patients had a history of long-term hypertension, and such a history was suspected in the third patient. These observations suggest that some individuals with FBN1 mutations have significant aortic disease involvement of other systems that is typical of FBN1 mutation-related syndromes. Superimposed risk factors, such as hypertension, may weaken the aortic wall and eventually lead to aortic dissection. Given that the cost continues to decrease, we suggest that diagnostic DNA sequencing for FBN1 mutations in patients with thoracic aortic aneurysms and dissection may be a practical clinical step in evaluating such patients and at-risk family members.
主动脉瘤和夹层会导致严重的发病率和死亡率。有几种已知的单基因疾病会导致孤立性主动脉疾病，最终导致动脉瘤和夹层。FBN1 突变与多种临床表型相关，包括马凡综合征（MFS）、MASS 表型和家族性晶状体异位，但很少与孤立性主动脉瘤和夹层相关。在本报告中，我们描述了 3 名出现原发性降主动脉夹层的患者，他们被发现存在 FBN1 突变。这些患者均不符合 MFS 的临床诊断标准，且均仅有少数或无典型马凡综合征的骨骼特征。2 名患者有长期高血压病史，第 3 名患者疑似有此病史。这些观察结果表明，一些 FBN1 突变的个体存在其他系统的显著主动脉疾病，这是与 FBN1 突变相关综合征的典型表现。高血压等叠加危险因素可能会削弱主动脉壁，最终导致主动脉夹层。鉴于成本持续降低，我们建议对患有胸主动脉瘤和夹层的患者进行 FBN1 突变的诊断性 DNA 测序，可能是评估此类患者和高危家族成员的一种实用临床步骤。
