Familial patterns of thoracic aortic aneurysms
Familial patterns of thoracic aortic aneurysms
复制标题
DOI：
10.1001/archsurg.134.4.361
复制
发表时间：
1999-04-01
影响因子：
--
通讯作者：
Elefteriades, JA
中科院分区：
文献类型：
--
作者：
Coady, MA;Davies, RR;Elefteriades, JA
假设：通过证明胸主动脉瘤（TAA）的家族性模式，提供遗传因素有助于TAA发展的证据。设计：回顾性分析。地点：大学医院。患者和方法：我们试图从耶鲁大学胸主动脉疾病中心（New Haven，Conn）的598例接受评估或治疗的TAA患者的数据库中确定TAA的家族模式，从1985年1月到1998年8月。在598名患者中，45名患者被诊断为马凡氏综合征，553名患者没有任何已知的胶原血管疾病病史。在后一类别的553例患者中，398例患者证实了TAA，66例患者患有TAA伴主动脉夹层，89例患者患有主动脉夹层。从464例伴或不伴主动脉夹层的TAA患者中，2名访谈者试图联系150例随机选择的患者进行电话筛查，以确定是否存在家族性主动脉疾病模式。其中15例患者失访。对其余135例患者（85例男性，50例女性）的完整病史和家族史进行了审查。在135名受检者中，26名（18名男性，8名女性）（19.3%）被发现属于多重家系。这26例家族性非综合征性TAA与其余109例散发性TAA和45例与马凡氏综合征相关TAA.Main结局指标：年龄和主动脉大小在诊断时，TAA的增长率和伴随疾病的发生率进行了统计学差异的研究。对非综合征家系进行分析，并确定潜在的遗传方式。家族性非综合征型TAA患者的平均就诊年龄（56.8岁）明显小于散发病例的平均发病年龄（64.3岁，P ≤ 0.03），明显大于马凡氏综合征患者（24.8岁，P ≤ 0.001）。与散发性TAA患者（0.03 cm/y）（P小于或等于0.001）和马凡氏综合征患者（0.10 cm/y）（P小于或等于0.04）相比，有主动脉瘤家族史的患者的生长速度更快（0.22 cm/y）。家族性非综合征性TAA合并主动脉夹层患者的生长率为0.33 cm/y，高于散发性TAA患者（0.10 cm/y）和马凡综合征合并主动脉夹层患者（0.08 cm/y）。0.33 cm/y的生长速度明显快于主动脉夹层患者动脉瘤的总体生长速度估计值（0.14 cm/y）（P小于或等于0.05）。10个家系（38.5%）显示直接父传子，符合常染色体显性遗传方式。6个家系（23.1%）为常染色体显性遗传或X连锁遗传。7个家系（26.9%）为隐性遗传，2个为常染色体隐性遗传，5个为X连锁或常染色体隐性遗传。其余3个家系表现出更复杂的遗传方式。结论：本研究支持遗传因素影响TAA家族聚集性的作用。与多发性家系相关的胸主动脉瘤是动脉瘤生长的一个新的危险因素。系谱分析提示遗传异质性。主要的遗传方式似乎是常染色体显性，但X连锁显性和隐性模式也很明显。
Hypothesis: To provide evidence that genetic factors contribute to the development of thoracic aortic aneurysms (TAA) by demonstrating familial patterns of the disease.Design: Retrospective review.Setting: University hospital.Patients and Methods: We sought to identify familial patterns of TAA from a database of 598 patients evaluated or treated for TAA at the Yale Center for Thoracic Aortic Disease, New Haven, Conn, from January 1985 to August 1998. Of the 598 patients, 45 patients had a diagnosis of Marfan syndrome and 553 patients had no known history of any collagen vascular disorder. Of the 553 patients in the latter category, 398 patients had confirmed TAA, 66 had TAA with concomitant aortic dissections, and 89 had aortic dissections. From the group of 464 patients with TAA with or without concomitant aortic dissections, 2 interviewers attempted to contact 150 randomly selected patients for telephone screening to determine the presence of familial patterns of aortic disease. Fifteen of these patients were lost to follow-up. Complete medical and family histories of the remaining 135 patients (85 men, 50 women) were reviewed. Of the 135 individuals screened, 26 (18 men, 8 women) (19.3%) were found to belong to multiplex pedigrees. These 26 patients with familial nonsyndromic TAA were compared with the remaining 109 patients with sporadic TAA and the 45 patients with Marfan syndrome-associated TAA.Main Outcome Measures: Groups were examined for statistical differences in age and aortic size at the time of diagnosis, growth rates of TAA, and rates of concomitant diseases. Nonsyndromic family pedigrees were analyzed and potential modes of inheritance were determined.Results: The mean age at presentation for patients with familial nonsyndromic TAA (56.8 years) was significantly younger than the mean age of presentation in sporadic cases (64.3 years, P less than or equal to.03), and significantly older than that of patients with Marfan syndrome (24.8 years, P less than or equal to.001). Patients with a family history of aortic aneurysms had faster growth rates (0.22 cm/y) compared with patients with sporadic TAA (0.03 cm/y) (P less than or equal to.001) and patients with Marfan syndrome (0.10 cm/y) (P less than or equal to.04). Familial nonsyndromic TAA in patients with a concomitant aortic dissection had a growth rate of 0.33 cm/y, which was greater than that of patients with sporadic TAA (0.10 cm/y) and patients with Marfan syndrome (0.08 cm/y) with associated aortic dissection. This growth of 0.33 cm/y was significantly faster than the overall growth rate estimate of aneurysms in patients with aortic dissection (0.14 cm/y) (P less than or equal to.05). Ten pedigrees (38.5%) showed direct father to son transmission, consistent with an autosomal dominant mode of inheritance. Six family pedigrees (23.1%) suggested an autosomal dominant or X-linked mode of inheritance. Seven pedigrees (26.9%) suggested a recessive mode of inheritance; 2 an autosomal recessive mode, and 5 an X-linked recessive or autosomal recessive mode. The remaining 3 pedigrees displayed more complex modes of inheritance.Conclusions: This study supports the role of genetic factors influencing familial aggregation of TAA. Thoracic aortic aneurysms in association with multiplex pedigrees represent a new risk factor for aneurysm growth. Pedigree analysis suggests genetic heterogeneity. The primary mode of inheritance seems to be autosomal dominant, but X-linked dominant and recessive modes are also evident.