家族性胸主动脉瘤和夹层——发病率、遗传模式及表型特征

Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns.

作者信息

Albornoz Gonzalo, Coady Michael A, Roberts Michele, Davies Ryan R, Tranquilli Maryann, Rizzo John A, Elefteriades John A

机构信息

Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.

出版信息

Ann Thorac Surg. 2006 Oct;82(4):1400-5. doi: 10.1016/j.athoracsur.2006.04.098.

DOI:10.1016/j.athoracsur.2006.04.098

PMID:16996941

Abstract

BACKGROUND

We examined the genetic nature and phenotypic features of thoracic aortic aneurysms (TAAs) and dissections in a large cohort of patients.

METHODS

Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had Marfan syndrome (MFS). We determined incidence of familial clustering, age at presentation, rate of aneurysm growth, incidence of hypertension, correlation of aneurysm sites among kindred, and pedigree inheritance patterns.

RESULTS

An inherited pattern for TAA was present in 21.5% of non-MFS patients. The predominant inheritance pattern was autosomal dominant (76.9%), with varying degrees of penetrance and expressivity. The familial TAA group was significantly younger than the sporadic group (p < 0.0001), but not as young as the MFS group (p < 0.0001) (mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197 probands and kindred with aneurysm, 131 (66.5%) had TAA, 49 (24.9%) had abdominal aortic aneurysm (AAA), and 17 (8.6%) had cerebral or other aneurysms. Ascending aneurysm paired most commonly with ascending, and descending with abdominal. Abdominal aortic aneurysms (AAAs) and hypertension were more often associated with descending than with ascending TAAs (p < 0.001). Aortic growth rate was highest for the familial group (0.21 cm/y), intermediate for the sporadic group (0.16 cm/y), and lowest for the Marfan group (0.1 cm/y; p < 0.01).

CONCLUSIONS

TAAs are frequently familial diseases. The predominant mode of inheritance is autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms in relatives may be seen in the thoracic aorta, the abdominal aorta, or the cerebral circulation. Screening of first-order relatives of probands with TAA is essential. Familial TAAs tend to grow at a higher rate, exemplifying a more aggressive clinical entity.

摘要

背景

我们在一大群患者中研究了胸主动脉瘤（TAA）和主动脉夹层的遗传本质及表型特征。

方法

对520例TAA患者进行访谈并编制其家系图谱，以识别患有动脉瘤的家庭成员。研究患者分为三组：88个家系中的101例非马凡综合征患者呈现出TAA的家族模式（家族性组），369例无家族模式（散发性组），50例患有马凡综合征（MFS）。我们确定了家族聚集发生率、发病年龄、动脉瘤生长速率、高血压发生率、亲属间动脉瘤部位的相关性以及家系遗传模式。

结果

21.5%的非MFS患者存在TAA的遗传模式。主要遗传模式为常染色体显性遗传（76.9%），具有不同程度的外显率和表现度。家族性TAA组显著比散发性组年轻（p<0.0001），但不如MFS组年轻（p<0.0001）（平均年龄分别为58.2岁、65.7岁和27.4岁）。在所有197例患有动脉瘤的先证者及其亲属中，131例（66.5%）患有TAA，49例（24.9%）患有腹主动脉瘤（AAA），17例（8.6%）患有脑动脉瘤或其他动脉瘤。升主动脉瘤最常与升主动脉瘤配对，降主动脉瘤最常与腹主动脉瘤配对。腹主动脉瘤（AAA）和高血压与降主动脉TAA的关联比与升主动脉TAA更常见（p<0.001）。家族性组的主动脉生长速率最高（0.21 cm/年），散发性组次之（0.16 cm/年），马凡组最低（0.1 cm/年；p<0.01）。