Familial thoracic aortic aneurysms and dissections - Incidence, modes of inheritance, and phenotypic patterns
Familial thoracic aortic aneurysms and dissections - Incidence, modes of inheritance, and phenotypic patterns
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DOI：
10.1016/j.athoracsur.2006.04.098
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发表时间：
2006-10-01
影响因子：
4.6
通讯作者：
Elefteriades, John A.
中科院分区：
文献类型：
--
作者：
Albornoz, Gonzalo;Coady, Michael A.;Elefteriades, John A.
背景。我们研究了大量患者的胸主动脉瘤（TAAs）和夹层的遗传性质和表型特征。对520名TAAs患者进行了访谈，并编制了他们的谱系，以确定患有动脉瘤的家庭成员。研究患者分为三组：88个家系中101例有TAA家族型（家族型），369例无家族型（散发性），50例有马凡氏综合征（MFS）。我们确定了家族聚类的发生率、发病年龄、动脉瘤生长率、高血压发病率、亲属间动脉瘤位置的相关性以及系谱遗传模式。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达性。家族性TAA组明显比散发性TAA组年轻（p < 0.0001），但不如MFS组年轻（p < 0.0001）（平均年龄，58.2岁对65.7岁对27.4岁）。197例动脉瘤先证及亲属中，TAA 131例（66.5%），腹主动脉瘤49例（24.9%），脑及其他动脉瘤17例（8.6%）。升动脉瘤最常与升动脉瘤配对，降动脉瘤与腹动脉瘤配对。腹主动脉瘤（AAAs）和高血压与下行TAAs的相关性高于上行TAAs （p < 0.001）。主动脉生长速率以家族性组最高（0.21cm/y），散发性组居中（0.16 cm/y），马凡组最低（0.1 cm/y, p < 0.01）。TAAs通常是家族性疾病。遗传的主要模式是常染色体显性。家族性taa发病年龄相对较早。亲属动脉瘤可见于胸主动脉、腹主动脉或脑循环。筛查TAA先证者的一级亲属是必要的。家族性taa倾向于以更高的速度增长，这是一种更具侵略性的临床实体。
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 ( 0.21cm/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.