Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Cerebrovasc Dis. 2012;33(5):466-70. doi: 10.1159/000337035. Epub 2012 Apr 11.
BACKGROUNDAND PURPOSE: The etiology of spontaneous cervical artery dissection (CeAD) is poorly understood in most patients. Mild cervical trauma preceding the dissection event is a common finding, but many CeAD occur spontaneously. It is likely that genetic factors may increase the risk for CeAD. However, familial cases are excedingly rare. Familial clustering of CeAD may be accidental or associated with genetic or environmental risk factors shared between affected relatives. In this explorative study, we aim to show that specific risk factors for familial CeAD exist.
Age of onset, sex, affected artery and number of recurrent CeAD were documented for familial patients and compared with published findings from patients with sporadic CeAD. Concordance of age, sex and dissected artery within the families was analyzed by correlation analysis and by analysis of variance or Kruskal-Wallis testing.
The study sample consisted of 9 new patients with a family history of CeAD enrolled in the Neurology Department of the University of Heidelberg or referred to Heidelberg from other centers. The study sample also included published findings from another 23 patients, in total 32 patients. The mean age of the patients with familial CeAD at their first dissections was 38.4 ± 13.3 years. Twenty (62.5%) patients were female and 12 patients (37.5%) suffered multiple dissections. Four patients (12.5%) presented with recurrent dissections after >1 year. Patients with a familial history of CeAD were younger (p = 0.023) and presented more often with multiple dissections (p = 0.024) and recurrent dissections (p = 0.018). Age at the first event (correlation analysis p = 0.026; analysis of variance p = 0.029) and site of the dissection (correlation analysis p = 0.032; Kruskal-Wallis test p = 0.018) differed between the families, and there was no concordance of gender of affected family members (correlation analysis p = 0.500; Kruskal-Wallis test p = 0.211).
The high prevalence of multiple dissection events and of long-term (>1 year) recurrent dissections in patients with a familial history of CeAD indicates that a specific predisposition for familial CeAD exists. Since age of onset and affected vessel differ between families, the risk profile for familial CeAD is heterogeneous. A large-scale (whole exome) sequencing analysis of 14 patients from 7 of the analyzed families is currently being performed in order to identify causative genetic variants.
大多数患者自发性颈内动脉夹层（CeAD）的病因仍不清楚。在夹层事件发生之前，轻微的颈部创伤是一种常见的发现，但许多 CeAD 是自发发生的。遗传因素可能会增加 CeAD 的风险。然而，家族性病例极为罕见。CeAD 的家族聚集可能是偶然的，也可能与受影响亲属之间共同的遗传或环境风险因素有关。在这项探索性研究中，我们旨在表明存在特定的家族性 CeAD 危险因素。
记录家族性患者的发病年龄、性别、受累动脉和复发性 CeAD 的数量，并与散发性 CeAD 患者的已发表发现进行比较。通过相关性分析和方差分析或 Kruskal-Wallis 检验分析家族内年龄、性别和夹层动脉的一致性。
研究样本包括 9 名新诊断为 CeAD 且有家族史的患者，他们在海德堡大学神经病学系就诊或由其他中心转诊至海德堡，同时也纳入了另一项研究中 23 名患者的已发表发现，共计 32 名患者。家族性 CeAD 患者首次发病时的平均年龄为 38.4±13.3 岁。20 名（62.5%）患者为女性，12 名（37.5%）患者发生多次夹层。4 名（12.5%）患者在首次发病 1 年后复发。有家族性 CeAD 病史的患者更年轻（p=0.023），且更常发生多次夹层（p=0.024）和复发性夹层（p=0.018）。首次发病年龄（相关性分析 p=0.026；方差分析 p=0.029）和夹层部位（相关性分析 p=0.032；Kruskal-Wallis 检验 p=0.018）在家族间存在差异，受累家族成员的性别无一致性（相关性分析 p=0.500；Kruskal-Wallis 检验 p=0.211）。
有家族性 CeAD 病史的患者中多次夹层事件和长期（>1 年）复发性夹层的高发生率表明存在特定的家族性 CeAD 易感性。由于家族间发病年龄和受累血管不同，家族性 CeAD 的风险特征存在异质性。目前正在对 7 个分析家族中的 14 名患者进行全外显子组测序分析，以确定致病的遗传变异。
