Clinical genetic study of the epilepsy-aphasia spectrum
Clinical genetic study of the epilepsy-aphasia spectrum
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DOI：
10.1111/epi.12065
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发表时间：
2013-02-01
期刊：
影响因子：
5.6
通讯作者：
Scheffer, Ingrid E.
中科院分区：
文献类型：
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作者：
Tsai, Meng-Han;Vears, Danya F.;Scheffer, Ingrid E.
目的分析癫痫-失语谱系（EAS）先证癫痫患者发作家族史的频率和性质，以了解这类疾病的遗传结构。方法招募伴有睡眠时持续峰波性脑病（ECSWS）、Landau-Kleffner综合征（LKS）、非典型良性部分性癫痫（ABPE）和中度癫痫-失语障碍（IEAD）的癫痫性脑病患者。所有受影响和可用的未受影响的亲属高达三度的亲缘关系进行表型分析，使用有效的癫痫发作问卷。所有家庭都建立了系谱。根据各亲缘程度计算受影响亲属的比例。分析近亲属癫痫表型。使用相同的方法将这些数据与患有良性儿童癫痫伴中央颞叶尖峰（BECTS）的先证家庭进行比较。共招募31名先证者，包括5名ECSWS， 3名LKS， 1名ABPE和22名IEAD。癫痫发作的平均年龄为3.9岁（范围0.57岁）。男性占优势（68%,21/31）。31例患者中有16例（51.6%）有癫痫家族史。1254名亲属中有癫痫发作史的30人（2.4%），其中一级亲属128人中有13人（10.2%），二级亲属291人中有5人（1.7%），三级亲属835人中有12人（1.4%）。13人有热性发作，其中2人同时有热性发作和癫痫。19例癫痫亲属中，4例为BECTS， 4例为局灶性不明原因癫痫，3例为IEAD， 7例为未分类癫痫。其中一人患有遗传性全身性癫痫。在BECTS先证家庭中，9.8%的一级亲属、3%的二级亲属和1.5%的三级亲属有癫痫发作，这与EAS队列家庭没有显著差异。先证EAS患者亲属癫痫发作的频率表明，EAS的潜在遗传影响与复杂遗传一致，与BECTS相似。在受影响的亲属中观察到的表型模式主要包括发热性癫痫发作和局灶性癫痫发作。这些发现表明，局灶性癫痫的共同遗传易感性是癫痫-失语症谱系的基础。
Purpose To characterize the frequency and nature of the family history of seizures in probands with epilepsy falling within the epilepsy-aphasia spectrum (EAS) in order to understand the genetic architecture of this group of disorders. Methods Patients with epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), Landau-Kleffner syndrome (LKS), atypical benign partial epilepsy (ABPE), and intermediate epilepsy-aphasia disorders (IEAD) were recruited. All affected and available unaffected relatives up to three degrees of relatedness underwent phenotyping using a validated seizure questionnaire. Pedigrees were constructed for all families. The proportion of affected relatives according to each degree of relatedness was calculated. The epilepsy phenotypes in close relatives were analyzed. The data were compared to the families of probands with benign childhood epilepsy with centrotemporal spikes (BECTS) using the same methodology. Key Findings Thirty-one probands, including five ECSWS, three LKS, one ABPE, and 22 IEAD were recruited. The mean age of seizure onset was 3.9 (range 0.57) years. A male predominance was seen (68%, 21/31) . Sixteen (51.6%) of 31 had a positive family history of seizures. Among 1,254 relatives, 30 (2.4%) had a history of seizures: 13 (10.2%) of 128 first-degree relatives, 5 (1.7%) of 291 second-degree relatives, and 12 (1.4%) of 835 third-degree relatives. Thirteen had febrile seizures, including two who had both febrile seizures and epilepsy. Of the 19 relatives with epilepsy, 4 had BECTS, 4 epilepsies with focal seizures of unknown cause, 3 IEAD, and 7 unclassified. One had genetic generalized epilepsy. In the families of the BECTS probands, 9.8% of first-degree, 3% of second-degree, and 1.5% of third-degree relatives had seizures, which was not significantly different from the EAS cohort families. Significance The frequencies of seizures in relatives of probands with EAS suggest that the underlying genetic influence of EAS is consistent with complex inheritance and similar to BECTS. The phenotypic pattern observed in the affected relatives comprised predominantly febrile seizures and focal seizures. These findings suggest that a shared genetic predisposition to focal epilepsies underpins the epilepsy-aphasia spectrum.