Consanguinity and risk of epilepsy
Consanguinity and risk of epilepsy
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近亲和癫痫风险
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发表时间：
2004
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通讯作者：
R. V. T. Ct
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作者：
R. V. T. Ct
与癫痫的遗传联系与Lennox的双胞胎研究一起建立。1，2进一步的人口研究显示，癫痫的家族聚集性在一级亲属中增加，在较小程度的二级亲属中。32特发性癫痫具有较高的癫痫家族聚集性。3在人群研究中也发现了类似的与隐源性癫痫的关联，特别是对于全面性癫痫和较年轻的癫痫发作。3像顽固性HS和SSEL这样的症状性癫痫，据报道有20-60%的癫痫/癫痫家族史。4，5这种高发病率可能是由于共同的环境或共同的遗传影响。近亲婚姻在一些文化中是可以接受的，而且在繁殖过程中会增加某种特定遗传病的患病表现。我们正在调查父母的血缘关系在患有癫痫的兄弟姐妹和孩子中的作用和癫痫的风险。采访了316名在马来亚大学医学中心和吉隆坡医院就诊的印度裔马来西亚人癫痫患者。构建了有癫痫病史的一级亲属的家系树。排除单次发作病史。先证者的平均年龄为32岁。癫痫起病年龄19岁，病程13年。男性和女性比例相等。先证者有全身性强直阵挛发作(78%)、复杂部分性发作(12%)和意识丧失(7%)。癫痫发作频率平均为每年8次。癫痫发作分为特发性(28%)、隐源性(47%)和远端症状性(25%)。先证者平均有3.7个兄弟姐妹和0.8个孩子。先证者的兄弟姐妹的平均年龄为29岁，孩子的平均年龄为4.4岁。19%的先证者在一级亲属中有癫痫家族史。这些发生在他们的兄弟姐妹(12%)、父母(4%)和孩子(2%)中。兄弟姐妹癫痫的终生患病率为4.2%(N=47/1119)，父母为4.1%(N=22/632)，子女为2.9%(N=7/240)。先证者的父母中大多数(85%，n=22)是父亲。父母近亲婚配率为29.5%。有血缘关系和无血缘关系的先证者在人口学、癫痫症状学和分类方面没有差异。对于特发性和隐性遗传组，有血缘关系的家庭成员的癫痫发生率显著高于无血缘关系的双亲婚姻家庭成员。在特发性癫痫组中，父母近亲结婚的癫痫发生率为9.8%(n=12/123)，而非血亲婚姻的癫痫发生率为3.7%(n=15/4.3；P=0.02，RR=2.5，95%CI：1.2~5.2)。在隐匿性癫痫组中，父母近亲结婚的癫痫发生率为13.3%(28/209)，而非血亲婚姻的癫痫发生率为4%(P=0.001)。在特发性癫痫组中，先证者的兄弟姐妹与父母近亲结婚的癫痫发生率显著升高(P=0.001，RR=5.3，95%CI：1.8~15.3)。在隐性癫痫组中，父母近亲结婚的兄弟姐妹(P=0.000.0 4；RR=2.4，95%CI：1.4~4.9)和子女(P=0.000；RR=8.5，95%CI：2.5 2 8.8)癫痫的发生率显著高于兄弟姐妹(P=0.0 4；RR=2.4，95%CI：1.4~4.9)。父母近亲结婚的特发性癫痫组和隐源性癫痫组的兄弟姐妹患癫痫的相对风险为3.1(95%CI：1.7-5.6)。一级亲属为2.8(95%CI：1.9~4.3，P<；0.001)。在特发性癫痫组中，癫痫发病年龄越小，其兄弟姐妹患癫痫的风险越高(p<；0.001)。总而言之，这项研究表明，有父母近亲婚姻的特发性和隐源性癫痫患者的兄弟姐妹患癫痫的风险增加。那些患有隐源性癫痫的孩子患癫痫的风险也增加了。
Genetic link to epilepsy was established with the twin studies of Lennox.1,2 Further population studies revealed an increased familial clustering of epilepsy among first degree and to a lesser degree second degree relatives.32Idiopathic epilepsy has a higher familial clustering of epilepsy.3 Similar association has been seen for cryptogenic epilepsy also in population studies especially for generalised seizure and younger onset of epilepsy3 Symptomatic epilepsy like intractable HS and SSEL have a reported a family history of seizures/epilepsy of 20-60%.4,5 Such high rates may be due to common environmental or common inherited genetic influences. Consanguineous marriage are acceptable is some cultures and in breeding will increase the disease expression of a particular genetic disease. We are investigating the role of parental consanguinity and the risk of epilepsy among siblings and children of probands with epilepsy. Three hundred and sixteen patients with epilepsy who were Malaysians of Indian origin attending the University Malaya Medical Centre and Kuala Lumpur Hospital were interviewed. The family tree of the first degree relatives with history of epilepsy was constructed. History of single seizures was excluded. The mean age of the probands was 32 years. The age of onset of epilepsy was 19 years and the duration of epilepsy was 13 years. There was equal proportion of male and females. The probands had generalized tonicclonic seizure (78%), complex partial seizure (12%) and loss of consciousness (7%). The mean seizure frequency was 8 per year. The seizures were classifies as idiopathic (28%), cryptogenic (47%) and remote symptomatic (25%). The probands had a mean of 3.7 siblings and 0.8 children. The mean age of the probands’ sibling was 29 years, and age of the children was 4.4 years. Nineteen percent of the probands had a family history of epilepsy in first-degree relatives. These occurred among their siblings (12%), parents (4%), and children (2%). The lifetime prevalence of epilepsy among the sibling was 4.2% (N=47/1119); 4.1% (N=22/632) for the parents, and 2.9% (N=7/240) for the children. Majority (85%, n=22) of the proband’s parents with epilepsy were fathers. Parental consanguineous marriage was 29.5%. There was no difference in the demographics, seizure semiology and classification between the probands with consanguineous and nonconsanguineous parental marriage. For the idiopathic and cryptogenic group, there was significantly higher rate of epilepsy among family members with consanguineous as compared to non-consanguineous parental marriage. For the idiopathic epilepsy group, the rate of epilepsy with consanguineous parental marriage was 9.8% (n=12/123) as compared to 3.7% with nonconsanguineous marriage (n=15/4.3; p=0.02, RR=2.5, 95% CI: 1.2-5.2). For the cryptogenic epilepsy group, the rate of epilepsy with consanguineous parental marriage was 13.3% (n=28/209) as compared to 4% for nonconsanguineous marriage (n=24/586; p=<0.001: RR=3.0, 95% CI: 1.8-5.1). In the idiopathic epilepsy group, the rate of epilepsy among siblings of probands was significant higher with parental consanguineous marriage (p=0.001, RR=5.3, 95% CI: 1.8-15.3). In the cryptogenic epilepsy group, the rate of epilepsy was significantly higher both the siblings (p=0.04; RR=2.4, 95% CI: 1.4-4.9) and children (p=0.000; RR = 8.5, 95% CI: 2.528.8) with parental consanguineous marriage. The relative risk of epilepsy for the siblings of idiopathic and cryptogenic epilepsy groups with parental consanguineous marriage was 3.1 (95%CI: 1.7-5.6). It was 2.8 (95%CI: 1.9-4.3, P<0.001) for their first-degree relatives. In idiopathic epilepsy group, there was higher risk of epilepsy siblings among those with younger age of onset of epilepsy (p<0.001). In conclusion, the study shows an increased risk for epilepsy among siblings of patients with idiopathic and cryptogenic epilepsy that has parental consanguineous marriage. The risk of epilepsy in the children of those with cryptogenic epilepsy was also increased.