Generalized epilepsy with febrile seizures plus - A genetic disorder with heterogeneous clinical phenotypes
Generalized epilepsy with febrile seizures plus - A genetic disorder with heterogeneous clinical phenotypes
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DOI：
10.1093/brain/120.3.479
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发表时间：
1997-03-01
期刊：
影响因子：
14.5
通讯作者：
Berkovic, SF
中科院分区：
文献类型：
--
作者：
Scheffer, IE;Berkovic, SF
热性惊厥和全身性癫痫的临床和遗传关系知之甚少。我们确定了一个家庭的家谱信息在2000个人，有一个不寻常的集中的个人与热性惊厥和全身性癫痫的一部分谱系。我们首先阐明了复杂的血缘关系，在较早的几代人，然后系统地研究了癫痫表型在受影响的个人。在一个分支（核心家族）中，超过四代的25个个体受到影响。最常见的表型，表示为“热性惊厥+”（FS+），包括儿童期发作（中位数1年）的多发性热性惊厥，但与典型的热性惊厥综合征不同，发热持续超过6年，或发生无热性惊厥。其他表型包括FS+和失神，FS+和肌阵挛性癫痫发作，FS+和失张力性癫痫发作，最严重的受影响的个体有肌阵挛性-不稳定性癫痫（MAE）。遗传方式为常染色体显性遗传。广泛性癫痫表型的巨大变化不能用后天因素来解释。对这个大家族的分析和对文献的批判性回顾导致了遗传性癫痫综合征的概念，称为全身性癫痫伴热性惊厥（GEFS（+））。GEFS（+）有一系列表型，包括热性惊厥、FS+和不太常见的MAE。GEFS（+）的识别解释了以前认识不足的良性儿童全身性癫痫的癫痫表型。在个别患者中，GEFS（+）的遗传性可能被忽视。分子遗传学研究，这样的大家庭应允许相关的基因鉴定热性惊厥和全身性癫痫。
The clinical and genetic relationships of febrile seizures and the generalized epilepsies are poorly understood. We ascertained a family with genealogical information in 2000 individuals where there was an unusual concentration of individuals with febrile seizures and generalized epilepsy in one part of the pedigree. We first clarified complex consanguineous relationships in earlier generations and then systematically studied the epilepsy phenotypes in affected individuals. In one branch (core family) 25 individuals over four generations were affected The commonest phenotype, denoted as 'febrile seizures plus' (FS+), comprised childhood onset (median 1 year) of multiple febrile seizures, but unlike the typical febrile convulsion syndrome, attacks with fever continued beyond 6 years, or afebrile seizures occurred Seizures usually ceased by mid childhood (median II years). Other phenotypes included FS+ and absences, FS+ and myoclonic seizures, FS+ and atonic seizures, and the most severely affected individual had myoclonic-astatic epilepsy (MAE). The pattern of inheritance was autosomal dominant. The large variation in generalized epilepsy phenotypes was not explained by acquired factors. Analysis of this large family and critical review of the literature led to the concept of a genetic epilepsy syndrome termed generalized epilepsy with febrile seizures phs (GEFS(+)). GEFS(+) has a spectrum of phenotypes including febrile seizures, FS+ and the less common MAE. Recognition of GEFS(+) explains the epilepsy phenotypes of previously poorly understood benign childhood generalized epilepsies. In individual patients the inherited nature of GEFS(+) may be overlooked. Molecular genetic study of such large families should allow identification of genes relevant to febrile seizures and generalized epilepsies.