The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disab...The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hype-ractivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a de novo mutation of the CNKSR2 gene(c.2185C >T, p.Arg729Ter) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the CNKSR2 gene has been rarely reported in epilepsy aphasia syndrome, but no de novo mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.展开更多
Background:Landau-Kleffner syndrome(LKS)is an acquired aphasia and electroencephalogram(EEG)abnormalities mainly in temporoparietal areas.SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aq...Background:Landau-Kleffner syndrome(LKS)is an acquired aphasia and electroencephalogram(EEG)abnormalities mainly in temporoparietal areas.SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aqueduct(EVA).Case presentations:We report a case of LKS in a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G(IVS7-2A>G)in SLC26A4.He had normal language development before 2 years old.At the age of 2.5 years,he was admitted to the hospital due to remarkable language delay,and diagnosed with hearing loss with EVA.The seizures started at 4.4 years of age and EEG recording showed electrical status epilepticus during sleep(ESES)with a posterior-temporal predominance.He received cochlear implantation in the right ear at 4.7 years of age,which improved his hearing and language skills.The nocturnal focal motor seizures recurred at 4.9 years of age.Then a remarkable inability to respond to calls and reduction in spontaneous speech were noticed.He was treated with methylprednisolone at 5 years old,which controlled the seizures,suppressed ESES,and remarkably improved the language ability.The absence of seizures maintained until the last follow-up at 5.3 years of age,with further improvements in EEG recording and language ability.Conclusions:The co-existence of LKS and hearing loss caused by SLC26A4 mutations increases the difficulty of LKS diagnosis,especially in the presence of hearing loss and impaired language skills.EEG discharges predominantly in temporoparietal areas,the occurrence of ESES,and language improvement after antiepileptic medications are potential indicators for LKS diagnosis.展开更多
目的探讨癫痫失语疾病谱（epilepsy—aphasia spectrum，EAS）患JLGRIN2A基因的突变率及临床遗传学特点。方法以Landau—Kleffner综合征（Landau-Kleffner syndrome，LKs）、癫痫伴慢波睡眠期持续棘慢波（epilepsy with continuous spik...目的探讨癫痫失语疾病谱（epilepsy—aphasia spectrum，EAS）患JLGRIN2A基因的突变率及临床遗传学特点。方法以Landau—Kleffner综合征（Landau-Kleffner syndrome，LKs）、癫痫伴慢波睡眠期持续棘慢波（epilepsy with continuous spikes and waves during slow sleep，CSWS）、儿童良性癫痫伴中央颞区棘波（benign childhood epilepsy with centrotemporal spikes，BECT）及BECT变异型患儿为研究对象，采用Sanger测序法筛查GRIN2A基因的突变，并分析EAS患儿的临床遗传学特点。结果共收集到122例EAS患儿，包括9例LKS、26例CSWS、42例BECT变异型及45例BECT。该组患儿癫痫发作或失语的平均起病年龄为5岁（10个月至11岁）。GRIN2A突变筛查在4例无血缘关系的患儿中分别发现了1个可能致病的错义突变，包括c．2278G〉A（p．G760S）、C．4153G〉T（P．D1385Y）、C．1364G〉A（p．C455Y）和C．691T〉C（p．C231R），其中1例为LKS，其余3例为BECT变异型。GRIN2A在LKS和BECT变异型中的突变率分别为11．1％（1／9）和7．2％（3／42），而在26例CSWS及45例BECT患儿则均未发现突变。在122例患儿中，25例（20．5％）有热性惊厥或癫痫阳性家族史，但均未携带GRIN2A突变。结论EAS患儿可携带GRIN2A基因突变，但突变率相对较低。GRIN2A突变阴性的患儿中家族史为阳性者占一定的比例，提示EAS可能具有复杂的遗传学机制。展开更多
睡眠中癫痫性电持续状态（electrical status epilepticus during sleep，ESES）作为一种特殊的脑电现象与癫痫发作、语言及认知障碍、行为异常等临床表现相关。具有ESES特征的癫痫综合征包括：Landau-Kleffner综合征（LKS）、儿童良性...睡眠中癫痫性电持续状态（electrical status epilepticus during sleep，ESES）作为一种特殊的脑电现象与癫痫发作、语言及认知障碍、行为异常等临床表现相关。具有ESES特征的癫痫综合征包括：Landau-Kleffner综合征（LKS）、儿童良性癫痫伴中央颞区棘波（benign childhood epilepsy with centrotemporal spikes，展开更多
基金Supported by Jining Medical University,No.JYP201740
文摘The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hype-ractivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a de novo mutation of the CNKSR2 gene(c.2185C >T, p.Arg729Ter) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the CNKSR2 gene has been rarely reported in epilepsy aphasia syndrome, but no de novo mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.
基金This work was supported by grants from the National Natural Science Foundation of China(81771393 and 82171436)Beijing Natural Science Foundation(7202210)Capital Funds for Health Improvement and Research(2020-2-4077).
文摘Background:Landau-Kleffner syndrome(LKS)is an acquired aphasia and electroencephalogram(EEG)abnormalities mainly in temporoparietal areas.SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aqueduct(EVA).Case presentations:We report a case of LKS in a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G(IVS7-2A>G)in SLC26A4.He had normal language development before 2 years old.At the age of 2.5 years,he was admitted to the hospital due to remarkable language delay,and diagnosed with hearing loss with EVA.The seizures started at 4.4 years of age and EEG recording showed electrical status epilepticus during sleep(ESES)with a posterior-temporal predominance.He received cochlear implantation in the right ear at 4.7 years of age,which improved his hearing and language skills.The nocturnal focal motor seizures recurred at 4.9 years of age.Then a remarkable inability to respond to calls and reduction in spontaneous speech were noticed.He was treated with methylprednisolone at 5 years old,which controlled the seizures,suppressed ESES,and remarkably improved the language ability.The absence of seizures maintained until the last follow-up at 5.3 years of age,with further improvements in EEG recording and language ability.Conclusions:The co-existence of LKS and hearing loss caused by SLC26A4 mutations increases the difficulty of LKS diagnosis,especially in the presence of hearing loss and impaired language skills.EEG discharges predominantly in temporoparietal areas,the occurrence of ESES,and language improvement after antiepileptic medications are potential indicators for LKS diagnosis.
文摘目的探讨癫痫失语疾病谱（epilepsy—aphasia spectrum，EAS）患JLGRIN2A基因的突变率及临床遗传学特点。方法以Landau—Kleffner综合征（Landau-Kleffner syndrome，LKs）、癫痫伴慢波睡眠期持续棘慢波（epilepsy with continuous spikes and waves during slow sleep，CSWS）、儿童良性癫痫伴中央颞区棘波（benign childhood epilepsy with centrotemporal spikes，BECT）及BECT变异型患儿为研究对象，采用Sanger测序法筛查GRIN2A基因的突变，并分析EAS患儿的临床遗传学特点。结果共收集到122例EAS患儿，包括9例LKS、26例CSWS、42例BECT变异型及45例BECT。该组患儿癫痫发作或失语的平均起病年龄为5岁（10个月至11岁）。GRIN2A突变筛查在4例无血缘关系的患儿中分别发现了1个可能致病的错义突变，包括c．2278G〉A（p．G760S）、C．4153G〉T（P．D1385Y）、C．1364G〉A（p．C455Y）和C．691T〉C（p．C231R），其中1例为LKS，其余3例为BECT变异型。GRIN2A在LKS和BECT变异型中的突变率分别为11．1％（1／9）和7．2％（3／42），而在26例CSWS及45例BECT患儿则均未发现突变。在122例患儿中，25例（20．5％）有热性惊厥或癫痫阳性家族史，但均未携带GRIN2A突变。结论EAS患儿可携带GRIN2A基因突变，但突变率相对较低。GRIN2A突变阴性的患儿中家族史为阳性者占一定的比例，提示EAS可能具有复杂的遗传学机制。
文摘睡眠中癫痫性电持续状态（electrical status epilepticus during sleep，ESES）作为一种特殊的脑电现象与癫痫发作、语言及认知障碍、行为异常等临床表现相关。具有ESES特征的癫痫综合征包括：Landau-Kleffner综合征（LKS）、儿童良性癫痫伴中央颞区棘波（benign childhood epilepsy with centrotemporal spikes，
