Nakken K O, Magnusson A, Steinlein O K
The National Center for Epilepsy, Sandvika, Norway.
Epilepsia. 1999 Jan;40(1):88-92. doi: 10.1111/j.1528-1157.1999.tb01993.x.
The aim of the study was to describe in detail the electroclinical findings associated with a mutation in the acetylcholine receptor in a Norwegian family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Furthermore, we compared the clinical features associated with this mutation with those of an Australian family with a different mutation at the same locus, as well as with those of eight Italian families with ADNFLE and without a verified mutation in this gene.
We obtained medical records from all of the 10 known affected members of the Norwegian family. A personal interview and a clinical neurologic examination were carried out in six of them. Interictal and ictal scalp EEG recordings were obtained in eight and three, respectively, computed tomography/magnetic resonance imaging (CT/MRI) in five, and blood samples for genetic analysis in seven individuals. The clinical features after an insertion of a leucine residue in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor are examined. Furthermore, the clinical features that accompany this insertion and the clinical features associated with a missense mutation (Ser248Phe) in the same gene were compared.
All the affected individuals had a seizure semiology consistent with frontal lobe seizures. Their seizures started in childhood (mean age, 8 years) and were often misinterpreted as benign nocturnal parasomnias, nocturnal paroxysmal dystonia, or a psychiatric disorder. The affected family members were of normal intellect and showed no abnormalities at neurologic and neuroradiologic examinations. Interictal scalp EEG registrations were mostly normal, ictal scalp EEG registrations in three individuals revealed left frontal low-voltage epileptiform discharges in two, and only shallow arousal preceding the attack in one. Although the seizure susceptibility varied among the affected individuals, the epilepsy course was mostly benign.
Patients with ADNFLE, either with the 776ins3 mutation or the Ser248Phe mutation, and those without any recognized mutation in the acetylcholine receptor, have strikingly homogeneous phenotypes, and it seems difficult to separate them on clinical grounds.
本研究旨在详细描述一个患有常染色体显性遗传性夜间额叶癫痫（ADNFLE）的挪威家族中，与乙酰胆碱受体突变相关的电临床特征。此外，我们将该突变相关的临床特征与一个在同一基因座有不同突变的澳大利亚家族，以及八个患有ADNFLE但该基因未证实有突变的意大利家族的临床特征进行了比较。
我们获取了挪威家族中所有10名已知患病成员的病历。其中6人接受了个人访谈和临床神经学检查。分别对8人和3人进行了发作间期和发作期头皮脑电图记录，5人进行了计算机断层扫描/磁共振成像（CT/MRI），7人采集了血样用于基因分析。研究了神经元烟碱型乙酰胆碱受体α4亚基中插入一个亮氨酸残基后的临床特征。此外，还比较了伴随此插入的临床特征以及同一基因中错义突变（Ser248Phe）相关的临床特征。
所有患病个体的发作症状学均与额叶癫痫相符。他们的癫痫发作始于儿童期（平均年龄8岁），常被误诊为良性夜间睡眠障碍、夜间阵发性肌张力障碍或精神疾病。患病家庭成员智力正常，神经学和神经放射学检查未发现异常。发作间期头皮脑电图记录大多正常，3名个体的发作期头皮脑电图记录显示，2人左侧额叶有低电压癫痫样放电，1人仅在发作前有浅觉醒。尽管患病个体的癫痫易感性有所不同，但癫痫病程大多为良性。
患有ADNFLE的患者，无论是携带776ins3突变还是Ser248Phe突变，以及那些乙酰胆碱受体未发现任何公认突变的患者，其表型都非常相似，似乎很难基于临床特征将他们区分开来。
