Department of Medicine, Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Section of Neurology, Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Epilepsia. 2017 Jun;58(6):1085-1094. doi: 10.1111/epi.13746. Epub 2017 Apr 25.
This study was designed to describe the spectrum of epilepsy phenotypes in Koolen-de Vries syndrome (KdVS), a genetic syndrome involving dysmorphic features, intellectual disability, hypotonia, and congenital malformations, that occurs secondary to 17q21.31 microdeletions and heterozygous mutations in KANSL1.
We were invited to attend a large gathering of individuals with KdVS and their families. While there, we recruited individuals with KdVS and seizures, and performed thorough phenotyping. Additional subjects were included who approached us after the family support group brought attention to our research via social media. Inclusion criteria were genetic testing results demonstrating 17q21.31 deletion or KANSL1 mutation, and at least one seizure.
Thirty-one individuals were studied, aged 2-35 years. Median age at seizure onset was 3.5 years, and 9 of 22 had refractory seizures 2 years after onset. Focal impaired awareness seizures were the most frequent seizure type occurring in 20 of 31, usually with prominent autonomic features. Twenty-one patients had prolonged seizures and, at times, refractory status epilepticus. Electroencephalography (EEG) showed focal/multifocal epileptiform discharges in 20 of 26. MRI studies of 13 patients were reviewed, and all had structural anomalies. Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common, although periventricular nodular heterotopia, focal cortical dysplasia, abnormal sulcation, and brainstem and cerebellum abnormalities were also observed. One patient underwent epilepsy surgery for a lesion that proved to be an angiocentric glioma.
The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence.
本研究旨在描述 Koolen-de Vries 综合征（KdVS）的癫痫表型谱，KdVS 是一种遗传性综合征，表现为畸形特征、智力障碍、肌张力减退和先天性畸形，继发于 17q21.31 微缺失和 KANSL1 杂合突变。
我们应邀参加了一个有 KdVS 患者及其家属参加的大型聚会。在那里，我们招募了有 KdVS 和癫痫发作的患者，并进行了详细的表型分析。还纳入了一些在家族支持团体通过社交媒体引起我们的研究关注后主动联系我们的患者。纳入标准为基因检测结果显示 17q21.31 缺失或 KANSL1 突变，以及至少有一次癫痫发作。
共研究了 31 名患者，年龄 2-35 岁。癫痫发作的中位年龄为 3.5 岁，22 例中有 9 例在发病 2 年后出现难治性癫痫发作。局灶性意识障碍性癫痫发作是最常见的癫痫发作类型，发生在 31 例中的 20 例，通常伴有明显的自主神经特征。21 例患者有长时间的癫痫发作，有时还伴有难治性癫痫持续状态。26 例中的 20 例进行了脑电图（EEG）检查，显示局灶性/多灶性癫痫样放电。回顾了 13 例患者的 MRI 研究，均存在结构异常。胼胝体发育不良、海马异常和脑室扩张最常见，但也观察到脑室周围结节性异位、局灶性皮质发育不良、异常脑回和脑干、小脑异常。1 例患者因病变行癫痫手术，证实为血管中心性胶质瘤。
KdVS 的典型癫痫表型包括儿童期起病的局灶性癫痫发作，持续时间长，伴有明显的自主神经特征。多灶性癫痫样放电是典型的脑电图模式。结构脑异常可能是普遍存在的，包括异常神经母细胞迁移和异常轴突导向的迹象。鉴于广泛的神经解剖异常，应谨慎进行癫痫手术；然而，肿瘤是一种罕见但重要的发生情况。
