Abstract：
OBJECTIVE: PCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy.
METHODS: This retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children\'s Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients.
RESULTS: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)).
CONCLUSIONS: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.
METHODS: This retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children\'s Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients.
RESULTS: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)).
CONCLUSIONS: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.
摘要：
目的：PCDH19基因变异，称为PCDH19聚集性癫痫，代表了癫痫的独特病因。本研究旨在阐明PCDH19聚集性癫痫患儿的临床表现，并探讨其基因型和表型。
方法：这项回顾性研究包括病史，磁共振成像，视频脑电图,2015-2023年北京儿童医院神经内科诊断为PCDH19聚集性癫痫患者的基因分析。进行卡方检验和逻辑回归分析，以研究与患者发育迟缓相关的因素。
结果：在所有30名患者中，癫痫发作的年龄范围为5至61个月（中位数14个月；IQR9.25-22.5个月）。在30名患者中，29名女性，1名男性。观察到一系列癫痫发作和发烧引发的癫痫发作，最常见的癫痫发作类型是双侧强直阵挛性癫痫发作（FBTCS）。15例患者成功控制癫痫发作。不幸的是,1例患者因癫痫突然意外死亡(SUDEP).此外,14例患者有遗传性突变，14有从头突变，1具有遗传性和从头突变，1例男性患者由于体细胞突变导致马赛克成分突变为0.64。在17例患者中发现了发育延迟（56.7％），6例（20％）被诊断为自闭症谱系障碍（ASD）。在17名患者中，9在癫痫发作前经历了发育迟缓，虽然8个最初是正常的，但后来在疾病进展过程中出现了发育迟缓。统计学分析显示,耐药性癫痫是发生发育迟缓的独立危险因素(P=0.020,OR=9.758,95%CI(1.440~66.111))。
结论：在这项研究中，在PCDH19聚集性癫痫中发现了13种新的潜在罕见致病变异。在患者中观察到的临床特征与已知的表型特征一致，我们发现，耐药癫痫患者更容易出现发育迟缓。PCDH19变异患者表型的严重程度从药物反应性癫痫发作到难治性癫痫。
方法：这项回顾性研究包括病史，磁共振成像，视频脑电图,2015-2023年北京儿童医院神经内科诊断为PCDH19聚集性癫痫患者的基因分析。进行卡方检验和逻辑回归分析，以研究与患者发育迟缓相关的因素。
结果：在所有30名患者中，癫痫发作的年龄范围为5至61个月（中位数14个月；IQR9.25-22.5个月）。在30名患者中，29名女性，1名男性。观察到一系列癫痫发作和发烧引发的癫痫发作，最常见的癫痫发作类型是双侧强直阵挛性癫痫发作（FBTCS）。15例患者成功控制癫痫发作。不幸的是,1例患者因癫痫突然意外死亡(SUDEP).此外,14例患者有遗传性突变，14有从头突变，1具有遗传性和从头突变，1例男性患者由于体细胞突变导致马赛克成分突变为0.64。在17例患者中发现了发育延迟（56.7％），6例（20％）被诊断为自闭症谱系障碍（ASD）。在17名患者中，9在癫痫发作前经历了发育迟缓，虽然8个最初是正常的，但后来在疾病进展过程中出现了发育迟缓。统计学分析显示,耐药性癫痫是发生发育迟缓的独立危险因素(P=0.020,OR=9.758,95%CI(1.440~66.111))。
结论：在这项研究中，在PCDH19聚集性癫痫中发现了13种新的潜在罕见致病变异。在患者中观察到的临床特征与已知的表型特征一致，我们发现，耐药癫痫患者更容易出现发育迟缓。PCDH19变异患者表型的严重程度从药物反应性癫痫发作到难治性癫痫。
