Abstract：
OBJECTIVE: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.
METHODS: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
CONCLUSIONS: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
METHODS: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
CONCLUSIONS: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
摘要：
目的：KCTD7相关的进行性肌阵挛性癫痫（PME）是一种罕见的常染色体隐性遗传疾病。这项研究旨在描述一个大型国际队列中的临床细节和遗传变异。
方法：通过国际合作确定了与KCTD7相关的PME分子确诊的家族。此外，我们进行了系统审查,以确定以前报告的病例.显著的人口统计，癫痫,治疗,基因检测,脑电图（EEG），收集和总结影像相关变量.
结果：纳入42例患者（36个家庭）。首次发作的中位年龄为14个月（四分位距=11.75-22.5）。肌阵挛性癫痫发作通常是注意到的第一癫痫发作类型(n=18,43.9%)。脑电图和脑磁共振成像的发现是可变的。许多患者表现出发育延迟，随后逐渐消退（n=16，38.1%）。21例（55％）的基因检测以前报道过KCTD7变异，17例（45％）的KCTD7基因有新的变异。该队列中有6名患者死亡（年龄范围=1.5-21岁）。系统评价确定了23项符合条件的研究，并从文献中进一步确定了59例以前报道的KCTD7相关疾病。大多数报告病例的表型与PME一致(n=52,88%)。文献中报道的其他表型包括视阵肌阵挛性共济失调综合征（n=2），肌张力障碍（n=2），和神经元类脂褐素病（n=3）。八例已发表的病例随着时间的推移而死亡(14%，年龄范围=3-18岁)。
结论：本研究队列和系统评价合并了KCTD7相关疾病的表型谱和自然史。早发性耐药癫痫,无情的神经回归，严重的神经系统后遗症很常见。更好地了解自然史可能有助于未来的临床试验。
方法：通过国际合作确定了与KCTD7相关的PME分子确诊的家族。此外，我们进行了系统审查,以确定以前报告的病例.显著的人口统计，癫痫,治疗,基因检测,脑电图（EEG），收集和总结影像相关变量.
结果：纳入42例患者（36个家庭）。首次发作的中位年龄为14个月（四分位距=11.75-22.5）。肌阵挛性癫痫发作通常是注意到的第一癫痫发作类型(n=18,43.9%)。脑电图和脑磁共振成像的发现是可变的。许多患者表现出发育延迟，随后逐渐消退（n=16，38.1%）。21例（55％）的基因检测以前报道过KCTD7变异，17例（45％）的KCTD7基因有新的变异。该队列中有6名患者死亡（年龄范围=1.5-21岁）。系统评价确定了23项符合条件的研究，并从文献中进一步确定了59例以前报道的KCTD7相关疾病。大多数报告病例的表型与PME一致(n=52,88%)。文献中报道的其他表型包括视阵肌阵挛性共济失调综合征（n=2），肌张力障碍（n=2），和神经元类脂褐素病（n=3）。八例已发表的病例随着时间的推移而死亡(14%，年龄范围=3-18岁)。
结论：本研究队列和系统评价合并了KCTD7相关疾病的表型谱和自然史。早发性耐药癫痫,无情的神经回归，严重的神经系统后遗症很常见。更好地了解自然史可能有助于未来的临床试验。
