PDF(Pubmed)
Abstract：
UNASSIGNED: SLC6A1 is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. SLC6A1-neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population.
UNASSIGNED: Here, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search.
UNASSIGNED: A total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic-clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients.
UNASSIGNED: The phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in >60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts.
UNASSIGNED: Here, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search.
UNASSIGNED: A total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic-clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients.
UNASSIGNED: The phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in >60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts.
摘要：
■SLC6A1是癫痫最常见的单基因原因之一，也是神经发育障碍的公认原因。SLC6A1-神经发育障碍具有轻度至重度智力障碍（ID）的一致表型，癫痫,语言延迟和行为障碍。这种表型描述主要基于儿科人群的知识。
■这里，我们试图通过确定已发表和未发表的患者来描述患有SLC6A1变异且年龄超过18岁的患者.通过国际合作确定了未发表的患者，虽然以前发表的患者是通过文献检索收集的。
■共包括15例SLC6A1变异的成年患者。9/13患者患有中度至重度ID（两个数据不可用）。癫痫很普遍（11/15），癫痫发作类型如缺席，肌阵挛性,atonic,和强直阵挛性癫痫发作。癫痫在7/11难治，而4例患者使用拉莫三嗪无癫痫发作，丙戊酸盐,或拉莫三嗪与丙戊酸盐组合。五名患者的语言发育严重受损。据报道，行为障碍主要包括自闭症谱系障碍和攻击行为。任何患者均未报告精神分裂症。
■此处显示的成年患者的表型类似于患有ID的儿科队列，癫痫,和行为障碍，表明SLC6A1-NDD的表型随着时间的推移是一致的。>60%的癫痫患者癫痫发作难治，表明SLC6A1-NDDs缺乏靶向治疗。随着人们越来越关注药物的再利用和新治疗方法的开发，希望这里反映的前景会随着时间的推移而改变。成年患者的ID似乎更严重，尽管这可能反映了招聘偏见，仅纳入在专业中心就诊的患者,或者这可能是SLC6A1-NDD自然史的特征.这个问题值得在更大的队列中进行进一步的研究。
■这里，我们试图通过确定已发表和未发表的患者来描述患有SLC6A1变异且年龄超过18岁的患者.通过国际合作确定了未发表的患者，虽然以前发表的患者是通过文献检索收集的。
■共包括15例SLC6A1变异的成年患者。9/13患者患有中度至重度ID（两个数据不可用）。癫痫很普遍（11/15），癫痫发作类型如缺席，肌阵挛性,atonic,和强直阵挛性癫痫发作。癫痫在7/11难治，而4例患者使用拉莫三嗪无癫痫发作，丙戊酸盐,或拉莫三嗪与丙戊酸盐组合。五名患者的语言发育严重受损。据报道，行为障碍主要包括自闭症谱系障碍和攻击行为。任何患者均未报告精神分裂症。
■此处显示的成年患者的表型类似于患有ID的儿科队列，癫痫,和行为障碍，表明SLC6A1-NDD的表型随着时间的推移是一致的。>60%的癫痫患者癫痫发作难治，表明SLC6A1-NDDs缺乏靶向治疗。随着人们越来越关注药物的再利用和新治疗方法的开发，希望这里反映的前景会随着时间的推移而改变。成年患者的ID似乎更严重，尽管这可能反映了招聘偏见，仅纳入在专业中心就诊的患者,或者这可能是SLC6A1-NDD自然史的特征.这个问题值得在更大的队列中进行进一步的研究。
