目的:本研究报告了中国首例Kohlschütter-Tönz综合征(KTS),并对报告病例进行了文献复习。
方法:患者在重庆医科大学附属儿童医院登记。详细记录患者的症状和治疗情况,病人被监测了六年。我们在搜索策略中采用了以下搜索词和布尔运算符的组合:Kohlschütter-Tönz综合征,KTS,还有ROGDI.这些术语经过精心选择,以捕获PubMed中广泛的相关出版物,WebofScience,世卫组织全球卫生图书馆,和中国国家知识基础设施,包括同义词,变体,以及与KTS相关的特定术语。使用SpleeAI和MutationTaster预测变体的致病性,使用I-TASSER构建ROGDI突变的结构。
结果:这是中国首例KTS病例报告。我们的病人出现了癫痫,全球发育迟缓,和牙釉质发育不全。三个WES揭示了ROGDI中的纯合突变(c.46-37_46-30del)。脑磁共振成像(MRI)和视频脑电图(VEEG)均正常。perampanel(PMP)治疗癫痫发作和智力障碍的疗效很明显。此外,检索到43例ROGDI相关KTS。100%出现癫痫,全球发育迟缓,和牙釉质发育不全。17.2%的人被诊断为注意力缺陷多动障碍(ADHD),3.4%的人怀疑患有自闭症谱系障碍(ASD)。所有患者均出现语言障碍。情绪障碍,尤其是自我伤害行为(9.1%),也有报道。
结论:与ROGDI相关的KTS是一种罕见的神经退行性疾病,以三种经典临床表现为特征:癫痫,全球发育迟缓,和牙釉质发育不全。此外,患者可能会出现合并症,包括多动症,ASD,情绪障碍,和语言障碍。PMP可能是一种疗效相对较好的潜在药物,但仍需要长期的临床试验。
This study reported the first
case of Kohlschütter-Tönz syndrome (KTS) in China and reviewed the literature of the reported cases.
This patient was registered at the Children\'s Hospital of Chongqing Medical University. The patient\'s symptoms and treatments were recorded in detail, and the patient was monitored for six years. We employed a combination of the following search terms and Boolean operators in our search strategy: Kohlschütter-Tönz syndrome, KTS, and ROGDI. These terms were carefully selected to capture a broad range of relevant publications in PubMed, Web of Science, WHO Global Health Library, and China National Knowledge Infrastructure, including synonyms, variations, and specific terms related to KTS. The pathogenicity of the variants was predicted using SpliceAI and MutationTaster, and the structures of the ROGDI mutations were constructed using I-TASSER.
This is the first
case report of KTS in China. Our patient presented with epilepsy, global developmental delay, and amelogenesis imperfecta. A trio-WES revealed homozygous mutations in ROGDI (c.46-37_46-30del). The brain magnetic resonance imaging (MRI) and video electroencephalogram (VEEG) were normal. The efficacy of perampanel (PMP) in treating seizures and intellectual disability was apparent. Furthermore, 43 cases of ROGDI-related KTS were retrieved. 100% exhibited epilepsy, global developmental delay, and amelogenesis imperfecta. 17.2% received a diagnosis of attention deficit hyperactivity disorder (ADHD), and 3.4% were under suspicion of autism spectrum disorder (ASD). Language disorders were observed in all patients. Emotional disorders, notably self-harm behaviors (9.1%), were also reported.
ROGDI-related KTS is a rare neurodegenerative disorder, characterized by three classic clinical manifestations: epilepsy, global developmental delay, and amelogenesis imperfecta. Moreover, patients could present comorbidities, including ADHD, ASD, emotional disorders, and language disorders. PMP may be a potential drug with relatively good efficacy, but long-term clinical trials are still needed.