Department of Child Neuropsychiatry, Children's Hospital, Ancona, Italy.
Department of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital, Rome, Italy.
Epilepsia. 2020 Nov;61(11):2474-2485. doi: 10.1111/epi.16699. Epub 2020 Oct 16.
Autosomal recessive pathogenic variants of the SLC13A5 gene are associated with severe neonatal epilepsy, developmental delay, and tooth hypoplasia/hypodontia. We report on 14 additional patients and compare their phenotypic features to previously published patients to identify the clinical hallmarks of this disorder.
We collected clinical features of 14 patients carrying biallelic variants in SLC13A5 and performed a PubMed search to identify previously published patients.
All patients presented clonic or tonic seizures in the first days of life, evolving into status epilepticus in 57%. Analysis of seizure frequency and developmental milestones divided into five epochs showed an evolutionary trajectory of both items. In the first 3 years of life, 72% of patients had weekly/monthly seizures, often triggered by fever; 14% were seizure-free. Between the ages of 3 and 12 years, 60% become seizure-free; in the following years, up to age 18 years, 57% were seizure-free. After the age of 18 years, all three patients reaching this age were seizure-free. Similarly, 86% of patients at onset presented mild to moderate developmental impairment and diffuse hypotonia. In late childhood, all had developmental delay that was severe in most. Benzodiazepines, phenobarbital, phenytoin, and carbamazepine were the most effective drugs. Eight probands carried heterozygous compound variants, and homozygous pathogenic variants occurred in six. Literature review identified 45 patients carrying SLC13A5 gene pathogenic variants whose clinical features overlapped with our cohort. A peculiar and distinguishing sign is the presence of tooth hypoplasia and/or hypodontia in most patients.
Autosomal recessive pathogenic variants in SLC13A5 are associated with a distinct neonatal epileptic encephalopathy evolving into severe cognitive and motor impairment, yet with seizures that settle down in late childhood. Tooth hypoplasia or hypodontia remains the peculiar feature. The SLC13A5 gene should be screened in neonatal epileptic encephalopathies; its recessive inheritance has relevance for genetic counseling.
常染色体隐性致病性 SLC13A5 基因突变与严重的新生儿癫痫、发育迟缓以及牙齿发育不全/缺如有关。我们报告了另外 14 例患者，并将其表型特征与先前发表的患者进行比较，以确定该疾病的临床特征。
我们收集了 14 例 SLC13A5 双等位基因突变患者的临床特征，并在 PubMed 上进行了检索，以确定以前发表的患者。
所有患者在生命的最初几天均出现强直-阵挛性发作，57%的患者发展为癫痫持续状态。根据发作频率和发育里程碑的分析，分为五个时期，显示出这两个项目的演变轨迹。在生命的前 3 年，72%的患者每周/每月发作，常因发热而诱发；14%的患者无发作。在 3 至 12 岁之间，60%的患者无发作；随后几年，直到 18 岁，57%的患者无发作。18 岁以后，所有达到这一年龄的 3 名患者均无发作。同样，86%的患者在发病时表现出轻度至中度发育障碍和广泛的肌张力低下。在儿童后期，所有人都有严重的发育迟缓。苯二氮䓬类、苯巴比妥、苯妥英和卡马西平是最有效的药物。8 名先证者携带杂合复合变异体，6 名先证者携带纯合致病性变异体。文献回顾确定了 45 名携带 SLC13A5 基因突变的患者，其临床特征与我们的队列重叠。一个特殊且有区别的特征是大多数患者存在牙齿发育不全和/或缺如。
SLC13A5 中的常染色体隐性致病性变异与一种明显的新生儿癫痫性脑病相关，该疾病会发展为严重的认知和运动障碍，但在儿童后期发作会得到控制。牙齿发育不全或缺如是其独特的特征。SLC13A5 基因应在新生儿癫痫性脑病中进行筛查；其隐性遗传对遗传咨询具有重要意义。
