Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum
Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum
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DOI：
10.1016/j.braindev.2017.08.003
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发表时间：
2018-02-01
影响因子：
1.7
通讯作者：
Saitoh, Shinji
中科院分区：
文献类型：
--
作者：
Nakamura, Yuji;Togawa, Yasuko;Saitoh, Shinji
2013年首次报道SZT 2突变是早发性癫痫性脑病的原因。由于迄今为止仅发表了5篇报告，因此与SZT 2相关的临床特征仍不清楚。我们在此报告一个额外的病人与双等位基因突变SZT 2。先证者是一名4岁的女孩，从2岁开始表现出发育迟缓和癫痫发作。她的癫痫发作不难治，并且易于通过丙戊酸盐控制。她表现出轻度畸形面容与大头畸形，高额头，和间距过宽，也有鸡胸。脑电图显示癫痫放电，很少发生。脑部MRI显示胼胝体短而厚。全外显子组测序检测到SZT 2中的复合杂合双等位基因突变（c.8596dup（p.Tyr2866Leufs*42）和c.2930-17 2930-3delinsCTCGTG），这两个突变都是新的，并且预测为截短的。该病例表明，广泛的表型谱来自SZT 2突变，形成了从癫痫性脑病和严重发育迟缓到无癫痫的轻度智力残疾的连续体。在7/8例癫痫患者（包括先证者）中观察到的特征性厚而短的胼胝体，但在3例非综合征病例中未观察到，这似乎是特异性的，因此可用于指示SZT 2突变的可能性。该特征有可能使SZT 2的丢失成为临床上可辨别的疾病，尽管有广泛的临床谱。2017日本儿童神经病学学会。(C)Elsevier B. V.出版，保留所有权利。
Mutations in SZT2 were first reported in 2013 as a cause of early-onset epileptic encephalopathy. Because only five reports have been published to date, the clinical features associated with SZT2 remain unclear. We herein report an additional patient with biallelic mutations in SZT2. The proband, a four-year-old girl, showed developmental delay and seizures from two years of age. Her seizures were not intractable and readily controlled by valproate. She showed mildly dysmorphic facies with macrocephaly, high forehead, and hypertelorism, and also had pectus carinatum. An EEG showed epileptic discharges which rarely occurred. A brain MRI revealed a short and thick corpus callosum. Whole-exome sequencing detected compound heterozygous biallelic mutations (c.8596dup (p.Tyr2866Leufs*42) and c.2930-17 2930-3delinsCTCGTG) in SZT2, both of which were novel and predicted to be truncating. This case suggested a broad phenotypic spectrum arises from SZT2 mutations, forming a continuum from epileptic encephalopathy and severe developmental delay to mild intellectual disability without epilepsy. The characteristic thick and short corpus callosum observed in 7/8 cases with epilepsy, including the proband, but not in three non-syndromic cases, appears to be specific, and thus useful for indicating the possibility of SZT2 mutations. This feature has the potential to make loss of SZT2 a clinically discernible disorder despite a wide clinical spectrum. 2017 The Japanese Society of Child Neurology. (C) Published by Elsevier B.V. All rights reserved.