Early-life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants
Early-life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants
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DOI：
10.1684/epd.2016.0828
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发表时间：
2016-06-01
影响因子：
2.3
通讯作者：
Millichap, John J.
中科院分区：
文献类型：
--
作者：
Venkatesan, Charu;Angle, Brad;Millichap, John J.
基因检测的进展已经导致越来越多的新基因突变的确定，这些突变是癫痫发作性脑病的基础。最近，一项诱变筛选鉴定出一种新的基因SZT 2，该基因没有已知的蛋白质功能，但与小鼠癫痫发生有关。到目前为止，两份临床报告已经确定了SZT2中具有不同隐性突变和不同临床表型的儿童。一份病例报告描述了癫痫性脑病患者，另一份病例报告指出患者存在认知缺陷，但MRI正常，无癫痫。本病例报告确定了新的突变（复合杂合移码和无义变异）在SZT 2基因与不同的临床和放射学结果相对于以前的报告。我们的病人在2个月大的时候出现了顽固性癫痫。癫痫发作对许多抗癫痫药物无效，患者最终在3岁时通过双丙戊酸钠和拉莫三嗪联合治疗停止癫痫发作。我们的病人有类似的面部畸形（大头畸形，高额头，下斜睑裂）与以前的情况下截断突变。虽然存在发育迟缓和认知缺陷，但我们的病例具有独特的MRI结果，提示以前在其他病例中未报告的偏头痛异常。
Advances in genetic testing have led to the identification of increasing numbers of novel gene mutations that underlie infantile-onset epileptic encephalopathies. Recently, a mutagenesis screen identified a novel gene, SZT2, with no known protein function that has been linked to epileptogenesis in mice. Thus far, two clinical reports have identified children with different recessive mutations in SZT2 and varying clinical phenotypes. One case report described patients with epileptic encephalopathy and the other noted patients with cognitive deficiencies, but normal MRI and no epilepsy. This case report identifies novel mutations (a compound heterozygous frameshift and a nonsense variant) in the SZT2 gene with distinct clinical and radiographic findings relative to those previously reported. Our patient presented with intractable epilepsy at 2 months of age. Seizures were refractory to numerous antiepileptic medications and the patient finally achieved seizure cessation at age 3 years with a combination of divalproex and lamotrigine. Our patient had similar facial dysmorphisms (macrocephaly, high forehead, and down-slanted palpebral fissures) to a previous case with truncating mutation. While developmental delay and cognitive deficiencies were present, our case had unique MRI findings suggesting migrational abnormalities not previously reported in other cases.