Xu Yan, Wu Bing-Bing, Wang Hui-Jun, Zhou Shui-Zhen, Cheng Guo-Qiang, Zhou Yuan-Feng
Department of Neurology, Children's Hospital of Fudan University, Shanghai, China.
The Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defects, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.
Transl Pediatr. 2020 Oct;9(5):707-712. doi: 10.21037/tp-20-110.
The gene encodes mitochondrial arginine-tRNA synthetase. Patients with variants of the gene have pontocerebellar hypoplasia type 6 (PCH6), which is characterized by early onset seizures, progressive microcephaly, and developmental delay. PCH6 is a rare mitochondrial encephalopathy. To the best of our knowledge, the onset seizure type which the ictal video-electroencephalogram (VEEG) was compatible with early myoclonic encephalopathy (EME) has not been reported. Here we reported a term female neonate with EME caused by heterozygous variants of the gene [NM_020320: exon10: c.773G>A (p. R258H) Maternal, NM_020320: exon4: c.282_285delAGAG Paternal]. Groan was the first symptom manifested, followed by metabolic disorders, and early marked cerebral atrophy. Metabolic disorders were corrected after feeding with extensively hydrolyzed protein formula. Seizures started at the 19th day of life. Interictal VEEG showed a suppression-burst (SB) pattern and ictal VEEG revealed myoclonic seizures that were compatible with early myoclonic encephalopathy (EME). She had frequent myoclonic seizures resistant to multi-antiepileptic drugs including phenobarbital, levetiracetam and oxcarbazepine, and soon developed into convulsive status epilepticus. At 7 months of age, she had severe developmental delay, and developed infantile spasms. Our case report expands the phenotypic spectrum of the PCH6, meanwhile, should be considered be a causative gene in patients with EME.
该基因编码线粒体精氨酸 - 转运RNA合成酶。该基因变异的患者患有6型脑桥小脑发育不全（PCH6），其特征为早发性癫痫发作、进行性小头畸形和发育迟缓。PCH6是一种罕见的线粒体脑病。据我们所知，发作期视频脑电图（VEEG）与早期肌阵挛性脑病（EME）相符的发作癫痫类型尚未见报道。在此，我们报告了一名足月女新生儿，其患有由该基因杂合变异[NM_020320：外显子10：c.773G>A（p.R258H），母系；NM_020320：外显子4：c.282_285delAGAG，父系]引起的EME。呻吟是最初出现的症状，随后出现代谢紊乱和早期明显的脑萎缩。采用深度水解蛋白配方奶喂养后代谢紊乱得到纠正。癫痫发作始于出生后第19天。发作间期VEEG显示抑制 - 爆发（SB）模式，发作期VEEG显示与早期肌阵挛性脑病（EME）相符的肌阵挛发作。她频繁出现肌阵挛发作，对包括苯巴比妥、左乙拉西坦和奥卡西平在内的多种抗癫痫药物耐药，很快发展为惊厥性癫痫持续状态。7个月大时，她出现严重发育迟缓，并出现婴儿痉挛症。我们的病例报告扩展了PCH6的表型谱，同时，对于EME患者应考虑该基因是致病基因。
