PDF(Pubmed)
Abstract：
Epilepsy, characterized by recurrent seizures, impacts 70-80% of patients, leading to cognitive deficits. The intricate relationship between seizure control and cognitive impairment remains complex. Epileptic encephalopathy (EE), an intensified form often rooted in genetic factors, is detectable through next-generation sequencing, aiding in precise diagnoses, family counseling, and potential treatment strategies. We present a case involving two sisters with refractory generalized seizures evolving into dysarthria, dysphagia, ataxia, and cognitive decline. Despite normal physical exams, abnormal electroencephalogram results consistent with epilepsy were noted. Whole Exome Sequencing identified heterozygous variants in the alanyl-tRNA synthetase (AARS) and Calcium Voltage-Gated Channel Subunit Alpha 1 (CACNA1A) genes. The AARS variant (c.C2083T, p.R695*) was maternal, while the CACNA1A variant (c.G7400C, p.R2467P) was paternal. Patients A and B exhibited a unique blend of neurological and psychiatric conditions, distinct from common disorders that begin adolescence, like Juvenile Myoclonic Epilepsy. Whole Exome Sequencing uncovered an AARS gene and CACNA1A gene, linked to various autosomal dominant phenotypes. Presence in both parents, coupled with familial reports of migraines and seizures, provides insight into accelerated symptom progression. This study underscores the importance of genetic testing in decoding complex phenotypes and emphasizes the value of documenting family history for anticipating related symptoms and future health risks.
摘要：
癫痫,以反复发作为特征，影响70-80%的患者，导致认知缺陷。癫痫发作控制和认知障碍之间的复杂关系仍然很复杂。癫痫脑病(EE),一种通常植根于遗传因素的强化形式，可以通过下一代测序检测到，帮助精确诊断，家庭咨询,和潜在的治疗策略。我们介绍了一个涉及两个姐妹的难治性全身性癫痫发作演变成构音障碍的病例，吞咽困难,共济失调,和认知能力下降。尽管体检正常,脑电图异常结果与癫痫一致。全外显子组测序鉴定了丙氨酰-tRNA合成酶(AARS)和钙电压门控通道亚基α1(CACNA1A)基因中的杂合变体。AARS变体（c。C2083T,p.R695*)是母体，而CACNA1A变体(c.G7400C,p.R2467P)为父系。患者A和B表现出独特的神经和精神疾病混合，不同于青春期开始的常见疾病，就像青少年肌阵挛性癫痫.全外显子组测序发现了AARS基因和CACNA1A基因，与各种常染色体显性表型相关。父母双方的存在，再加上偏头痛和癫痫发作的家族报告，提供对加速症状进展的洞察。这项研究强调了基因检测在解码复杂表型中的重要性，并强调了记录家族史对预测相关症状和未来健康风险的价值。
