Chowdhury Sayoni Roy, Whitney Robyn, RamachandranNair Rajesh, Bijarnia Mahay Sunita, Sharma Suvasini
Department of Paediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India.
Comprehensive Paediatric Epilepsy Program, Division of Neurology, Department of Pediatrics, McMaster Children's Hospital, Hamilton, Ontario, Canada.
Pediatr Neurol. 2024 Aug;157:42-49. doi: 10.1016/j.pediatrneurol.2024.05.008. Epub 2024 May 17.
With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications. Developmental and epileptic encephalopathies, the coexistence of neurodevelopmental comorbidities, early age of epilepsy onset, unexplained drug-refractory epilepsy, and positive family history have demonstrated the highest likelihood of yielding positive genetic test results. Given the diagnostic efficacy across different testing modalities, reducing costs of next-generation sequencing tests, and genetic diversity of epilepsies, exome sequencing or genome sequencing, where feasible and available, have been recommended as the first-tier test. Comprehensive clinical phenotyping at the outset, corroborative evidence from radiology and electrophysiology-based investigations, reverse phenotyping, and periodic reanalysis are some of the valuable strategies when faced with inconclusive test results. In this narrative review, the authors aim to simplify the approach to genetic testing in epilepsy by guiding on the selection of appropriate testing tools in the indicated clinical scenarios, addressing crucial aspects during pre- and post-test counseling sessions, adeptly navigating the traps posed by uncertain or negative genetic variants, and paving the way forward to the emerging testing modalities beyond DNA sequencing.
随着高通量测序和计算方法的出现，基因检测已成为当代临床实践中不可或缺的一部分，尤其是在癫痫领域。基因检测的工具已从传统的染色体微阵列和癫痫基因检测板发展到现代基因组时代的先进测序技术。除了通过精准医学实现治疗益处、优化抗癫痫药物的选择或探索非药物治疗方式的潜力外，基因检测还具有重要的诊断、预后和个人意义。发育性和癫痫性脑病、神经发育合并症的共存、癫痫发病年龄早、原因不明的药物难治性癫痫以及家族史阳性，已被证明产生阳性基因检测结果的可能性最高。鉴于不同检测方式的诊断效果、降低下一代测序检测成本以及癫痫的基因多样性，在可行且可用的情况下，外显子组测序或基因组测序被推荐为一线检测。在面对不确定的检测结果时，最初进行全面的临床表型分析、基于放射学和电生理学检查的佐证证据、反向表型分析以及定期重新分析是一些有价值的策略。在这篇叙述性综述中，作者旨在通过指导在特定临床场景中选择合适的检测工具、解决检测前和检测后咨询过程中的关键问题、巧妙应对不确定或阴性基因变异带来的陷阱以及为超越DNA测序的新兴检测方式铺平道路，简化癫痫基因检测的方法。
