Abstract：
OBJECTIVE: Studies on the genetic yield of developmental and epileptic encephalopathy and Epileptic encephalopathies using next-generation sequencing techniques are sparse from the Indian subcontinent. Hence, the study was conducted to assess the yield of genetic testing and the proportion of children where a positive genetic yield influenced treatment decisions.
METHODS: In this retrospective observational study, electronic medical records of children (0-12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants.
RESULTS: A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p = .07). Yield was not statistically significant across different age groups (p = .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p = .04). After genetic diagnosis and drug optimization, drug-refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control.
CONCLUSIONS: A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next-generation sequencing-based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.
METHODS: In this retrospective observational study, electronic medical records of children (0-12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants.
RESULTS: A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p = .07). Yield was not statistically significant across different age groups (p = .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p = .04). After genetic diagnosis and drug optimization, drug-refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control.
CONCLUSIONS: A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next-generation sequencing-based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.
摘要：
目的：使用下一代测序技术对发育性和癫痫性脑病和癫痫性脑病的遗传产量的研究在印度次大陆很少。因此，进行这项研究是为了评估基因检测的产量以及基因产量阳性影响治疗决定的儿童比例。
方法：在这项回顾性观察研究中，使用全外显子组测序进行基因检测的疑似遗传性癫痫儿童（0-12岁）的电子病历，检索了集中的外显子组测序和癫痫基因面板。基于致病性和可能的致病性变体的检测来确定遗传产量。
结果：共有100例癫痫患者接受了基因检测。获得53.8%(42/78)的产率。在18例（42.8％）病例中发现了致病性变异，在24例（57.1％）病例中发现了可能的致病性变异。通过全外显子组测序，产量分别为66.6%，集中外显子组测序和40%通过癫痫基因面板(p=.07)。不同年龄组的产量无统计学意义(p=2)。然而，发现在不同的癫痫综合征中存在显着差异，婴儿期癫痫发作的最大产量为2（100％），其次是发育性和癫痫性脑病，未指明14例（77.7%），14人中的德拉韦综合征（60.8%），早期婴儿发育性和癫痫性脑病3（60％），婴儿癫痫性痉挛综合征5例（35.7%），和其他癫痫性脑病4例（30.7%）（p=.04）。经过基因诊断和药物优化，药物难治性比例从73.8%降至45.3%。大约一半的病例实现了癫痫发作控制。
结论：使用基于下一代测序的技术，无论组或外显子组或年龄组的选择如何，都获得了53.8%的合理高产率。然而，某些癫痫综合征的产量较高，而婴儿癫痫痉挛综合征的产量较低。特定的基因诊断促进了量身定制的治疗，导致28.6％的癫痫发作自由和54.7％的癫痫发作明显减少。
方法：在这项回顾性观察研究中，使用全外显子组测序进行基因检测的疑似遗传性癫痫儿童（0-12岁）的电子病历，检索了集中的外显子组测序和癫痫基因面板。基于致病性和可能的致病性变体的检测来确定遗传产量。
结果：共有100例癫痫患者接受了基因检测。获得53.8%(42/78)的产率。在18例（42.8％）病例中发现了致病性变异，在24例（57.1％）病例中发现了可能的致病性变异。通过全外显子组测序，产量分别为66.6%，集中外显子组测序和40%通过癫痫基因面板(p=.07)。不同年龄组的产量无统计学意义(p=2)。然而，发现在不同的癫痫综合征中存在显着差异，婴儿期癫痫发作的最大产量为2（100％），其次是发育性和癫痫性脑病，未指明14例（77.7%），14人中的德拉韦综合征（60.8%），早期婴儿发育性和癫痫性脑病3（60％），婴儿癫痫性痉挛综合征5例（35.7%），和其他癫痫性脑病4例（30.7%）（p=.04）。经过基因诊断和药物优化，药物难治性比例从73.8%降至45.3%。大约一半的病例实现了癫痫发作控制。
结论：使用基于下一代测序的技术，无论组或外显子组或年龄组的选择如何，都获得了53.8%的合理高产率。然而，某些癫痫综合征的产量较高，而婴儿癫痫痉挛综合征的产量较低。特定的基因诊断促进了量身定制的治疗，导致28.6％的癫痫发作自由和54.7％的癫痫发作明显减少。
