The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile-onset epilepsy was noted in 81% of these families (61/74). Fifty-five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single-nucleotide variants/small insertion-deletions, 1 (2%) copy-number variant, and 1 (2%) triplet-repeat expansion in 53 epilepsy-associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty-one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.

中文翻译：

---

142 个印度家庭中小儿癫痫的遗传和表型状况：咨询和治疗意义

基因组技术的应用揭示了癫痫疾病的复杂遗传图谱，深入了解其潜在的疾病机制，帮助精准医疗，并提供知情的遗传咨询。我们在此介绍 142 个患有或不患有合并症的癫痫患者的印度家庭的表型和基因型见解。根据电临床结果，采用 ILAE 工作组 (2022) 最新分类建议的家庭中有 44% (63/142) 可以做出癫痫综合征诊断。其中，95% (60/63) 的家庭表现出发育性癫痫性脑病或进行性神经功能恶化的综合征。142 个家庭中的 74 个 (52%) 获得了明确的分子诊断。其中 81% 的家庭患有婴儿期癫痫 (61/74)。在 74 个家系中鉴定出 55 种单基因疾病、4 种染色体疾病和 1 种印记疾病。遗传变异包括导致单基因疾病的 53 个癫痫相关基因中的 65 个（96%）单核苷酸变异/小插入缺失、1 个（2%）拷贝数变异和 1 个（2%）三联体重复扩增。其中，35 个 (52%) 变体是新颖的。51% (38/74) 的确诊家庭注意到了治疗意义。66 个患有单基因疾病的家庭中有 41 个表现出常染色体隐性遗传和遗传性常染色体显性遗传疾病，且复发风险很高。