摘要目的:总结 NPRL2变异相关癫痫的临床表型、基因型及治疗转归。 方法:病例总结。回顾性总结北京大学人民医院儿科2013年10月1日至2023年10月31日收治的 NPRL2变异患儿的病例资料，并对既往报道的病例进行文献复习。 结果:共收集6例 NPRL2变异相关癫痫患儿，既往文献报道37例。患者起病中位年龄24个月(3 d至18岁)，其中婴儿期起病15例。41例患者诊断癫痫，局灶性发作73.1%(30/41)，其中额叶起始癫痫发作34.1%(14/41)，癫痫性痉挛17.1%(7/41)。已知头颅影像学结果的患者中，58.6%(17/29)存在皮质发育畸形。 NPRL2变异中，11例为无义变异，10例为剪切位点变异，7例为移码变异，1例为大片段缺失，14例为错义变异；39例为致病或可能致病性，4例致病意义不明。已知转归的27例中，11例(40.7%)单药或两药控制无发作，16例(59.2%)为药物难治性癫痫(其中1例应用3种抗癫痫发作药物后发作控制，7例经手术治疗达到无发作)。大部分患者智力运动发育不同程度落后。 结论:NPRL2变异起病年龄变化大，表现为局灶性发作、痉挛发作，发作频繁，约一半患者为药物难治性癫痫，半数存在皮质发育畸形，药物难治性癫痫且头颅影像学异常者可考虑癫痫外科手术。

abstractsObjective:To summarize the clinical phenotypes, genotypes, and treatment outcomes of NPRL2-related epilepsy. Methods:This was a case summary.Clinical data of patients with NRPL2 variants admitted to the Department of Pediatrics, Peking University People′s Hospital between October 1, 2013 and October 31, 2023 were retrospectively analyzed.Previous reports of patients with the same disease were reviewed. Results:Six cases of NPRL2-related epilepsy were collected, and 37 cases were reported in the previous literatures.The age of onset ranged from 3 days to 18 years with the median age of 24 months.There were 15 patients with onset in infancy.Among the 41 patients diagnosed with epilepsy, 73.1% (30/41) had focal seizures, 34.1% (14/41) had frontal lobe epilepsy, and 17.1% (7/41) had epileptic spasms.Among the patients with known cranial imaging, 58.6% (17/29) had cortical malformations. NPRL2 variants involved 11 nonsense mutations, 10 splice site mutations, 7 frameshift mutations, 1 large fragment deletion, and 14 missense mutations; among them, 39 mutations were pathogenic or likely pathogenic, while the rest 4 mutations had unclear pathogenicity.Among the 27 patients with known outcomes, 11 (40.7%) had no seizures after administration of 1 or 2 types of drugs, and 16 (59.2%) had drug-resistant epilepsy.Among the 16 patients, 1 had no seizures after treatment with 3 types of anti seizure medications, and 7 had no seizures after surgery.Most patients had varying degrees of delay in intellectual and motor development. Conclusions:Patients with NPRL2 variants usually present with frequent focal seizures and epileptic spasms, and the age of onset varies greatly.About half of the patients have drug-resistant epilepsy, half of whom have cortical malformations.For those with drug-resistant epilepsy and abnormal cranial imaging, surgery may be considered.