Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations
Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations
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DOI：
10.1212/wnl.0000000000003716
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发表时间：
2017-03-14
期刊：
影响因子：
9.9
通讯作者：
Guerrini, Renzo
中科院分区：
文献类型：
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作者：
Cetica, Valentina;Chiari, Sara;Guerrini, Renzo
目的：探讨 SCN1A 突变婴儿的初始临床和突变结果的预后价值。方法：结合性别、年龄/首次癫痫发作时的发烧、癫痫家族史、脑电图和突变类型，我们分析了在癫痫发作后确定的 182 名突变携带者中预测 Dravet 综合征与较轻结局的显着关联的准确性。为了评估所有参数的诊断准确性，我们计算了敏感性、特异性、受试者工作特征 (ROC) 曲线、诊断比值比、阳性和阴性预测值以及组合信息的准确性。我们还在研究中纳入了突变携带者患者健康亲属的人口统计和突变数据。结果：97 人（48.5%）患有 Dravet 综合征，49 人（23.8%）患有全身性/遗传性癫痫伴热性惊厥，30 人（14.8%）患有热性惊厥，6 人（3.5%）患有局灶性癫痫，18 人（8.9%）是健康亲属。关联研究表明，首次癫痫发作年龄和移码突变与 Dravet 综合征相关。 Dravet 综合征的风险在 0 至 6 个月组中为 85%，在 6 至 12 个月组中为 51%，在 12 个月后为 0%。 ROC 分析将第 6 个月内发病确定为进展为 Dravet 综合征的诊断截止点（敏感性 5·83.3%，特异性 5·76.6%）。结论：在具有 SCN1A 突变的个体中，癫痫发作年龄似乎比突变类型更能预测结果。由于结果不仅仅由遗传因素预先决定，因此早期识别和治疗可减轻出生后第一年的长期/反复癫痫发作，也可能限制癫痫性脑病的进展。
Objective: To explore the prognostic value of initial clinical and mutational findings in infants with SCN1A mutations.Methods: Combining sex, age/fever at first seizure, family history of epilepsy, EEG, and mutation type, we analyzed the accuracy of significant associations in predicting Dravet syndrome vs milder outcomes in 182 mutation carriers ascertained after seizure onset. To assess the diagnostic accuracy of all parameters, we calculated sensitivity, specificity, receiver operating characteristic (ROC) curves, diagnostic odds ratios, and positive and negative predictive values and the accuracy of combined information. We also included in the study demographic and mutational data of the healthy relatives of mutation carrier patients.Results: Ninety-seven individuals (48.5%) had Dravet syndrome, 49 (23.8%) had generalized/ genetic epilepsy with febrile seizures plus, 30 (14.8%) had febrile seizures, 6 (3.5%) had focal epilepsy, and 18 (8.9%) were healthy relatives. The association study indicated that age at first seizure and frameshift mutations were associated with Dravet syndrome. The risk of Dravet syndrome was 85% in the 0-to 6-month group, 51% in the 6-to 12-month range, and 0% after the 12th month. ROC analysis identified onset within the sixth month as the diagnostic cutoff for progression to Dravet syndrome (sensitivity 5 83.3%, specificity 5 76.6%).Conclusions: In individuals with SCN1A mutations, age at seizure onset appears to predict outcome better than mutation type. Because outcome is not predetermined by genetic factors only, early recognition and treatment that mitigates prolonged/repeated seizures in the first year of life might also limit the progression to epileptic encephalopathy.