发育性和癫痫性脑病患者基因诊断的预测因素。

Child Neurology Service, Department of Neurology, University of Campinas (UNICAMP), Campinas - São Paulo (SP), Brazil.

Department of Translational Medicine, UNICAMP, Campinas - SP, Brazil.

Epilepsy Behav. 2024 Jun;155:109762. doi: 10.1016/j.yebeh.2024.109762. Epub 2024 Apr 18.

OBJECTIVE

To evaluate the clinical predictors of positive genetic investigation in developmental and epileptic encephalopathies, beyond the influence of Dravet Syndrome.

METHODS

The study included 98 patients diagnosed with developmental and epileptic encephalopathies. The patients underwent Sanger sequencing of SCN1A, Chromosomal Microarray Analysis, and Whole Exome Sequencing. The association of clinical variables with a positive genetic test was investigated using univariate and multivariate analysis.

RESULTS

Genetic diagnosis was identified in 47 (48 %) patients with developmental and epileptic encephalopathies. Beyond Dravet Syndrome influence, first seizure in the context of fever (p < 0.01), seizures precipitated by temperature (p = 0.04), cognitive regression (p = 0.04), hypotonia (p < 0.01), and focal seizures (p = 0.03) increased the chances of a positive genetic investigation. In contrast, atonic seizures (p = 0.01) and generalized discharges on electroencephalogram (p = 0.02) decreased the chances. Dravet Syndrome was positively associated with a genetic developmental and epileptic encephalopathies etiology (p < 0.01), whereas epilepsy with myoclonic-atonic seizures (p = 0.01), developmental and epileptic encephalopathies with spike-wave activation in sleep (p = 0.04), and Lennox-Gastaut syndrome (p = 0.03) were negatively associated. In multivariate analysis, the first seizure in the context of fever (p < 0.01) and hypotonia (p = 0.02) were positively, and atonic seizures (p = 0.01) were negatively and independently associated with a genetic etiology.

CONCLUSION

The predictive variables of genetic investigation in developmental and epileptic encephalopathies are first seizure in the context of fever and hypotonia, whereas atonic seizures decrease the chances of finding a genetic cause for developmental and epileptic encephalopathies. Regarding epileptic syndromes, Dravet Syndrome is highly associated with a positive genetic test, whereas epilepsy with myoclonic-atonic seizures, developmental and epileptic encephalopathies with spike-wave activation in sleep, and Lennox-Gastaut syndrome are rarely associated with a positive genetic investigation.

目的

评估发育性和癫痫性脑病中阳性遗传研究的临床预测因素，超越德雷夫特综合征的影响。

方法

本研究纳入了 98 例诊断为发育性和癫痫性脑病的患者。患者接受 SCN1A 的 Sanger 测序、染色体微阵列分析和全外显子组测序。使用单变量和多变量分析研究临床变量与阳性基因检测结果的关联。

结果

在 98 例发育性和癫痫性脑病患者中，发现 47 例（48%）存在遗传诊断。除德雷夫特综合征影响外，热性惊厥首次发作（p<0.01）、体温诱发的癫痫发作（p=0.04）、认知倒退（p=0.04）、张力减退（p<0.01）和局灶性癫痫发作（p=0.03）增加了阳性遗传研究的可能性。相反，强直发作（p=0.01）和脑电图广泛放电（p=0.02）降低了阳性遗传研究的可能性。德雷夫特综合征与阳性遗传发育性和癫痫性脑病病因呈正相关（p<0.01），而肌阵挛-强直发作的癫痫（p=0.01）、睡眠中棘慢波激活的发育性和癫痫性脑病（p=0.04）和 Lennox-Gastaut 综合征（p=0.03）则呈负相关。多变量分析显示，热性惊厥首次发作（p<0.01）和张力减退（p=0.02）与阳性遗传病因呈正相关，而强直发作（p=0.01）与阳性遗传病因呈负相关。

结论

在发育性和癫痫性脑病中，遗传研究的预测变量是热性惊厥首次发作和张力减退，而强直发作降低了发育性和癫痫性脑病发现遗传原因的可能性。关于癫痫综合征，德雷夫特综合征与阳性基因检测结果高度相关，而肌阵挛-强直发作的癫痫、睡眠中棘慢波激活的发育性和癫痫性脑病以及 Lennox-Gastaut 综合征则很少与阳性基因检测结果相关。