KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
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DOI：
10.1002/ana.22644
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发表时间：
2012-01-01
影响因子：
11.2
通讯作者：
de Jonghe, Peter
中科院分区：
文献类型：
--
作者：
Weckhuysen, Sarah;Mandelstam, Simone;de Jonghe, Peter
目的：已知 KCNQ2 和 KCNQ3 突变导致良性家族性新生儿癫痫发作 (BFNS)。有一些关于 KCNQ2 突变患者具有更严重结果的报告，但尚未建立明确的关系。在这项研究中，我们调查了 KCNQ2/3 突变是否是早发性癫痫性脑病的常见原因，以及是否存在可识别的表型。方法：我们分析了 80 名患有不明原因新生儿或早期婴儿癫痫发作以及相关精神运动迟缓的 KCNQ2 和 KCNQ3 突变患者。详细审查了临床和影像数据。结果：我们在 8 名患者中发现了 7 种不同的杂合 KCNQ2 突变（8/ 80；10%）； 6个突变从头出现。一位具有较温和表型的亲本因突变而呈嵌合体。未发现 KCNQ3 突变。 8 名患者在出生后第一周内出现顽固性癫痫发作，并伴有明显的强直成分。癫痫发作通常在 3 岁时得到缓解，但儿童患有严重的或不太严重的智力障碍和运动障碍。发病时脑电图（EEG）显示爆发抑制模式或多灶性癫痫样活动。早期大脑磁共振成像（MRI）显示基底神经节和丘脑出现特征性高信号，但随后消失。解释：KCNQ2 突变存在于相当大比例的新生儿癫痫性脑病患者中，且具有潜在可识别的电临床和放射学表型。这表明 KCNQ2 筛查应纳入不明原因难治性新生儿癫痫发作的诊断检查中。安神经学 2012； 71：15-25
Objective: KCNQ2 and KCNQ3 mutations are known to be responsible for benign familial neonatal seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether a recognizable phenotype exists. Methods: We analyzed 80 patients with unexplained neonatal or early-infantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail. Results: We found 7 different heterozygous KCNQ2 mutations in 8 patients (8/ 80; 10%); 6 mutations arose de novo. One parent with a milder phenotype was mosaic for the mutation. No KCNQ3 mutations were found. The 8 patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had profound, or less frequently severe, intellectual disability with motor impairment. Electroencephalography (EEG) at onset showed a burst-suppression pattern or multifocal epileptiform activity. Early magnetic resonance imaging (MRI) of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. Interpretation: KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a potentially recognizable electroclinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin. ANN NEUROL 2012; 71: 15-25