Kurian Mary, Korff Christian M, Ranza Emmanuelle, Bernasconi Andrea, Lübbig Anja, Nangia Srishti, Ramelli Gian Paolo, Wohlrab Gabriele, Nordli Douglas R, Bast Thomas
Pediatric Neurology Unit, Child and Adolescent Department, University Hospitals, Geneva, Switzerland.
Service of Medical Genetics, University Hospitals, Geneva, Switzerland.
Dev Med Child Neurol. 2018 Jan;60(1):100-105. doi: 10.1111/dmcn.13595. Epub 2017 Oct 24.
In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions.
Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures.
在本病例报告中，我们评估了患有与原钙黏蛋白19（PCDH19）基因变异相关的早发性婴儿癫痫的儿童中皮质畸形的发生率。我们描述了一组药物难治性癫痫女童的临床病程、脑电图、影像学、遗传学和神经病理学特征。所有五名儿童（平均年龄10岁）在婴儿期均有癫痫早发，且以成簇出现的发热敏感性癫痫发作为主。五名患者中有四名存在认知障碍。所有病例均有皮质畸形的影像学证据，其中两名患者经组织学证实。对PCDH19进行的桑格测序和多重连接依赖探针扩增分析显示，四名患者存在致病变异。在一名患者中，阵列比较基因组杂交显示存在一个包含PCDH19的微缺失。我们建议对药物难治性癫痫、婴儿期早发、癫痫成簇发作且对发热敏感的患者进行PCDH19的分子检测和分析。对于存在PCDH19致病变异的患者，应寻找结构性病变。此外，即使存在脑结构性病变，在癫痫手术评估中也应考虑进行PCDH19分析。
局灶性皮质畸形和单基因癫痫综合征可能共存。对于患有原钙黏蛋白19（PCDH19）致病变异且伴有难治性局灶性癫痫发作的患者，应寻找结构性病变。
