Department of Paediatrics, University of Pecs, Pécs, Hungary.
Bethesda Children Hospital, Budapest, Hungary.
Epileptic Disord. 2024 Oct;26(5):685-693. doi: 10.1002/epd2.20264. Epub 2024 Jul 17.
PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated.
In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19.
In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam.
The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.
PCDH19 相关性癫痫主要发生于女性，由原钙黏蛋白-19 基因的致病性变异引起。首发癫痫通常与发热相关，平均发病年龄为 15 个月，常呈簇状发作。常伴有孤独症症状、智力障碍和睡眠障碍。
在我们的回顾性多中心研究中，我们对 9 例经基因证实与 PCDH19 相关的癫痫患儿的临床资料进行了回顾。
在年龄 0-18 岁的匈牙利患者人群中，PCDH19 相关性癫痫的患病率（女性为 1/100000 活产）低于国际报道数据（女性为 4-5/100000 活产）。我们的 9 例患者中有 4 例有癫痫阳性家族史（表亲、姐姐和母亲）。我们评估了 3 例患者的脑异常（1 例患者为局灶性皮质发育不良和左前扣带回发育不良，另外 2 例儿童为右侧或左侧海马硬化），另外 3 例患者偶然发现脑部 MRI 有良性改变。9 例患儿中的 7 例首发癫痫呈簇状发作。9 例中有 7 例出现癫痫持续状态。9 例患儿中有 6 例有孤独症症状，仅有 1 例患儿智力正常。9 例患者中有 7 例在联合抗癫痫药物（ASM）治疗下无癫痫发作。最有效的 ASM 是左乙拉西坦、丙戊酸钠和氯巴占。
由于缺乏广泛开展的分子遗传学评估，PCDH19 相关性癫痫的患病率可能被低估。建议对 3 岁前发病的女性癫痫患者进行包括 PCDH19 致病性变异在内的分子遗传学检测。
