Background

The genetic basis for familial focal epilepsy is poorly understood, with most of the known genetic causes occurring via autosomal dominant inheritance. X-linked familial focal epilepsy has not been previously reported.

Methods

We reviewed our research database for cases of X-linked focal epilepsy.

Results

We identified three boys with X-linked ichthyosis and focal epilepsy, including two maternal cousins. Age of seizure onset ranged from seven to 10 years, and all three patients had seizures that were relatively easily controlled. The epilepsy phenotype in all boys was consistent with self-limited focal epilepsy of childhood, most closely resembling childhood epilepsy with centrotemporal spikes. Brain magnetic resonance imaging was normal in two of the boys, with a third found to have a suspected focal cortical dysplasia. All three boys carried maternally inherited hemizygous Xp22.31 deletions (estimated size 0.9 to 1.66 Mb), affecting four to six genes. Of the affected genes, only STS has clear clinical relevance; deletions, and pathogenic variants in STS cause X-linked ichthyosis, although all patients described had only minor skin findings.

Conclusions

The findings in these patients illustrate that X-linked familial focal epilepsy can occur, although it is a rare entity. Although STS pathogenic variants are likely better categorized as an epilepsy risk factor, variants in this gene may partially explain the male predominance observed in specific epilepsy phenotypes, namely childhood epilepsy with centrotemporal spikes.

中文翻译：

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X连锁相关的Xp22.31缺失家族性癫痫病。

背景

家族性局灶性癫痫的遗传基础知之甚少，大多数已知的遗传原因是通过常染色体显性遗传发生的。X连锁家族性局灶性癫痫尚未见报道。

方法

我们审查了X连锁局灶性癫痫病例的研究数据库。

结果

我们确定了三个男孩，他们患有X型鱼鳞病和局灶性癫痫，包括两个母亲堂兄弟姐妹。癫痫发作的年龄为7至10岁，所有三名患者的癫痫发作都相对容易控制。所有男孩的癫痫表型均与儿童时期的自我局限性局灶性癫痫一致，最类似于儿童癫痫病的中央颞叶尖峰。其中两个男孩的脑磁共振成像正常，其中三分之一发现可疑局灶性皮质发育异常。所有三个男孩均携带母亲遗传性的半合子Xp22.31缺失（估计大小为0.9至1.66 Mb），影响了4至6个基因。在受影响的基因中，只有STS具有明确的临床相关性。STS中的缺失和致病变异 尽管描述的所有患者仅有少量皮肤发现，但可引起X链接鱼鳞病。

结论

这些患者的发现说明，尽管这是一种罕见的疾病，但仍可能发生X连锁的家族性局灶性癫痫。尽管STS病原体变异可能被更好地归类为癫痫危险因素，但该基因的变异可能部分解释了在特定的癫痫表型中观察到的男性优势，即儿童癫痫病具有中央颞叶尖峰。