Purpose

Childhood epilepsies have a strong genetic contribution, but the disease trajectory for many genetic etiologies remains unknown. Electronic medical record (EMR) data potentially allow for the analysis of longitudinal clinical information but this has not yet been explored.

Methods

We analyzed provider-entered neurological diagnoses made at 62,104 patient encounters from 658 individuals with known or presumed genetic epilepsies. To harmonize clinical terminology, we mapped clinical descriptors to Human Phenotype Ontology (HPO) terms and inferred higher-level phenotypic concepts. We then binned the resulting 286,085 HPO terms to 100 3-month time intervals and assessed gene–phenotype associations at each interval.

Results

We analyzed a median follow-up of 6.9 years per patient and a cumulative 3251 patient years. Correcting for multiple testing, we identified significant associations between “Status epilepticus” with SCN1A at 1.0 years, “Severe intellectual disability” with PURA at 9.75 years, and “Infantile spasms” and “Epileptic spasms” with STXBP1 at 0.5 years. The identified associations reflect known clinical features of these conditions, and manual chart review excluded provider bias.

Conclusion

Some aspects of the longitudinal disease histories can be reconstructed through EMR data and reveal significant gene–phenotype associations, even within closely related conditions. Gene-specific EMR footprints may enable outcome studies and clinical decision support.

中文翻译：

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使用自动电子病历解释的遗传性癫痫纵向足迹。

目的

儿童癫痫具有很强的遗传贡献，但许多遗传病因的疾病轨迹仍然未知。电子病历 (EMR) 数据可能允许分析纵向临床信息，但这尚未得到探索。

方法

我们分析了 658 名已知或推测为遗传性癫痫患者的 62,104 名患者就诊时提供者输入的神经系统诊断。为了协调临床术语，我们将临床描述符映射到人类表型本体 (HPO) 术语并推断出更高级别的表型概念。然后，我们将得到的 286,085 个 HPO 术语分类为 100 个 3 个月的时间间隔，并在每个间隔评估基因-表型关联。

结果

我们分析了每位患者的中位随访时间为 6.9 年，累计 3251 患者年。校正多项测试后，我们发现“癫痫持续状态”与SCN1A在 1.0 年、“严重智力障碍”与PURA在 9.75 年以及“婴儿痉挛”和“癫痫痉挛”与STXBP1在 0.5 年之间存在显着关联。确定的关联反映了这些疾病的已知临床特征，并且手动图表审查排除了提供者的偏见。

结论

纵向疾病史的某些方面可以通过 EMR 数据重建，并揭示显着的基因-表型关联，即使在密切相关的条件下也是如此。基因特异性 EMR 足迹可以实现结果研究和临床决策支持。