A longitudinal footprint of genetic epilepsies using automated electronic medical record interpretation

Genet Med. 2020 Dec;22(12):2060-2070. doi: 10.1038/s41436-020-0923-1. Epub 2020 Aug 10.


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.

Keywords: Human Phenotype Ontology; childhood epilepsy; electronic medical records; neurogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Electronic Health Records
  • Epilepsy* / diagnosis
  • Epilepsy* / genetics
  • Humans
  • Intellectual Disability*
  • Phenotype
  • Spasms, Infantile*