Journal article

Genetic convergence of developmental and epileptic encephalopathies and intellectual disability

Gemma L Carvill, Sandra Jansen, Amy Lacroix, Matthew Zemel, Michele Mehaffey, Petra De Vries, Han G Brunner, Ingrid E Scheffer, Bert BA De Vries, Lisenka ELM Vissers, Heather C Mefford



AIM: To determine whether genes that cause developmental and epileptic encephalopathies (DEEs) are more commonly implicated in intellectual disability with epilepsy as a comorbid feature than in intellectual disability only. METHOD: We performed targeted resequencing of 18 genes commonly implicated in DEEs in a cohort of 830 patients with intellectual disability (59% male) and 393 patients with DEEs (52% male). RESULTS: We observed a significant enrichment of pathogenic/likely pathogenic variants in patients with epilepsy and intellectual disability (16 out of 159 in seven genes) compared with intellectual disability only (2 out of 671) (p<1.86×10-10 , odds ratio 37.22, 95% confidence interv..

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University of Melbourne Researchers


Awarded by European Union's Horizon 2020 research and innovation programme

Awarded by National Institutes of Health (NIH)

Funding Acknowledgements

We thank all the patients and families for their participation in this study. The aims of this study contribute to the Solve-RD project (to HB and LELMV) which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 779257. This work was sponsored by National Institutes of Health (NIH) NINDS R00NS089858 (GLC) and NIH/NINDs R01NS069605 to HCM. GLC holds a collaborative research grant with Stoke Therapeutics. IES has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, Chiesi, Encoded Therapeutics, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Sciences, Ovid Therapeutics, Epigenyx, Encoded Therapeutics, and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics, Care Beyond Diagnosis, Epilepsy Consortium, and UCB. She may accrue future revenue on pending patent WO61/010176 (filed 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy [PRRT2] 2011904493 and 2012900190 and PCT/AU2012/001321 (TECH ID 2012-009). The other authors have stated that they had no interests that might be perceived as posing conflict or bias.