The genetic landscape of developmental and epileptic encephalopathy with spike-and-wave activation in sleep.

Epileptic Encephalopathy / Developmental Epileptic Encephalopathy with spike-and-wave activation in sleep (EE/DEE-SWAS) is defined as an epilepsy syndrome characterized by neurodevelopmental regression temporally related to the emergence of significant activation of spike-wave discharges in EEG during sleep. The availability of genetic testing has made it evident that monogenic and chromosomal abnormalities play an aetiological role in the development of EE/DEE-SWAS. We sought to review the literature to better understand the genetic landscape of EE/DEE-SWAS. In this systematic review, we reviewed cases of EE/DEE-SWAS associated with a genetic aetiology, collecting information related to the underlying aetiology, onset, management, and EEG patterns. One hundred and seventy-two cases of EE/DEE-SWAS were identified. Genetic causes of note included pathogenic variants in GRIN2A, ZEB2, CNKSR2 and chromosome 17q21.31 deletions, each of which demonstrated unique clinical characteristics, EEG patterns, and age of onset. Factors identified to raise suspicion of a potential genetic aetiology included the presentation of DEE-SWAS and onset of SWAS under the age of five years. Treatment of EE/DEE-SWAS due to genetic causes was diverse, including a combination of anti-seizure medications, steroids, and other clinical strategies, with no clear consensus on a preferred or superior treatment. Data collected was significantly heterogeneous, with a lack of consistent use of neuropsychology testing, EEG patterns, or use of established clinical definitions. Uniformity concerning the new definition of EE/DEE-SWAS, guidelines for management and more frequent genetic screening will be needed to guide best practices for the treatment of patients with EE/DEE-SWAS.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest Rajesh RamachandranNair received a research grant from the Ontario Brain Institute and served as a paid consultant to UCB Canada Inc. and Sunovion Pharmaceuticals Canada Inc. The remaining authors have no conflicts of interest.