Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES)

Claudia M. Bonardi*, Cyril Mignot, Jose M. Serratosa, Beatriz G. Giraldez, Raffaella Moretti, Gabrielle Rudolf, Chiara Reale, Pia M. Gellert, Katrine M. Johannesen, Gaetan Lesca, Carlo A. Tassinari, Elena Gardella, Rikke S. Møller, Guido Rubboli

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Objective: To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. Methods: Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES. Results: Neurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2–6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60–96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood. Conclusions: Novel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia. Significance: Our findings expand the phenotypic spectrum of CNKSR2-related ESES.

Original languageEnglish
JournalClinical Neurophysiology
Issue number5
Pages (from-to)1030-1039
Publication statusPublished - May 2020


  • CNKSR2
  • Encephalopathy
  • ESES
  • Speech/oro-motor dyspraxia
  • Spike-wave-index (SWI)
  • X-linked intellectual disabilities


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