Abstracts

Rationale: Continuous spike-and-wave during sleep (CSWS) is an electrographic epileptic abnormality that can lead to significant morbidity. The EEG shows near-continuous interictal epileptiform discharges during non-REM sleep. (Specchio et al. (2022). . Epilepsia, 63(6), 1398-1442. ) Patients can have seizures, but often, the main complaints initially are lack of attention and language deterioration. Neurocognitive development is interrupted. Patients will fail to attain new skills or can have a regression, losing skills previously mastered. CSWS can happen in previously normotypical people or in people with previous neurocognitive delay. The causes are unclear, but in some patients, a genetic abnormality has been shown. (Posar, A., & Visconti, P. (2024). Children, 11(2), 169. https://doi.org/10.3390/children11020169) Here we set up to look for genetic causes of CSWS.

Methods: A retrospective chart review was conducted with patients followed at the Adult Genetic Epilepsy Clinic in Toronto, Canada. A literature review was conducted on EE-SWAS and CSWS using PubMed. This included “Genes” and “Genetic” with "SWAS” (Spike-and-wave activation in sleep); “CSWS”, “LKS” (Landau Kleffner Syndrome) and “ESES” (Electrical Status Epilepticus in Sleep).

Results: Out of 699 patients who had genetic testing, seven were identified with a genetic cause for their epilepsy and had CSWS at some point in their lives. Presenting with different degrees of Autism Spectrum Disorder, Intellectual Disability and seizures, we describe two siblings with a deletion involving the SHANK3 gene (Phelan-McDermid Syndrome), one individual with a KMT5B de novo missense variant and another one with an SCN8A missense variant. Finally, polysomnography indicated CSWS in a patient with a CHD2 truncating variant. The last two patients have fallen into the phenotype of Landau Kleffner Syndrome (LKS),
one with a missense known mutation in the GRIN2A gene and the other with a novel mutation as
etiology: a duplication involving the KCNC2 gene.

Conclusions: Here, we share four novel monogenic epilepsies associated with CSWS: SHANK3, KMT5B, SCN8A mutations and KCNC2 (fulfilling criteria for LKS). Current literature indicates a growing diversity in genetic etiologies for this complex framework of conditions. (Lesca et al Epileptic Disorders, 21, S41-S47. https://doi.org/10.1684/epd.2019.1056). As the decision for treatment is challenging and time-sensitive, early recognition of potential conditions related to this finding can prompt increased surveillance and timely intervention if deemed appropriate. The recent broadening from a language-restricted phenotype such as LKS to EE-SWAS is an important advancement. Such understanding will help elaborate on the nature of the cognitive impairment of individuals, which could be everted or at least minimized. This can also lead to further understanding of potential pathways in which this condition leads to pervasive and long-lasting cognitive and behavioural abnormalities.

Funding: No funding was received in support of this abstract.