CNKSR2-Related Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep: A Report of Two Additional Cases and Review of the Literature

CNKSR2 variants have been associated with X linked intellectual disability and epilepsy including developmental and epileptic encephalopathy with spike wave activation in sleep (D/EE SWAS) in males. We aimed to describe a sibling pair with a novel pathogenic variant in CNKSR2 with D/EE SWAS and revi...

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Bibliographic Details
Published in:Neurology India 2024-01, Vol.72 (1), p.129-137
Main Authors: Whitney, Robyn, Go, Cristina, Abushama, Ahmed, Jain, Puneet
Format: Article
Language:English
Subjects:
Care and treatment
Convulsions & seizures
Diagnosis
Encephalopathy
Epilepsy
Genetic counseling
Health aspects
Literature reviews
Sleep
Surveillance
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Summary:CNKSR2 variants have been associated with X linked intellectual disability and epilepsy including developmental and epileptic encephalopathy with spike wave activation in sleep (D/EE SWAS) in males. We aimed to describe a sibling pair with a novel pathogenic variant in CNKSR2 with D/EE SWAS and review published cases of D/EE SWAS. A retrospective chart review and a comprehensive review of the literature were conducted. Two brothers with a novel pathogenic variant in the CNKSR2 gene (c. 114delG, p.Ile39SerfsX14) were identified. The epilepsy phenotype was similar to previous cases and was characterized by early onset seizures, nocturnal seizures (focal motor with/without impaired awareness), global developmental delay and language impairment, frontal central temporal predominant epileptiform discharges with a spike wave index >95%, and treatment resistance. However, phenotypic variability was observed and the younger brother had milder neuro developmental impairment, and the diagnosis of D/EE SWAS was made by surveillance electro encephalogram (EEG). Literature search yielded 23 cases, and their clinical/neuro physiological features are discussed. To conclude, CNKSR2 related D/EE SWAS may be early onset and occur before the age of 5 years in some. Early surveillance EEG may aid in diagnosis. Phenotypic variability was observed in our cases as well as sibling pairs in the literature, which may impact genetic counseling.
ISSN:0028-3886
1998-4022
DOI:10.4103/ni.ni_1191_21