New Variant of KDM5C in Sibling Brothers Presents with Severe Epilepsy
Abstract number :
3.409
Submission category :
18. Case Studies
Year :
2023
Submission ID :
689
Source :
www.aesnet.org
Presentation date :
12/4/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Rumi Dasgupta, MSc – University of Calgary
Toni-Lee Sterley, PhD, Medical Student – University of Calgary; Minette Manalo, MD – University of Calgary; Micheil Innes, MD – University of Calgary; Julia Jacobs-LeVan, MD – University of Calgary
Rationale:
Mutation in the KDM5C gene result in X-linked neurodevelopmental disorders. There are several variants and their clinical picture reported for KDM5C. Information about the phenotype of epilepsy and EEG changes with this developmental disorder are limited. Here we report a new pathogenic variant discovered in siblings causing refractory epilepsy and encephalopathic EEG changes.
Methods:
We performed a review of medical charts, seizure diaries, and EEG reports for both affected siblings. This was followed by a systematic review of the literature on mutations in the KDM5C gene for reported seizure types, epilepsy severity, and EEG changes.
Results:
Both affected brothers had a new variant, c.3728T >C (p.Leu1243Pro), in the KDM5C gene, which is classified as a missense variant. The EpiSign test indicated an abnormal targeted methylation analysis, consistent with Claes-Jensen syndrome. Both brothers originally presented with intellectual disability, severe language impairment, and seizures. The disease progression and increased language disturbance at seizure onset was seen in both brothers, with the younger brother showing an EEG consistent of DEE-SWAS. As a result, developmental regression was first interpreted as part of an epileptic encephalopathy. Review of literature suggests epilepsy in 53% and EEG abnormalities in 0.7 – 2.8 % of cases with KDM5C- linked developmental disorder. Cases of refractory epilepsy and DEE-SWAS are currently not reported.
Conclusions:
KDM5C mutations are one of the most common causes of X-linked intellectual disability. Our study reports two male siblings with a new pathogenic variant. It appears to be associated with more severe epilepsy and EEG abnormalities that can mimic epileptic encephalopathy. Current description of seizure types and EEG changes in KDM5C-linked disease are scarce and superficial. A more detailed analysis can help to better understand the link between epilepsy and X-linked disability.
Funding:
Alberta Children’s Epilepsy Program is supported by Alberta Children’s Epilepsy Foundations
Case Studies