Neuropathology findings in KCNQ2 neonatal epileptic encephalopathy

•Mild malformation of cortical development was found in a patient with KCNQ2-epileptic encephalopathy.•The gray-white matter boundary was blurred by excessive heterotopic neurons in the deep white matter.•The presence of neurons in the deep white matter is suggestive of a neuronal migration disorder...

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Published in:Seizure (London, England) England), 2022-07, Vol.99, p.36-39
Main Authors: Legros, Ludovic, Adle-Biassette, Homa, Dozières-Puyravel, Blandine, Khung, Suonavy, Elmaleh-Bergès, Monique, Lesca, Gaëtan, Delanoë, Catherine, Biran, Valérie, Auvin, Stéphane
Format: Article
Language:English
Subjects:
Case report
Cortical development malformation
Epileptic encephalopathy
KCNQ2
Neonatal-onset epilepsy
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Summary:•Mild malformation of cortical development was found in a patient with KCNQ2-epileptic encephalopathy.•The gray-white matter boundary was blurred by excessive heterotopic neurons in the deep white matter.•The presence of neurons in the deep white matter is suggestive of a neuronal migration disorder. KCNQ2-epileptic encephalopathy (EE) is a neonatal epilepsy syndrome characterized by a typical clinical presentation and EEG recording, but without any brain or cortical abnormal development on MRI. Most of the patients have a severe developmental impairment. The epileptogenic mechanisms are thought to be the result of the changes of the M-current density causing a change of brain excitability. Although recent studies allow us to better understand the physiopathology of KCNQ2-EE, the neuropathology of this ion channel dysfunction has only been previously described in a single case report. We report the neuropathology study of a case of KCNQ2-EE with a typical electro-phenotype due to a de novo heterozygous single nucleotide pathogenic variant in the exon 5 of the KCNQ2 gene (NM_172107.2:c.802C>T; p.Leu268Phe). At the macroscopic level, the brain had a normal structure with a normal neocortical gyral pattern. At the histological level, the cortex had a usual six-layer lamination in all lobes but blurred gray-white matter boundaries due to excessive heterotopic neurons in deep white matter were observed. This diffuse mild malformation of cortical development is suggestive of a neuronal migration disorder. In recent years, our understanding of the role of ion channel dysfunctions in early brain development has expanded from the occurrence of EE to brain malformation. Through this rare neuropathological report, we emphasize the role of KCNQ2 channels in the process of cortical development. As for other genetic neonatal onset epilepsies, more reports are needed to further delineate the range of neuropathological abnormalities for KCNQ2-EE.
ISSN:1059-1311
1532-2688
DOI:10.1016/j.seizure.2022.05.008