AUTHOR=Dalen Meurs-van der Schoor Charlotte , van Weissenbruch Mirjam , van Kempen Marjan , Bugiani Marianna , Aronica Eleonora , Ronner Hanneke , Vermeulen R. Jeroen 

TITLE=Severe Neonatal Epileptic Encephalopathy and KCNQ2 Mutation: Neuropathological Substrate?

JOURNAL=Frontiers in Pediatrics

VOLUME=2

YEAR=2014

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2014.00136

DOI=10.3389/fped.2014.00136

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes.</p><p><bold>Methods:</bold> We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus.</p><p><bold>Results:</bold> This case report provides electroencephalogram (EEG), MRI, genetic analysis, and neuropathological data. Genetic analysis revealed a <italic>de novo</italic> heterozygous missense mutation in the <italic>KCNQ2</italic> gene, which encodes a subunit of a voltage-gated potassium channel<italic>. KCNQ2</italic> gene mutation is associated with intractable neonatal seizures. EEG, MRI, data as well as mutation analysis have been described in other <italic>KCNQ2</italic> cases. Post-mortem neuropathological investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a <italic>KCNQ2</italic> mutation and the cortical abnormalities.</p><p><bold>Conclusion:</bold><italic>KCNQ2</italic> mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the <italic>KCNQ2</italic> mutation or are secondary to the refractory seizures.</p>