CHD2 (chromodomain helicase DNA binding protein 2)-related disorders present a broad phenotypic range from mild intellectual disability to childhood epileptic encephalopathies with multiple seizure semiologies. The majority of cases report de novo variants, however this case represents the first described paternally-inherited CHD2-related epilepsy from a clinically affected father with a milder phenotype compared to the proband.

We report a five-year-old girl who first presented at age two-and-a-half years with generalized tonic-clonic seizures with an EEG demonstrating generalized spike and slow wave discharges. Over the next year, she developed atonic seizures, absence seizures, and myoclonic seizures meeting the criteria for Lennox-Gastaut syndrome and was refractory to treatment with multiple anti-epileptic drugs (AED). Due to financial constraints, all therapy was discontinued by her parents. Following AED discontinuation, the patient unexpectedly developed spontaneous clinical resolution of seizures with improvement in speech, behavior, and cognitive abilities.

The present study is novel in that it reports the first known case of likely CHD2-related epilepsy that has shown spontaneous clinical resolution of a previously medically refractory Lennox-Gastaut epileptic encephalopathy. One limitation to the study is the absence of a follow-up EEG, which limits our ability to conclude that sub-clinical seizures have resolved. As phenotypic characterization of a CHD2-related epilepsy syndrome continues to develop, this report provides evidence regarding disease heritability and penetrance and supplies important prognostic considerations that may provide parental guidance and inform treatment decisions.