CHD2 mutations are a rare cause of generalized epilepsy with myoclonic-atonic seizures.
Chromodomain helicase DNA-binding protein 2 (CHD2) gene mutations have been reported in patients with myoclonic-atonic epilepsy (MAE), as well as in patients with Lennox-Gastaut, Dravet, and Jeavons syndromes and other epileptic encephalopathies featuring generalized epilepsy and intellectual disability. The aim of this study was to assess the impact of CHD2 mutations in a series of patients with MAE. Twenty patients affected by MAE were included in the study. We analyzed antecedents, age at onset, seizure semiology and frequency, EEG, treatment, and neuropsychological outcome. We sequenced the CHD2 gene with Sanger technology. We identified a CHD2 frameshift mutation in one patient (c.4256del19). He was a 17-year-old boy with no familial history for epilepsy and normal development before epilepsy onset. Epilepsy onset was at 3years and 5months: he presented with myoclonic-atonic seizures, head drops, myoclonic jerks, and absences. Interictal EEGs revealed slow background activity associated with generalized epileptiform abnormalities and photoparoxysmal response. His seizures were highly responsive to valproic acid, and an attempt to withdraw it led to seizure recurrence. Neuropsychological evaluation revealed moderate intellectual disability. Chromodomain-helicase-DNA-binding protein 2 is not the major gene associated with MAE. Conversely, CHD2 could be responsible for a proper phenotype characterized by infantile-onset generalized epilepsy, intellectual disability, and photosensitivity, which might overlap with MAE, Lennox-Gastaut, Dravet, and Jeavons syndromes.
Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Marina
M
Trivisano
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy.
Pasquale
P
Striano
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy.
Jacopo
J
Sartorelli
Department of Child and Adolescent Neuropsychiatry, Spedali Civili, Brescia, Italy.
Lucio
L
Giordano
Laboratory of Neurogenetics, Department of Neurosciences, "G. Gaslini" Institute, Genova, Italy.
Monica
M
Traverso
Department of Child and Adolescent Neuropsychiatry, Spedali Civili, Brescia, Italy.
Patrizia
P
Accorsi
Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Simona
S
Cappelletti
Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Dianela Judith
DJ
Claps
Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Federico
F
Vigevano
Laboratory of Neurogenetics, Department of Neurosciences, "G. Gaslini" Institute, Genova, Italy.
Federico
F
Zara
Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: nicola.specchio@opbg.net.
Nicola
N
Specchio
D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
C575189:CHD2 protein, human; D004268:DNA-Binding Proteins
Doose syndrome; Generalized epilepsy; Genetic epilepsy; Myoclonic–atonic epilepsy; Photosensitivity