Epilepsies in Children with 2q24.3 Deletion/Duplication

Abstract

The chromosome 2q24.3 region appears to be important in childhood epilepsy and contains three genes encoding a sodium channel, which are involved in the disorder (SCN1A, SCN2A, and SCN3A). There have been several reports indicating an association between epilepsy and 2q24.3 deletion or duplication. Epilepsy phenotypes markedly differ between patients with 2q24.3 deletion and those with duplication. The majority of patients with 2q24.3 deletion are characterized by severe epilepsy phenotypes such as Dravet syndrome or Dravet syndrome-like intractable epilepsy, which onsets during infancy. This is particularly applicable to patients with SCN1A deletion. In addition, facial dysmorphism (and other dysmorphic features) is observed in all patients with 2q24.3 deletion-associated epilepsy. SCN1A contributes to epileptogenicity; several other genes involved in the deleted region may also play a role in dysmorphism. In all reported cases, patients with 2q24.3 duplication had neonatal- or infantile-onset epilepsy. Although these patients typically experienced multiple daily seizures, seizures were controlled by the appropriate antiepileptic treatment in the majority of cases. SCN2A and SCN3A were duplicated in all patients and are presumed to contribute to epileptogenicity. Facial or other dysmorphic features were infrequent in patients with 2q24.3 duplication. Array comparative genomic hybridization should be considered in patients with neonatal- or infantile-onset epilepsy, because information obtained using this method is likely to be instructive in diagnosis, prognostication, and treatment regimen decisions.