Duplication of the sodium channel gene cluster on 2q24 in children with early onset epilepsy

Abstract

Summary Purpose: Sodium channel gene aberrations are associated with a wide range of seizure disorders, particularly Dravet syndrome. They usually consist of missense or truncating gene mutations or deletions. Duplications involving multiple genes encoding for different sodium channels are not widely known. This article summarizes the clinical, radiologic, and genetic features of patients with 2q24 duplication involving the sodium channel gene cluster. Methods: A systematic review of the literature and report of two cases. Key Findings: Nine individuals with 2q24 duplication involving the sodium channel gene cluster are described (seven female, two male). All presented with severe seizures refractory to anticonvulsant drugs. Seizure onset was in the neonatal period in eight patients with SCN1A‐involvement, in infancy in one patient with SCN2A and SCN3A, but no SCN1A involvement. Seizure activity decreased and eventually stopped at 5–20 months of age. Seizures recurred at the age of 3 years in the patient with SCN2A and SCN3A, but no SCN1A involvement. Eight patients had a poor neurodevelopmental outcome despite seizure freedom. Significance: This article describes a distinct seizure disorder associated with a duplication of the sodium gene cluster on 2q24 described in otherwise healthy neonates and infants with severe, anticonvulsant refractory seizures and poor developmental outcome despite seizure freedom occurring at the age of 5–20 months.

De novo SCN2A splice site mutation in a boy with Autism spectrum disorder

“…Further, the participant’s adaptive and cognitive skills fell in the low range of functioning. No structural brain abnormalities were evident on MRI, which is consistent with past reviews of participants with sodium channel disruptions [ 11 ].…”

Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice

“…Crucial role of SOX5 in neurodevelopment and corticogenesis is confirmed in both mice and drosophila models . SCN3A have been mostly associated with CNV, however, several patients with focal epilepsy have been reported and a single case with a highly compatible phenotype has been presented . Interestingly, upregulated expression of voltage‐gated sodium channel Na v 1.3, encoded by SCN3A , was found in cortical lesions of patients with focal dysplasia type IIb while both patients described by us (case 37 in Table S1) and Jhaveri et al had polymicrogyria.…”

Whole gene duplication of SCN2A and SCN3A is associated with neonatal seizures and a normal intellectual development

“…In most previously published cases, patients showed different degrees of DD and in a majority also ID . However, in the maternally inherited duplication reported by Boutry‐Kryza et al, there was a family history of neonatal epilepsy affecting 10 family members .…”

“…Duplications at 2q24.3 have been described in 10 individuals presenting with early onset epilepsy during the first days of life. In two of these, the duplications were familial with several affected family members .…”