Myoclonic Epilepsy: Case Report of a Mild Phenotype in a Pediatric Patient Expanding Clinical Spectrum of KCNA2 Pathogenic Variants

Abstract

We report on the rare case of a male toddler presenting with myoclonic epilepsy characterized by daily episodes of upward movements of the eyebrows, and myoclonic jerks of both head and upper limbs. In addition, the child showed speech delay, tremors, and lack of motor coordination. Next Generation Sequencing analysis (NGS) performed in trio revealed in the proband the c.889C>T de novo missense variant in the KCNA2 gene in heterozygous state. This is the first case of myoclonic epilepsy in a toddler due to a c.889C>T KCNA2 missense variant. The patient was treated with valproic acid and ethosuximide with a good clinical response. At 6 years old, follow-up revealed that the proband was seizure-free with tremors and clumsiness in movements. According to the literature, this case supports the correlation between myoclonic epilepsy and KCNA2 alterations. This evidence suggests that performing genomic testing including the KCNA2 gene in preschool patients affected by myoclonic epilepsy, especially when associated with delayed neurodevelopment. Our goal is to expand the phenotypical spectrum of this rare condition and adding clinical features following a genotype-first approach.

Potassium channel‐related epilepsy: Pathogenesis and clinical features

“…31 Seizures of this phenotype have also been controlled using valproate sodium (VPA) in combination with ethosuximide. 32 In addition to epilepsy, KCNA2 variants have been identified in other diseases in recent years. Canafoglia et al reported one male patient carrying a KCNA2 GOF variant who presented with only progressive myoclonus epilepsy (PME).…”

“… 31 Seizures of this phenotype have also been controlled using valproate sodium (VPA) in combination with ethosuximide. 32 …”

“…ACZ has been found to be effective in controlling seizures of this phenotype 31 . Seizures of this phenotype have also been controlled using valproate sodium (VPA) in combination with ethosuximide 32 …”