ATP1A3-related early childhood onset developmental and epileptic encephalopathy responding to corpus callosotomy: A...

VariousATP1A3variant-related diseases have been reported, including alternating hemiplegia of childhood; rapid-onset dystonia-parkinsonism; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. Moreover, a few cases of developmental and epileptic encephalopathy (DEE) with none of these symptoms have been reported. Here, we present a case of DEE with early childhood onset caused by anATP1A3variant that was effectively treated using corpus callosotomy (CC).

At the age of 3 years, the patient developed epileptic spasms, complicated by generalized and focal aware tonic seizures. Based on the seizure type and electroencephalographic findings showing a generalized spike and waves as well as interictal left frontal-dominant spikes, combined generalized and focal epilepsy was diagnosed. Whole-exome sequencing revealed a de novo missense variant inATP1A3(c.2888G > A, p.Gly963Asp), which was classified as likely pathogenic. At the age of 5 years, CC for generalized tonic seizures resulted in seizure-freedom using two anti-seizure medications. Subsequently, the patient achieved better verbal development.

Early childhood onset DEE has not been reported in patients with ATP1A3 variants. Moreover, CC was extremely effective in our case. Although more research is needed to determine the etiology of epilepsy caused by theATP1A3 variant, the clinical course of DEE caused by the ATP1A3 variant is diverse and its prognosis may be improved in early childhood onset cases using aggressive control of epilepsy, such as CC.