A case of CLCN4-related epilepsy presenting as epilepsy of infancy with migrating focal seizures

CLCN4 pathogenic variants cause X-linked intellectual disability and epilepsy. CLCN4 -related epilepsy presents with a variety of seizures including absence, tonic, and focal seizures, is refractory to treatments, and is complicated by severe global developmental delay. We herein report a case of epilepsy of infancy with migrating focal seizures (EIMFS) in a male infant with CLCN4 variant. The patient was a 3-month-old male with no abnormal perinatal history or family history of epilepsy. Initially, the patient developed convulsive seizures in both upper limbs and the left face, which were refractory to focal epilepsy treatments. Subsequently, a diagnosis of EIMFS was made because the focal sites began to shift from the left hemisphere to the right hemisphere during seizures. The seizures could not be controlled with polytherapy using antiseizure medications, but finally responded to potassium bromide. Whole exome sequencing revealed a novel de novo CLCN4 variant, NM_001830.4:c.854A>G,p.(Tyr285Cys). To date, there have been 24 reported cases of CLCN4 -related epilepsy in the world, with only one case of EIMFS, excluding the present case. Additionally, to the best of our knowledge, there have been no previous reports that included a detailed clinical course of a case of CLCN4 -related epilepsy showing EIMFS. Further studies with accumulation of clinical cases are needed to understand the pathophysiology of CLCN4 -related epilepsy, as well as to establish treatment methods.