Epilepsy of Infancy With Migrating Focal Seizures

Abstract

This 3-month-old boy had frequent recurrent events of right-arm stiffening and right head turn suggestive of focal seizures. Continuous electroencephalogram (EEG) showed subclinical focal seizures arising independently from the right occipital and left posterior head regions. These events persisted despite escalating use of lacosamide, levetiracetam, and phenobarbital. Given the patient's age, epilepsy of infancy with migrating focal seizures (EIMFS) was suspected. Early investigation with whole-exome sequencing revealed homozygous pathogenic variants in SLC12A5 (c.986C > A, p.Ala329Asp). Early recognition is vital in this epilepsy syndrome due to the difficulty in treating and subsequent prognosis. Given the expected drug resistance, early or urgent initiation of the ketogenic diet should be considered. The overall prognosis is not favorable, as poor developmental outcomes are expected.

EIMFS is a severe infantile-onset epilepsy syndrome characterized by refractory seizures, developmental delay, and migrating focal discharges [1]. SLC12A5 mutations have been identified as a cause of EIMFS, with nine patients reported to date, but KCNT1 remains responsible for about 50% of cases [2] (Figure 1). SLC12A5 encodes the potassium-chloride cotransporter KCC2, which is crucial for maintaining synaptic inhibition [3]. Mutations in SLC12A5 lead to decreased KCC2 surface expression, impaired chloride extrusion, and reduced protein glycosylation, resulting in neuronal hyperexcitability [3]. EIMFS typically presents before 6 months of age with focal motor seizures that become multifocal and intractable [2]. Treatment options are limited, but the ketogenic diet and potassium bromide have shown potential efficacy [2]. SLC12A5-related EIMFS is inherited in an autosomal recessive manner, with both de novo and inherited mutations reported [4].

Samuel Kamoroff: conceptualization, writing – original draft, writing – review and editing, data curation. Harry Abram: writing – review and editing, data curation, supervision. Fernando Galan: conceptualization, writing – review and editing, data curation, supervision.

The authors declare no conflicts of interest.