Infantile-onset epilepsies encompass a diverse group of epilepsies with onset up to two years of life, and include self-limited epilepsy syndromes, developmental and epileptic encephalopathies (DEEs) and etiology-specific syndromes. DEEs are the most severe, often presenting with early, refractory seizures and developmental delay, and are associated with significant morbidity and mortality.1 In low- and middle-income countries (LMICs), perinatal brain injuries particularly hypoxic-ischemic encephalopathy (HIE) and neonatal hypoglycemic brain injury (NHBI) remain the predominant causes.2 However, genetic etiologies are increasingly recognized, accounting for 10–30 % of cases.3 Delayed treatment initiation, often due to a prolonged diagnostic process, has been linked to poorer outcomes, especially in non-structural etiologies.

Advances in next-generation sequencing (NGS), including whole-exome sequencing (WES) and rapid whole-genome sequencing (rWGS), have transformed the diagnosis of early-onset epilepsies.4,5 These technologies have enabled the identification of hundreds of monogenic epilepsy genes and clarified the broad phenotypic spectrum of genetic epilepsies. Studies now show that 40–60 % of children with epilepsy and comorbidities have pathogenic variants, with an additional 7–10 % carrying chromosomal abnormalities.6, 7, 8 rWGS, in particular, offers high diagnostic yield, reduces unnecessary investigations and hospital costs, and can guide targeted therapies when used early in critically ill infants.9,10

Despite these advances, children in LMICs face persistent barriers to accessing genetic diagnostics, including cost constraints, limited laboratory infrastructure, and a shortage of trained specialists.11 Cultural, ethical, and policy challenges further complicate implementation.12 This review discusses the evolving role of genetic testing in infantile-onset epilepsies in LMICs, outlines current challenges, and explores pragmatic, scalable strategies to improve access and equity in genomic diagnostics for epilepsy care.