Recurrent IRF2BPL c.2152del Variant in NEDAMSS : A Case Report and Comparative Analysis

We describe a male child with a de novo IRF2BPL c.2152del (p.Cys718Alafs*49) frameshift variant presenting with early-onset NEDAMSS and West Syndrome, and compare this phenotype with two previously reported cases carrying the same variant. This is the third report of this specific variant and the first to include a comparative phenotypic analysis, highlighting a potentially consistent and severe clinical pattern. The patient was identified through clinical evaluation and exome sequencing (ES) after presenting with early developmental regression and drug-resistant epilepsy. A literature search identified two additional cases with the same variant and a comparative analysis was conducted. The patient showed neonatal axial hypotonia, early neurodevelopmental regression and epilepsy evolving into West syndrome. Brain MRI revealed corpus callosum thinning and hippocampal malrotation. EEG evolved from burst-attenuation to hypsarrhythmia. ES identified a de novo c.2152del IRF2BPL variant. In comparison, all three cases shared profound hypotonia, severe neurodevelopmental impairment, and early-onset epileptic encephalopathy. These findings support the pathogenicity of the c.2152del variant and suggest its potential association with a severe early-onset NEDAMSS phenotype. Generalizability remains limited by the small number of cases, and confirmation requires further clinical and functional evidence.