Rapid Electroclinical Evolution in HECW2 ‐Related Developmental and Epileptic Encephalopathy: Report of a Likely Splicing Variant With Familial Transmission

Abstract

The HECW2 gene, essential for neurodevelopment, plays a critical role in maintaining cellular homeostasis and regulating key pathways in the nervous system. Deleterious variants in the HECW2 gene have been associated with developmental delay, intellectual disability, hypotonia, and epilepsy, as well as dysmorphic features.We present the case of an infant with a novel variant in HECW2 with an unusual clinical presentation and a progressive disease course, showing three successive electroclinical patterns, consisting of burst suppression characteristic of early infantile developmental and epileptic encephalopathy, subcontinuous myoclonic seizures, and infantile epileptic spasms syndrome without hypsarrhythmia, occurring over a short period of time. This case expands the clinical spectrum associated with this gene and highlights the intrafamilial phenotypic variability. It also underscores the importance of personalized therapeutic strategies, as demonstrated by the use of perampanel in this patient. These findings emphasize the need to include HECW2 as a possible etiology in the diagnostic evaluation of developmental and epileptic encephalopathies.