Complex de novo tetrasomy and trisomy of 2p22.2 involving EIF2AK2 in a child with global developmental delay: a case report and literature review

We report a complex <i>de novo</i> gain involving adjacent tetrasomy and trisomy segments at the 2p22.2 locus. Although formally classified as a Variant of Uncertain Significance (VUS) due to the lack of established dosage-sensitive genes, the involvement of <i>EIF2AK2</i> suggests a potential pathogenic mechanism. We propose that the increased genomic dosage may trigger dysregulation of the integrated stress response (ISR) via a concentration-dependent gain-of-function effect, mirroring the phenotype of pathogenic point variations.