Work

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

Year: 2026

Type: article

Abstract: Background While numerous copy number variations (CNVs) associated with global developmental delay (GDD) have been extensively studied, CNVs on chromosome 2p remain underreported and poorly understood, particularly those involving the EIF2AK2 gene at 2p22.2. This study presents a novel case of pure partial tetrasomy and trisomy of 2p, advancing the understanding of genotype-phenotype correlations in this chromosomal region. Case presentation We present a 7-year-old male who presented with GDD, primarily affecting motor and language skills. Initial symptoms included poor balance and exercise tolerance at 15 months, followed by mild dysarthria and an abnormal gait at 3 years. Physical examination revealed high-set ears, ear leakage, and flat feet. Cranial MRI indicated ventriculomegaly, hypomyelination, and white matter volume loss. Genetic analysis identified two adjacent de novo copy-number gains at chromosome band 2p22.2, one showing tetrasomy and the other trisomy, resulting in a complex genomic amplification involving the EIF2AK2 gene. Whole Exome Sequencing (WES) and Chromosome Analysis by Medium Coverage Whole Genome Sequencing (CMA-seq) confirmed the presence of triplication and duplication, which were not present in the proband's parents. This case highlights a rare instance of pure partial tetrasomy and trisomy 2p22.2. Conclusion We report a complex de novo 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 EIF2AK2 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.

Source: Frontiers in Pediatrics

DOI: 10.3389/fped.2026.1755339

Authors: Jun Wang, Xin Duan, Chaolong Xu, Tianyu Song, Danmin Shen, Fang Fang

Institutions: Capital Medical University, Beijing Children’s Hospital

Language: English

Topic: Genomic variations and chromosomal abnormalities

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801