The Impact of 8p23 Copy Number Variations on Neurodevelopmental Aetiology: A Focus on Rare Deletions

Copy number variations (CNVs) involving the 8p23 chromosomal region have been increasingly associated with neurodevelopmental disorders (NDDs); however, the distal 8p23.1-p23.3 subregion remains poorly characterized. This study aimed to describe the clinical and genomic features of paediatric patients with rare 8p23 CNVs and to explore potential genotype-phenotype associations within a case-series framework.

Five unrelated paediatric patients aged 1-12 years who were evaluated for NDDs were identified as carriers of rare 8p23 CNVs. Genomic investigations included conventional karyotyping, chromosomal microarray analysis (CMA) and whole-exome sequencing (WES). Segregation analyses were performed in available parents to assess inheritance patterns. This study was designed as a descriptive case series and should be considered exploratory and hypothesis-generating in nature.

All patients harboured heterozygous deletions within the 8p23 region and exhibited heterogeneous neurodevelopmental phenotypes, including attention-deficit/hyperactivity disorder, autism spectrum disorder and global developmental delay. Deletions involving CSMD1 and DLGAP2 may contribute to neuropsychiatric features, whereas a larger multigenic deletion encompassing ARHGEF10 was associated with more severe global developmental impairment. An isolated deletion of TDRP was identified in a patient with attention-deficit/hyperactivity disorder, suggesting a possible contributory role in neurobehavioral phenotypes. A focal deletion affecting the FAM90A gene family was detected in a patient presenting with febrile seizures and short stature.

These findings highlight the marked phenotypic variability associated with rare 8p23 CNVs and underscore the importance of detailed genomic profiling in NDDs. Gene-specific microdeletions may contribute to distinct clinical phenotypes, while larger deletions appear to be associated with more severe developmental outcomes. However, given the case-series design and the presence of variants of uncertain significance, the findings should be interpreted with caution. Further studies in larger cohorts and functional analyses are warranted to clarify the roles of TDRP and FAM90A.