How copy number variations shape brain developmental disorders: unravelling the synaptic puzzle

Neurodevelopmental disorders (NDDs), such as schizophrenia (SCZ), Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning disabilities, and intellectual disabilities (ID), are highly prevalent. One significant genetic factor associated with NDDs is copy number variations (CNVs), which are structural changes in the genome that involve deletions or duplications of DNA segments. CNVs are known to significantly elevate the risk of developing NDDs and are increasingly being studied for their role in these conditions. While CNVs encompass a wide range of genetic alterations, emerging evidence suggests they may disrupt key biological processes, such as synaptic development and function in the brain, which are critical for learning and behaviour. This review synthesizes findings from genetics, molecular biology, and related fields to explore the link between CNVs and synaptic pathology with therapeutic investigations. By understanding how CNVs compromise synaptic function, we identify paths to more targeted and effective therapies for neurodevelopmental disorders associated with CNVs.