Sensory Processing Disorders (SPDs) are complex neurodevelopmental conditions characterized by the brain's inability to appropriately interpret and respond to sensory information.

Although commonly observed in children, especially those with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), SPDs are increasingly recognized across age groups.

Recent advances in genetics and neuroimaging have illuminated the biological underpinnings of these disorders, revealing a strong hereditary component with implications for diagnostics and targeted interventions.

Genetic Contributions to Sensory Processing Abnormalities

Multiple twin and family-based studies support a significant genetic contribution to SPDs. A study identified several rare variants and copy number variations (CNVs) strongly associated with sensory modulation dysfunction. These genetic alterations often involve chromosomal regions linked to synaptic development and neural circuit stability.

One of the most prominent genes implicated is GABRB3, located on chromosome 15q11-q13. This gene encodes a subunit of the GABA-A receptor, a crucial regulator of inhibitory signaling in the central nervous system. Mutations or deletions in this region have been associated not only with SPDs but also with ASD and epilepsy, suggesting a shared neuropathological pathway.

The Role of Neurodevelopmental Genes

Genes involved in synaptogenesis and axonal guidance are particularly relevant. For instance, mutations in SHANK3, CNTNAP2, and NRXN1—genes responsible for encoding synaptic scaffolding proteins and adhesion molecules—have been linked to sensory hyper- or hypo-reactivity.

Dr. Michael D. Krystal, a neuropsychiatrist and researcher in neurodevelopmental disorders, states, "Mutations in genes such as SHANK3, CNTNAP2, and NRXN1 disrupt synaptic connectivity, leading to altered sensory processing and heightened sensitivity to tactile and auditory stimuli, which are hallmark features of sensory processing disorders."

Moreover, SCN2A, a gene encoding a voltage-gated sodium channel, has recently emerged as a potential driver of sensory dysregulation. Variants in SCN2A are increasingly detected in children presenting with sensory seeking behaviors, motor planning deficits, and anxiety-related responses to sensory overload.

Genomic Overlap with Neuropsychiatric Conditions

There is considerable overlap in the genetic architecture of SPDs and other neurodevelopmental disorders. Shared molecular pathways involving MECP2, CHD8, and FOXP1—previously identified in autism spectrum research also appear relevant to isolated cases of SPD. This genetic convergence indicates that SPDs may not be distinct conditions but rather phenotypic expressions within a broader neurodevelopmental spectrum.

Dr. Stephan Sanders, a pediatric neurogeneticist, emphasizes that "the sensory features observed in children are often the earliest neurobiological signals of an underlying genomic variant, long before cognitive or behavioral symptoms become apparent."

Epigenetics and Environmental Interactions

While heritability plays a substantial role, gene-environment interactions must also be considered. Epigenetic mechanisms such as DNA methylation and histone modification can alter gene expression without changing the genetic code. Prenatal exposure to stress, inflammation, or certain medications can trigger these modifications, exacerbating sensory processing challenges in genetically susceptible individuals.

A recent paper explored how maternal immune activation during pregnancy modifies the expression of genes like RELN and PTEN, both of which are critical for neuronal migration and cortical organization. The study proposed that these epigenetic shifts may amplify the severity of SPD phenotypes, particularly in early childhood.

Neuroimaging Correlates of Genetic Findings

Genetic studies are increasingly being complemented by advanced neuroimaging techniques, such as diffusion tensor imaging (DTI) and magnetoencephalography (MEG), to identify structural and functional abnormalities in the sensory pathways of affected individuals.

Reduced white matter integrity in the posterior thalamic radiations and superior longitudinal fasciculus has been repeatedly documented in children with confirmed genetic mutations linked to SPDs.

Importantly, these imaging signatures often correlate with specific behavioral traits—such as difficulty with auditory filtering or vestibular processing—suggesting that genetic findings may soon be integrated into a precision medicine model for SPD diagnostics.

Toward Targeted Therapeutics and Early Detection

Understanding the genetic basis of SPDs opens the door to early screening and tailored interventions. Genetic testing panels focusing on high-impact variants (e.g., GABRB3, SHANK3, SCN2A) are under development, aimed at identifying at-risk infants even before sensory behaviors fully manifest.

Emerging therapies include molecular agents that modulate ion channel function and synaptic plasticity. For example, preclinical studies of oxytocin receptor modulators and GABAergic agents are showing promise in normalizing sensory responsiveness in animal models with specific genetic alterations.

The genetic underpinnings of Sensory Processing Disorders are becoming clearer through a convergence of genomic research, neurodevelopmental studies, and neuroimaging techniques. Identifying key genes and their expression patterns enables clinicians and researchers to refine diagnostic tools and develop personalized interventions.

As the field evolves, a biologically informed model of SPD will not only demystify the condition but also transform its clinical management, ensuring better outcomes for affected individuals.