# Decoding _Scn2a_ Variants: Bridging Genetics and Phenotypes in Autism Spectrum Disorder
## 1 Introduction  
Autism spectrum disorder (ASD) is a neurodevelopmental condition defined by a constellation of social communication difficulties and restricted, repetitive behaviors. According to the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V-TR) [1], ASD is defined by persistent deficits in social communication and interaction across multiple contexts; restricted and repetitive patterns of behavior, interests, or activities; symptoms that are present in the early developmental period; clinically significant impairments in social, occupational, or other areas of functioning; and symptoms that are not better explained by intellectual disability or global developmental delay. These criteria also acknowledge the heterogeneity in the clinical presentation of ASD, recognizing that it may occur with or without accompanying intellectual or language impairments, and it can vary in severity based on the level of support required. Importantly, while many individuals with ASD exhibit developmental delays, not all phenotypes follow this trajectory. Recent evidence indicates that some children may not show early developmental concerns but instead exhibit social communication differences or behavioral traits that emerge over time [2]. ASD is a highly heterogeneous condition, with symptoms ranging from mild to severe, affecting individuals differently across the spectrum [3,4]. Additionally, many individuals with ASD exhibit atypical behaviors such as obsessive attachments, hypersensitivity to sensory stimuli, and repetitive actions such as body rocking, hand flapping, and finger flicking [3,5, 6, 7, 8, 9]. These behaviors can significantly impact daily functioning and quality of life, underscoring the importance of early diagnosis and intervention [10, 11, 12]. Early identification is critical for improving outcomes in individuals with ASD. Research shows that those diagnosed at a younger age are more likely to develop higher IQ scores, achieve greater levels of independence, and exhibit better adaptive skills later in life [5,13, 14, 15, 16]. Current interventions include a combination of physical and occupational therapies, alongside tailored medical and behavioral treatments, aimed at addressing the diverse needs of individuals with ASD and their comorbidities [3,17, 18, 19, 20, 21, 22, 23]. Emerging evidence has linked ASD to complex interactions between genetic predispositions and environmental influences, which affect key neurodevelopmental processes such as synaptic signaling, neural connectivity, and brain plasticity. Recent advances in genetic and epigenetic research have begun to uncover the molecular pathways involved in ASD, including disruptions in regulatory networks that shape early brain development [24, 25, 26, 27, 28, 29]. These findings highlight the critical need for a multidisciplinary approach to deepen our understanding of ASD's underlying mechanisms. As ASD diagnoses continue to rise, with approximately 1 in 36 children in the United States affected, it is imperative to advance research into its genetic and epigenetic foundations [30, 31]. Integrating insights from molecular biology, neuroscience, and clinical studies is essential for developing targeted therapies that address the underlying causes of ASD, ultimately improving outcomes and quality of life for individuals with this complex disorder [30]. The etiology of ASD is multifactorial, with many genes contributing to the pathophysiology and prognosis of this condition [30, 32, 33]. An open-access database from the Simons Foundation Autism Research Initiative (SFARI) ([[https://www.sfari.org/resource/sfari-gene](https://www.sfari.org/resource/sfari-gene)]([https://www.sfari.org/resource/sfari-gene](https://www.sfari.org/resource/sfari-gene)), accessed on 16 March 2025) was utilized due to its highly precise and accurate criterion to assess the role of various genes involved in ASD. Gene scoring is used to appraise the strength of correlation between that gene and ASD diagnosis or development risk.