Unraveling genetic contributions to neurodevelopmental disorders and epilepsy in a pediatric cohort from a Mexican state

Abstract

Neurodevelopmental disorders (NDDs) encompass a broad spectrum of conditions that significantly impact personal, social, academic, or occupational functioning from an early age. Epilepsy emerges as a significant comorbid condition, featuring a complex interplay between neurodevelopmental processes and epileptogenesis, likely rooted in genetic abnormalities. This research is a descriptive observational study designed to assess the contribution of genetic variations to the clinical presentation of NDDs in a pediatric population from the Mexican state of Jalisco, aiming to enhance diagnostic and management strategies. The patients underwent comprehensive clinical evaluations and personalized genetic testing using next-generation sequencing techniques, and their relatives were studied only on a case-by-case basis if information regarding the mode of inheritance was needed. This study included 24 patients and 30 relatives. Diagnoses of Mendelian inheritance diseases were identified in 14 patients, including cases with mutations not previously associated with NDDs. Genetic testing revealed a variety of pathogenic and likely pathogenic mutations, as well as variants of uncertain significance, across a range of genes implicated in NDDs. Notable findings included new mutations related to low-prevalence genetic syndromes and the identification of both inherited and de novo mutations contributing to the neurodevelopmental phenotypes observed. Our findings underscore the complex genetic landscape of NDDs and epilepsy, highlighting the crucial role of genetic evaluation in elucidating the etiology of these disorders within the studied population. The integration of genetic testing into the diagnostic process for NDDs not only facilitates a more precise diagnosis but also informs prognostic outlooks and guides tailored intervention strategies. Moreover, this study advocates for the continued exploration of genetic underpinnings in NDDs to further refine diagnostic accuracy, improve therapeutic approaches, and support familial decision-making, and emphasizing the importance of genetics in advancing neurodevelopmental medicine.