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Advanced Neurology Genetics of neurodevelopmental disorders in Mexico

1. Introduction sequencing, has emerged as a pivotal tool in the diagnostic
process, enabling clinicians to identify specific genetic
Neurodevelopmental disorders (NDDs) encompass a abnormalities that may contribute to the disorder. 11,12 It is a
diverse array of conditions that predominantly manifest challenging endeavor to select the appropriate methods to
in early development, often before the child enters grade establish accurate diagnosis. Disease assessment using the
school. These disorders are characterized by developmental right tools not only improves diagnostic accuracy but also
deficits that result in impairments of personal, social, aids in the prediction of disease progression and potential
1
academic, or occupational functioning. The epidemiology comorbidities, and informs therapeutic decision-making.
of NDDs reveals a significant public health concern, with
recent estimates suggesting that they affect >3% of the Moreover, understanding the genetic underpinnings
1
pediatric population worldwide. The prevalence of specific of NDDs offers critical insights for family planning and
NDDs varies, with conditions such as autism spectrum provides families with valuable information regarding
disorder (ASD) and attention deficit hyperactivity disorder recurrence risks. In this era of personalized medicine,
(ADHD) recognized more frequently due to heightened genetic evaluation represents a key step toward tailoring
awareness and diagnostic practices, although intellectual interventions and support to the unique needs of each
disability and communication disorders are common individual, thereby optimizing outcomes and enhancing
clinical presentations. 2,3 the quality of life for those affected by NDDs. This study
Within the intricate spectrum of NDDs, epilepsy aimed to assess the contribution of genetic variations to the
emerges as a significant comorbid condition, featuring clinical presentation of NDDs with comorbidities, such as
a complex interplay between neurodevelopmental epilepsy, in a pediatric cohort based on the Mexican state
4
processes and epileptogenesis. The prevalence of epilepsy of Jalisco.
among individuals with NDDs remains unknown 2. Materials and methods
although studies have consistently shown that certain
genetic mutations associated with NDDs also predispose 2.1. Participants
individuals to epilepsy, suggesting that these conditions Twenty-four pediatric patients and 30 relatives were
may share common mechanisms of neuronal dysfunction included in the present study. Each patient was diagnosed
and altered neural connectivity. Moreover, the onset of with an NDD according to the Diagnostic and Statistical
5
epileptic seizures can exacerbate neurodevelopmental Manual of Mental Disorders (DSM)-V criteria, although
deficits, further complicating the clinical management some of them had other clinical conditions as the main
and prognosis of affected individuals. This bidirectional clinical complaint. All these patients belong to the
6,7
relationship between NDDs and epilepsy necessitates geographical area of the Highlands of Jalisco, located
a comprehensive approach to diagnosis and treatment, in the center-western part of Mexico, and they came to
underscoring the role of integrative care strategies receive multidisciplinary medical attention (pediatric,
combining epileptic and developmental aspects.
neurological, genetic, and rehabilitation) once a month
The etiology of NDDs is multifactorial, involving as part of a non-profit community project operating
complex interactions between genetic, environmental, since 2018 in this locality. The patients’ parents were
8
and neurobiological factors. Advances in genomic informed about possible genetic etiology. A personalized
medicine have identified numerous genetic mutations and genetic panel was indicated according to their clinical,
variations that contribute to the pathophysiology of these electroencephalographic, and neuroimaging findings.
disorders, offering insights into their underlying biological The results received were examined with the literature
9
mechanisms. Environmental factors, including perinatal obtained from PubMed, GeneReviews, GNomad, OMIM,
complications, and early life adversities, also play a critical and ClinVar. Genetic counseling was offered to the family,
role in the development of NDDs; however, it remains and segregation studies were conducted in 11 families and
unclear whether the occurrence of NDDs is a cause of or a 30 relatives who agreed to participate.
10
consequence of the events. Due to the intricate etiological
framework of NDDs, it is of utmost clinical importance to 2.2. Genetic analysis
implement early identification and intervention. Blood samples or oral mucosal swabs were collected,
Given the multifaceted etiology of NDDs and the depending on the patient’s age. Molecular studies were
significant role genetic factors play in their pathophysiology, conducted using next-generation sequencing (NGS)
the importance of genetic evaluation cannot be overstated techniques, adhering to the protocols established by
in cases where an NDD is suspected. Genetic testing, Invitae Corporation (California, USA). Genomic DNA
including chromosomal microarrays and whole exome was isolated and sequenced using Illumina technology

Volume 3 Issue 2 (2024) 2 doi: 10.36922/an.3359