Delivering paediatric precision medicine: Genomic and environmental considerations along the causal pathway of childhood neurodevelopmental disorders

Abstract

Precision medicine refers to treatments that are targeted to an individual's unique characteristics. Precision medicine for neurodevelopmental disorders (such as cerebral palsy, attention‐deficit/hyperactivity disorder, obsessive–compulsive disorder, Tourette syndrome, and autism spectrum disorder) in children has predominantly focused on advances in genomic sequencing technologies to increase our ability to identify single gene mutations, diagnose a multitude of rare neurodevelopmental disorders, and gain insights into pathogenesis. Although targeting specific gene variants with high penetrance will help some children with rare disease, this approach will not help most children with neurodevelopmental disorders. A ‘pathway’ driven approach targeting the cumulative influence of psychosocial, epigenetic, or cellular factors is likely to be more effective. To optimize the therapeutic potential of precision medicine, we present a biopsychosocial integrated framework to examine the ‘gene–environment neuroscience interaction’. Such an approach would be supported through harnessing the power of big data, transdiagnostic assessment, impact and implementation evaluation, and a bench‐to‐bedside scientific discovery agenda with ongoing clinician and patient engagement. What this paper adds Precision medicine has predominantly focused on genetic risk factors. The impact of environmental risk factors, particularly inflammatory, metabolic, and psychosocial risks, is understudied. A holistic biopsychosocial model of neurodevelopmental disorder causal pathways is presented. The model will provide precision medicine across the full spectrum of neurodevelopmental disorders.

Current perspectives on perinatal mental health and neurobehavioral development: focus on regulation, coregulation and self-regulation

“…Where such evidence exists, a systems approach should be employed to reduce the research-to-practice-gap. While personalized or precision care is increasingly advocated [196][197][198], this requires both a strong evidence-base, as well as careful implementation of this knowledge [199]. In addition, individuals with 'lived experience' should participate in the process of developing research and moving it into practice [199].…”

Social determinants of health for children with cerebral palsy and their families

“…The causal pathways are likely complex, involving interactions across the biopsychosocial-ecological model. 49 It is imperative for clinicians and researchers to investigate the role of SDH as antenatal risk factors contributing to causal pathways for CP and SDH that influence the ongoing management of CP.…”

Beyond Diagnosis: Preliminary Study of Impact on Children and Parents in Neurodevelopmental Disorders and Juvenile Idiopathic Arthritis-Associated Uveitis

“…Among these chronic diseases, neurodevelopmental disorders (NDDs) are neurologic conditions that impact the development of the brain, characterized by a range of cognitive and behavioral issues. The prevalence of neurodevelopmental disorders is substantial, with an estimated 15% of individuals aged 3 to 17 years in the United States being affected [20] and with an estimated 53 million affected children and young people globally [21]. These abnormalities become evident early and are characterized by impairments in personal, academic, social, and occupational abilities [22,23].…”