A Personalized Precision Approach to Autism Spectrum Related Disorders

In spite of the shared features as listed in DSM-5, there are more than 150 known etiologies of Autism Spectrum -that influence severity, comorbidities, and treatment response. We need to design a more personalized approach to autism, relating risk factors (genetic and environmental) and biomarkers to phenotypes, outcomes and treatments.
Challenges: Liability to ASD is now understood to be due in part to rare genetic variants and in part to environmental causes. Recent data based on WES shows that in eighty percent of cases there is a genetic finding. Additional major challenges are early diagnosis and the highly elevated risk in siblings.
Our data of 1500 families was analyzed in terms of etiology.
Discussion:
In addition to multiple single gene findings the most common inherited etiology is Fragile X and the most significant non- genetic etiology was prematurity and perinatal brain injury. Gender plays an important role in the determination of specific trajectories.
Conclusion:
The pathways derive from a multitude of etiologies may result in directing treatment- either of the core symptoms or of the comorbidities. Findings indicate that a stable diagnosis can be made by 14 months and optimal outcomes are most assured in children who receive early intervention. As a result, it is critical to explore methods that may be used to augment ASD risk recognition in an objective, rapid, and reliable manner and as early as possible using genetic and epigenetic predisposition methods. The path from etiology to treatment can be demonstrated using Fragile X syndrome as a model of the path from etiology through phenotype, to epigenetic- targeted treatment. Gender, prematurity/ perinatal, familial and prenatal development can be used to calculate risk, to design a more targeted apprach and to intervene earlier.