The Role of Genetic Testing Among Autistic Individuals.

Abstract

Autism is estimated to have a heritability component of ∼90%.1 This estimate is based on the reported concordance rates of 70% to 90% between monozygotic twins compared with 10% concordance in dizygotic twins.2,3 Furthermore, siblings of autistic individuals carry a >17 times higher likelihood of being on the autism spectrum compared with the general population.3 Although a significant proportion of genetic and molecular mechanisms related to autism remain unclear, researchers have reported findings that suggest both rare Mendelian and polygenic, multifactorial patterns of inheritance. For example, chromosomal microarray testing may identify a genetic etiology in up to 20% of autistic individuals.4,5Given this extent of genetic heritability, large-scale genetic testing and tracking within databases are beneficial in informing both research and clinical practice. The developers of these datasets aim to identify specific gene interactions and assess individual gene contributions while advancing the diagnostic yield of genetic testing.6 The Autism Intervention Research Network on Physical Health genetics research node is poised to help to facilitate the creation of registries for rare and orphan diseases that commonly co-occur with autism. An aim of the Autism Intervention Research Network on Physical Health data repository is to collect this information through the use of data-gathering materials designed to ease the burden on families and support groups wanting to initiate new registries.An important distinction to note is that genetic testing is not used to diagnose autism. An autism diagnosis is based on the presence of defined clinical characteristics. Although genetic test results may reveal the origin of autism in an individual or provide information about the statistical likelihood of being on the autism spectrum, they can also be used to improve the physical health and well-being of autistic individuals by identifying co-occurring medical conditions. Genetic testing may inform a specific diagnosis (eg, fragile X syndrome, Rett syndrome) that could ultimately establish a personalized roadmap for identifying syndrome-associated co-occurring conditions, instituting surveillance, and developing interventions or treatments specific to the genetic etiology. Furthermore, the individual diagnosis may lead to diagnosis-specific community support and help to guide family planning efforts.Despite the American College of Medical Genetics and Genomics establishing fragile X and chromosomal microarray testing as standard-of-care, first-tier tests in the genetic evaluation of autistic individuals,7,8 a surprisingly low number of autistic individuals receive these recommended genetics tests. One recent study with 1280 participants revealed that although 16.5% of participants had some genetic testing done, only 3% had received both recommended tests.9 Moreover, well-documented racial and ethnic disparities exist in the timely identification and genetic screening of autistic individuals. Black, Hispanic/Latinx, and other children of color, particularly those with co-occurring intellectual disabilities, are more likely to have a missed or delayed diagnosis of autism.10–12 Unfortunately, this inequality in the care of autistic individuals, and particularly for Black children, is also observed in the context of genetic screening and counseling.13 Overall, approximately two-thirds of autistic children receive some form of genetic screening and/or counseling; however, Black children are much less likely than their White peers to be offered these services.13 The majority of parents of autistic children actually favor the use of genetic screening and counseling because they believe that the increased knowledge empowers and helps them to intervene earlier than they might have otherwise.14Our goal is to increase awareness regarding the importance and utility of genetic screening and counseling in the lives of autistic individuals and their families. Novel intervention strategies need to be implemented to improve access to such services so that autistic people can be empowered to make informed decisions surrounding the lifestyle interventions and care they wish to pursue.