A, Percentage of participants who reported genetic testing with respect to the age of the participant at the time of enrollment in the RI-CART study between 2013 and 2019. Participants aged 10 years and older have a very low rate of the most modern tests such as chromosomal microarray. B, Percentage of participants who reported genetic testing with respect to the calendar year in which the participant received an autism spectrum disorder diagnosis. Error bars indicate 95% CI.
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Moreno-De-Luca D, Kavanaugh BC, Best CR, Sheinkopf SJ, Phornphutkul C, Morrow EM. Clinical Genetic Testing in Autism Spectrum Disorder in a Large Community-Based Population Sample. JAMA Psychiatry. 2020;77(9):979–981. doi:10.1001/jamapsychiatry.2020.0950
Autism spectrum disorder (ASD) is among the most strongly genetic neuropsychiatric conditions, with an increased frequency of rare, deleterious copy number variants and single-nucleotide variants. Because of this, several medical professional societies have recommended offering chromosomal microarray (CMA) testing and Fragile X testing for people with ASD,1 with growing support for exome sequencing as the first-tier genetic test.2 To understand the implementation of genetic testing in a real-world population, we analyzed data from the Rhode Island Consortium for Autism Research and Treatment (RI-CART) study, a large, population-based study of people with ASD.3
This study was approved by the institutional review board at Lifespan, and all participants provided written informed consent. We analyzed self-report data and medical records, when available, from 1280 participants in the RI-CART study, recruited between April 1, 2013, and April 30, 2019, with ASD diagnosis confirmed by assessment using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).3 Statistical analyses included Pearson correlations, χ2 analyses, and analyses of variance. Statistical significance was set at a 2-sided P value less than .05.
Of these 1280 participants with confirmed ASD diagnosis by ADOS-2, ages ranged from 1.75 years to 68.48 years, and 16.5% (n = 211) reported having received some genetic testing, as follows: Fragile X in 13.2% (n = 169), karyotype in 7.2% (n = 92), and CMA in 4.5% (n = 57). Remarkably, only 3% of participants (n = 39) reported having received both recommended tests (Fragile X and CMA); 9.4% (n = 121) reported that they were unsure whether they had received any testing; and 21.4% did not answer (n = 274).
We next examined factors associated with receiving genetic testing. Participants who reported any genetic testing showed an earlier age at ASD diagnosis (mean age, 4.2 years; range, 1.33-27.1 vs 6.1 years; range, 1.2-51.0; F1,597 = 13.258; P < .001), greater ASD severity (mean [SD] ADOS-2, 7.33 [1.8] vs 6.99 [1.8]; F1,1169 = 5.583; P = .02), and higher frequency of intellectual disability (odds ratio, 3.327; 95% CI, 2.382-4.649; P < .001) and epilepsy (odds ratio, 3.093; 95% CI, 1.748-5.474; P < .001).
We examined factors associated specifically with CMA testing (Table). Patients diagnosed by subspecialist pediatricians were more likely to report genetic testing compared with those diagnosed by psychiatrists and psychologists. Analysis by age at enrollment indicated that younger participants were more likely to report having received CMA testing (Figure, A). Analysis by calendar year of ASD diagnosis indicated that CMA testing increased, and Fragile X and karyotype testing decreased in the last decade (Figure, B). These results reflect changes in genetic testing practices; however, a sustained overall low frequency of genetic testing in the group remains.
This study shows that only 3% of participants reported having undergone the recommended clinical genetic testing for ASD, highlighting a dissonance between professional recommendations and clinical practice. Multiple possible reasons exist for this gap, including (1) participant preferences, although current evidence shows that most parents of people with ASD have favorable attitudes toward genetic testing4,5; and (2) insurance coverage constraints,5 but this has changed after the appearance of medical professional recommendations. Interestingly, we see no difference in CMA testing in participants with and without private insurance but a strong increase in testing in participants with public insurance (Table). Other reasons include (3) limits in clinician knowledge and comfort with genetic testing, with our data showing a lower frequency of genetic testing in people diagnosed with ASD by psychiatrists and psychologists and (4) changes in genetic testing practices over time and a reduced likelihood of adults with ASD being offered testing. Study limitations include that these results were based largely on participant self-report. In conclusion and moving forward, addressing the barriers to testing is crucial to enhance the implementation of genetic testing in clinical practice so that every person with ASD can receive optimal care.
Corresponding Author: Eric M. Morrow, MD, PhD, Laboratories for Molecular Medicine, Brown University, 70 Ship St, Box G-E4, Providence, RI 02903 (firstname.lastname@example.org).
Published Online: May 13, 2020. doi:10.1001/jamapsychiatry.2020.0950
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Moreno-De-Luca D et al. JAMA Psychiatry.
Accepted for Publication: March 8, 2020.
Author Contributions: Drs Moreno-De-Luca and Morrow had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Moreno-De-Luca, Phornphutkul, Morrow.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Moreno-De-Luca, Kavanaugh, Morrow.
Critical revision of the manuscript for important intellectual content: Moreno-De-Luca, Best, Sheinkopf, Phornphutkul, Morrow.
Statistical analysis: Kavanaugh, Morrow.
Obtained funding: Sheinkopf, Morrow.
Administrative, technical, or material support: Moreno-De-Luca, Best, Morrow.
Supervision: Sheinkopf, Phornphutkul, Morrow.
Conflict of Interest Disclosures: Dr Sheinkopf reported grants from Simons Foundation during the conduct of the study. Dr Morrow reported grants from Simons Foundation/Simons Foundation Autism Research Initiative; other support from Norman Prince Neurosciences Institute at Lifespan, Hassenfeld Child Health Innovation Institute at Brown University, and Robert J. and Nancy D. Carney Institute for Brain Science at Brown University during the conduct of the study; and personal fees from Autism Science Foundation, Charles H. Hood Foundation, University of Rochester Medical Center, Eagles Autism Challenge, Simons Foundation/SFARI, Simons Foundation/SPARK Medical Genetics Committee, Foundation Associates, LLC/Autism BrainNet, and the National Institutes of Health outside the submitted work. No other disclosures were reported.
Funding/Support: This work was supported by the Simons Foundation Autism Research Initiative (286756 and 454555), the Norman Prince Neurosciences Institute at Lifespan, the Hassenfeld Child Health Innovation Institute at Brown University, and the Robert J. and Nancy D. Carney Institute for Brain Science at Brown University.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank families who participated in the RI-CART project, Hannah Marsland, BA, Elaine Bucknam, BS, and Molly Goldman, MS, all of Emma Pendleton Bradley Hospital, for technical assistance, and to Hasmik Tokadjian, MS, of Women and Infants Hospital of Rhode Island for technical assistance. The listed individuals received compensation through funding from the Hassenfeld Child Health Innovation Institute at Brown University.
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