SU46 - PSYCHIATRIC GENETIC COUNSELING: CHALLENGES IN AUTISM SPECTRUM DISORDERS

Abstract

Autism Spectrum Disorders (ASD) have one of the highest estimates of heritability among psychiatric conditions. Genetic testing is now considered standard of care for diagnosis of ASD etiology, and is increasingly available, affordable, and offered to patients and their families. The 2013 American College of Medical Genetics Practice Guidelines estimates a genetic diagnostic yield of 30–40% in ASD cases, recommending Chromosome Microarray (CMA), single gene testing such as FMR1, as well as other testing such as metabolic studies. As of 2017, more than 20 academic and commercial laboratories have developed clinical genetic tests specific for ASD, which are being marketed as diagnostic testing to clinicians worldwide. However, these gene panels often have low clinical validity, and often include genes where the associations between the loci and ASD are unclear. Little is known regarding the practical experience of individuals with ASD undergoing genetic testing. Here, we present five illustrative cases and suggest standardized approaches for genetic counseling in ASD. Since 2013, clinical genetic testing has been routinely offered to individuals with ASD in our Genetics clinic. The most common test offered was CMA, followed by FMR1 and whole exome sequencing. Through retrospective chart review, five representative cases were selected to highlight the diagnostic and counseling complexities. From 2013 to 2016, we provided genetic counseling to 29 individuals with ASD, resulting in at least a partial genetic diagnosis in 34% of cases, a variant of unknown significance in 10% of cases, and incidental findings in 7% of cases. We present five cases of nonsyndromic ASD with variable genetic testing results (1q21.1 deletion, 16p11.2 duplication, 15q13.3 duplication, AUTS2, 47, XYY) and discuss the genetic counseling issues for each. In our collective experience with these and other cases, we have found that diagnostic challenges include phenotypic and locus heterogeneity, variable expressivity, reduced penetrance, causative versus risk alleles, and changing genetic associations as research progresses. Psychosocial challenges include misleading information online, illness representation beliefs of patients and families, stigma, guilt and shame, and family communication. It is not enough to know that certain genetic factors are associated with ASD. Translating this information in a meaningful way for patients and families is the ultimate goal of all clinically-directed research. The reactions of the families described in this case series illustrate these challenges. We recommend standardizing informed consent for genetic testing in ASD, especially regarding the inherent uncertainties, and to include referral to a clinical genetic specialist if available. Careful and informed genetic counseling is crucial and may lead to improved coping and adaptation, and may reduce negative consequences of stigma and discrimination.