Challenges and Errors in Genetic Testing

Abstract

PurposeIn this ongoing case series, 33 genetic testing cases are documented in which tests were recommended, ordered, interpreted, or used incorrectly and/or in which clinicians faced challenges related to history/reports provided by patients or laboratories.MethodsAn invitation to submit cases of challenges or errors in genetic testing was issued to the general National Society of Genetic Counselors Listserv, the National Society of Genetic Counselors Cancer Special Interest Group members, as part of a case series with Precision Oncology News, and via social media (i.e., Facebook, Twitter, LinkedIn). Deidentified clinical documentation was requested and reviewed when available. Thirty-three cases were submitted, reviewed, and accepted. A thematic analysis was performed. Submitters were asked to approve cases before submission.ResultsAll cases took place in the United States, involved hereditary cancer testing and/or findings in cancer predisposition genes, and involved medical-grade genetic testing, direct-to-consumer testing, or research genetic testing. In 9 cases, test results were misinterpreted, leading to incorrect screening or risk-reducing procedures being performed/recommended. In 5 cases, incorrect or unnecessary testing was ordered/recommended. In 3 cases, incorrect clinical diagnoses were made, or opportunities for diagnoses were delayed. In 3 cases, errors or challenges arose related to medical intervention after testing or reported genetic diagnosis. In 2 cases, physicians provided incorrect information related to the inheritance pattern of a syndrome. In 2 cases, there were challenges related to the interpretation of genetic variants. In 2 cases, challenges arose after direct-to-consumer testing. One case involved test results that should never have been reported based on sample quality. In 1 case, a patient presented a falsified test result. In 5 cases, multiple errors were made.DiscussionAs genetic testing continues to become more complicated and common, it is critical that patients and nongenetics providers have access to accurate and timely genetic counseling information. Even as multiple medical bodies highlight the value of genetic counselors (GCs), tension exists in the genomics community as GCs work toward licensure and Medicare provider status. It is critical that health care communities leverage, rather than restrict, the expertise and experience of GCs so that patients can benefit from, and not be harmed by, genetic testing. In order to responsibly democratize genomics, it will be important for genetics and nongenetic health care providers to collaborate and use alternative service delivery models and technology solutions at point of care. To deliver on the promise of precision medicine, accurate resources and tools must be utilized.

Critical components of genomic medicine practice for non‐genetics healthcare professionals: Genetic counselors' perspectives and implications for medical education

“…In addition to self-reported confidence by NGHPs, gaps in the genetics/genomics knowledge and clinical practices of NGHPs have been observed (Dekanek et al, 2020;Hamilton et al, 2017;Vadaparampil et al, 2015). These gaps in knowledge or clinical practice of NGHPs can result in adverse medical, psychological, and financial events for patients and their families due to inaccurate ordering, misinterpretation of results, or inadequate genetic counseling (Bensend et al, 2014;Brierley et al, 2012;Farmer et al, 2019Farmer et al, , 2021. Although limited, there have been some data published on differential outcomes between genetic services provided by NGHPs or genetic professionals, showing that NGHPs may miss opportunities for genetic testing or referrals or that pretest counseling discussions with GCs are more comprehensive and result in better patient recall of discussed information (Cragun et al, 2015;Truong et al, 2021).…”

“…Unfortunately, gaps in genetics/genomics knowledge can lead to medical errors such as ordering the incorrect test, misinterpreting test results, incorrectly assuming a variant completely explains a family history of cancer, or providing inadequate information about genetic test results (Farmer et al, 2019(Farmer et al, , 2021. Errors like these can lead to adverse events with negative medical, ethical, and financial implications for patients and their relatives such as incorrect medical management recommendations or misuse of healthcare resources (Brierley et al, 2012).…”

The VUS Challenge in Cystic Kidney Disease: A Case-Based Review

“…Because there is a temptation to overattribute disease causation to missense variants, 23 ongoing collaboration with genetics experts is necessary to prevent errors. [24][25][26] If our pretest probability is high for ADPKD and a VUS in a cystic kidney gene is found, then we begin by analyzing the variant prevalence. The allele frequency of a significant disease-causing variant will be rare.…”

Stagnation in quality of next‐generation sequencing assays for the diagnosis of hereditary hematopoietic malignancies

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Genetic counselors have traditionally been the health care providers responsible for the ordering of genetic tests, but the number of other health care providers who now order and interpret genetic tests has increased exponentially as the availability of genetic testing has increased over the past decade (George et al, 2016;Rahman, 2014;Valencia et al, 2017). These other health care providers, with little to no genetics training, often rely on the laboratory themselves to provide the most up-to-date, scientifically sound assays (Farmer et al, 2021;Ramos & Weissman, 2018).Hereditary hematopoietic malignancies (HHMs) are hereditary blood cancer syndromes driven by germline pathogenic/likely pathogenic (P/LP) variants. Although research regarding HHMs is relatively new, all HHMs to date have followed Mendelian inheritance patterns .

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