Wendy R. Uhlmann

Recommendations for Returning Genomic Incidental Findings? We Need to Talk!

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines.Genet Med 15 11, 854–859.Genetics in Medicine (2013); 15 11, 854–859. doi:10.1038/gim.2013.113

Mild cognitive impairment in clinical care: a survey of American Academy of Neurology members.

Objective: To assess how neurologists view mild cognitive impairment (MCI) as a clinical diagnosis and how they treat patients with mild cognitive symptoms. Methods: Members of the American Academy of Neurology with an aging, dementia, or behavioral neurology practice focus were surveyed by self-administered questionnaire. Results: Survey respondents were 420 providers (response rate 48%), and 88% reported at least monthly encounters with patients experiencing mild cognitive symptoms. Most respondents recognize MCI as a clinical diagnosis (90%) and use its diagnostic code for billing purposes (70%). When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%) and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of findings (15%). Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other agents (e.g., vitamin E) prescribed less frequently. Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2) motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%). Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer disease (21%); and 3) diagnosis can cause unnecessary worry (20%). Conclusions: Patients with mild cognitive symptoms are commonly seen by neurologists, who view MCI as a useful diagnostic category. Information and treatments provided to patients with MCI vary significantly, suggesting a need for practice guidelines and further research on clinical decision-making with this population.

Willingness to pay for genetic testing for Alzheimer's disease: a measure of personal utility.

BACKGROUND The increased availability of genetic tests for common, complex diseases, such as Alzheimers disease (AD), raises questions about what people are willing to pay for these services. METHODS We studied willingness-to-pay for genetic testing in a study of AD risk assessment that included APOE genotype disclosure among 276 first-degree relatives of persons with AD. RESULTS Seventy-one percent reported that they would ask for such testing from their doctor if it were covered by health insurance, and 60% would ask for it even if it required self-pay. Forty-one percent were willing to pay more than

Report from the National Society of Genetic Counselors Service Delivery Model Task Force: A Proposal to Define Models, Components, and Modes of Referral

100 for testing, and more than half would have been willing to pay for the test out of pocket. Participants who learned that they were APOE ε4 positive and those who had higher education were less likely to want testing if covered by insurance, possibly to avoid discrimination. CONCLUSION This is the first report to examine willingness to pay for susceptibility genetic testing in a sample of participants who had actually undergone such testing. These findings reveal that some participants find valuable personal utility in genetic risk information even when such information does not have proven clinical utility.

Guidelines for Writing Letters to Patients

The Service Delivery Model Task Force (SDMTF) was appointed in 2009 by the leadership of the National Society of Genetic Counselors (NSGC) with a charge to research and assess the capacity of all existing service delivery models to improve access to genetic counseling services in the context of increasing demand for genetic testing and counseling. In approaching this charge, the SDMTF found that there were varying interpretations of what was meant by “service delivery models” and the group held extensive discussions about current practices to arrive at consensus of proposed definitions for current genetic service delivery models, modes of referral and components of service delivery. The major goal of these proposed definitions is to allow for conversations to begin to address the charge to the committee. We propose that current models of service delivery can be defined by: 1) the methods in which genetic counseling services are delivered (In-person, Telephone, Group and Telegenetics), 2) the way they are accessed by patients (Traditional referral, Tandem, Triage, Rescue and Self-referral) and 3) the variable components that depend upon multiple factors unique to each service setting. This report by the SDMTF provides a starting point whereby standardized terminology can be used in future studies that assess the effectiveness of these described models to overcome barriers to access to genetic counseling services.

Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing

Patient letters provide a permanent record of the genetic counseling that was provided and are unique in medical care; rarely do other health care providers send summaries written specifically to their patients and families. We surveyed genetic counseling training program directors and found that while the acquisition of patient letter-writing skills was considered important, there were no specific guidelines made available to students. To develop letter-writing guidelines, we evaluated patient letters, reviewed references on professional correspondence, surveyed the medical literature, and worked with a writing consultant. The guidelines we subsequently developed and present here include a format for writing patient letters, suggestions on presenting medical information in understandable terms, and wording considerations. These patient letter-writing guidelines are intended to serve as a guide for teaching students this important skill and as a resource for practicing health care professionals.

How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study.

BACKGROUND Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP). OBJECTIVE To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP. DESIGN Longitudinal, prospective cohort study. SETTING Online survey before and 6 months after results. PARTICIPANTS DTC PGT consumers. MEASUREMENTS Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCPs understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses. RESULTS Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%). LIMITATION Participants may not be representative of all DTC PGT consumers. CONCLUSION A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve. PRIMARY FUNDING SOURCE National Institutes of Health.

Changes to perceptions of the pros and cons of genetic susceptibility testing after APOE genotyping for Alzheimer disease risk.

Aim: To assess customer comprehension of health-related personal genomic testing (PGT) results. Methods: We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimers disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. Results: Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1-97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6-74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥60 years) was associated with lower comprehension scores. Conclusions: Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics.

Ehlers–Danlos syndrome, hypermobility type: A characterization of the patients' lived experience

Purpose: Perceptions about the pros and cons of genetic susceptibility testing are among the best predictors of test utilization. How actual testing changes such perceptions has yet to be examined.Methods: In a clinical trial, first-degree relatives of patients with Alzheimer disease received genetic risk assessments for Alzheimer disease including APOE disclosure. Participants rated 11 possible benefits associated with genetic testing (pros) and 10 risks or limitations (cons) before genetic risk disclosure and again 12 months afterward.Results: Pros were rated higher than cons at baseline (3.53 vs. 1.83, P < 0.001) and at 12 months after risk disclosure (3.33 vs. 1.88, P < 0.001). Ratings of pros decreased during the 12-month period (3.33 vs. 3.53, P < 0.001). Ratings of cons did not change (1.88 vs. 1.83, P = 0.199) except for a three-item discrimination subscale which increased (2.07 vs. 1.92, P = 0.012). Among specific pros and cons, three items related to prevention and treatment changed the most.Conclusion: The process of APOE genetic risk assessment for Alzheimer disease sensitizes some to its limitations and the risks of discrimination; however, 1-year after disclosure, test recipients still consider the pros to strongly outweigh the cons.

Direct-to-Consumer Genetic Testing: User Motivations, Decision Making, and Perceived Utility of Results

Hypermobility type Ehlers–Danlos syndrome (EDS‐HT) is an inherited connective tissue disorder clinically diagnosed by the presence of significant joint hypermobility and associated skin manifestations. This article presents a large‐scale study that reports the lived experience of EDS‐HT patients, the broad range of symptoms that individuals with EDS‐HT experience, and the impact these symptoms have on daily functioning. A 237‐item online survey, including validated questions regarding pain and depression, was developed. Four hundred sixty‐six (466) adults (90% female, 52% college or higher degree) with a self‐reported diagnosis of EDS‐HT made in a clinic or hospital were included. The most frequently reported symptoms were joint pain (99%), hypermobility (99%), and limb pain (91%). They also reported a high frequency of other conditions including chronic fatigue (82%), anxiety (73%), depression (69%), and fibromyalgia (42%). Forty‐six percent of respondents reported constant pain often described as aching and tiring/exhausting. Despite multiple interventions and therapies, many individuals (53%) indicated that their diagnosis negatively affected their ability to work or attend school. Our results show that individuals with EDS‐HT can experience a wide array of symptoms and co‐morbid conditions. The degree of constant pain and disability experienced by the majority of EDS‐HT respondents is striking and illustrates the impact this disorder has on quality of life as well as the clinical challenges inherent in managing this complex connective tissue disorder.