Accepting or declining preconception expanded carrier screening: An exploratory study with 407 couples.

Rapidly evolving genomic technologies have made genetic expanded carrier screening (ECS) possible for couples considering a pregnancy. The aim of ECS is to identify couples at risk of having a child affected with a severe disorder and to facilitate their reproductive decision-making process. The ECS test we offer at our center, called BeGECS (Belgian Genetic ECS), consists of 1268 autosomal recessive (AR) and X-linked pathogenic genes, including severe childhood-onset disorders. However, thus far data are scarce regarding the actual uptake of preconception ECS in a clinical setting. Therefore, our aim was to describe the characteristics of 407 couples to whom ECS was offered at the Center for Medical Genetics of the University Hospital Ghent (CMGG). In addition, we aimed to identify their reasons for accepting or declining BeGECS. Between October 2019 and January 2023, 407 preconception couples were offered BeGECS and were asked to fill in a questionnaire after their decision. Of the 407 couples participating in the survey, 270 (66%) decided to take the test and 137 (34%) declined. We observed that age, highest education level as well as indication for consultation were statistically different between the group that accepted to take the test and the group that declined (p = 0.037). In particular, age and education level were substantially higher in the group that accepted the test. Major reasons for taking BeGECS include prevention, wishing to obtain all information possible, helping preparing their future reproductive decision and increasing their sense of control by being informed. However, couples that do not chose to take BeGECS stated that too much information would make them anxious, that the result would not change their decision to have children, that they do not want to spend money on something that will not happen and that they do not worry about their family history. These findings show that the majority of preconception couples that were offered ECS, accepted the test.

Development and assessment of educational materials for spinal muscular atrophy carrier screening in the Plain community.

Spinal muscular atrophy (SMA) has been reported in both Amish and Mennonite (Plain) communities, and a higher incidence has been observed in certain Mennonite communities compared to the general population. There are several therapies for SMA, but all are most effective in pre-symptomatic newborns. To identify couples from the Wisconsin Plain community who are most likely to have a child with SMA, carrier screening is offered via mailed kits with at-home specimen collection. Our survey data about Plain families' perspectives on genetic testing suggest educational materials are needed for individuals providing informed consent with at-home specimen collection. We therefore developed a Plain population-specific educational trifold brochure about SMA carrier screening by incorporating existing medical education strategies and feedback from Plain community members and their health care providers. Along with the brochure, surveys were included in the kits to assess baseline knowledge about SMA carrier screening ("pre-education") as well as improvement in knowledge after reviewing the brochure and cultural appropriateness of the brochure ("post-education"). Fifty-five testing kits were distributed, and 26 survey pairs (pre- and post-education) were returned and analyzed (response rate 47%). Respondents had high baseline knowledge with an average of 5 of 7 questions (71%) answered correctly on the pre-education survey. Knowledge improved after reviewing the brochure as the average score increased to 6.5 of 7 questions (93%) answered correctly. Questions about risks of having an affected child after positive or negative carrier screening showed the most improvement from the pre-education to post-education surveys. Most respondents indicated the brochure was helpful, was easy to understand, and contained the right amount of information. Overall, incorporating elements of existing medical education strategies with feedback from the target population and stakeholders about appropriate language seems to be an effective method for creating beneficial, culturally responsive educational materials for the Plain population.

Understanding the psychological impact of identifying carrier status on young adults: A qualitative study exploring peer reactions.

The benefits and harms of identifying carriers in childhood have long been debated with European Guidelines advising against this practice. Yet over a thousand carriers are identified via newborn bloodspot screening per year in the United Kingdom alone. One of the concerns about identification is the impact it has on an individual's identity. This, in part, will be determined by how parents and peers view carriers, particularly during young adulthood. To address the paucity of research looking at how carriers are perceived by peers, this study sought to explore the views of young adults, who themselves are not carriers, toward carriers. As the narratives around COVID-19 increased, the salience of the term "carrier", the impact of such narratives on perceptions, was also explored. Twenty-five 18-25 year olds participated in a diary-interview study in the United Kingdom during 2021 to explore their perceptions of carriers via hypothetical scenarios. Data were analyzed using thematic analysis. Interviewees believed carriers would experience stigma-including societal and self-stigma. This was because people used existing illness beliefs to make sense of carrier status about which they had low levels of understanding. Interviewees believed carriers would experience challenges in familial and romantic relationships due to others' judgments. They also believed parents of carriers would experience a burden around making reproductive decisions, with clear views on what society would view as acceptable choices. Importantly interviewees felt knowledge of ones' own carrier status conferred complex communication challenges within relationships. These findings suggest an urgent need for more research and support for young adults entering a key stage in life for identity formation who have knowledge of their carrier status. The results suggest that support targeted toward the carrier regarding navigating complex communication and targeted more broadly to avoid stigma based on misunderstanding should be researched and developed.

Human Genetics Society of Australasia Position Statement: Genetic Carrier Testing for Recessive Conditions.

This Position Statement provides guidelines to assist all health professionals who receive requests for carrier testing and laboratory staff conducting the tests.In this Statement, the term 'carrier testing' refers to genetic testing in an individual to determine whether they have inherited a pathogenic variant associated with an autosomal or X-linked recessive condition previously identified in a blood relative. Carrier testing recommendations: (1) Carrier testing should only be performed with the individual's knowledge and consent; (2) An individual considering (for themselves, or on behalf of another) whether to have a carrier test should be supported to make an informed decision; (3) The mode of inheritance, the individual's personal experience with the condition, and the healthcare setting in which the test is being performed should be considered when determining whether carrier testing should be offered by a genetic health professional. Regarding children and young people: Unless there is direct medical benefit in the immediate future, the default position should be to postpone carrier testing until the child or young person can be supported to make an informed decision. There may be some specific situations where it is appropriate to facilitate carrier testing in children and young people (see section in this article). In such cases, testing should only be offered with pre- and post-test genetic counseling in which genetic health professionals and parents/guardians should explore the rationale for testing and the interests of the child and the family.

Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors.

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable. This practice guideline provides evidence-based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer-reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at-risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity-based carrier screening alternative which does not rely on race-based medicine. The final decision to pursue carrier screening should be directed by shared decision-making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity-based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race-based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.

An exploration of knowledge, risk perceptions, and communication in a family with multiple genetic risks for Parkinson's disease.

Genomic testing increasingly challenges health care providers and patients to understand, share, and use information. The provision of polygenic risks is anticipated to complicate comprehension, communication, and risk perception further. This manuscript aims to illuminate the challenges confronting families with multiple genetic risks for Parkinson's disease. Identifying and planning for such issues may prove valuable to family members now and in the future, should neuroprotective or genotype-specific therapies become available. We present qualitative data from interviews with a multi-generational family carrying pathogenic variants in the glucocerebrosidase (GBA1) and leucine-rich repeat kinase 2 (LRRK2) genes which are associated with an increased risk for developing Parkinson's disease (PD). The family includes two brothers (heterozygous for LRRK2 p.G2019S and homozygous for GBA1 p.N409S) and their four descendants. The brothers were concordant for GD and discordant for PD. Genetic counseling and testing were provided to four of the six participants. Two years later, semi-structured interviews were conducted with the initial participants (n = 4) and two additional first-degree relatives. Interviews were transcribed and thematically analyzed, providing the basis for this report. Illuminated topics include the perceived risk of developing PD, recall of genetic information, and family communication. With the expanding use of exome and genome sequencing, we anticipate that genetic counselors will increasingly face the challenges demonstrated by this case involving multiple genetic risks for PD, limited data to clarify risk, and the inherent variability of family communication, genetic knowledge, and risk perception. This clinical case report provides a compelling narrative demonstrating the need for additional research exploring these multifaceted topics relevant to both families facing these challenges and providers striving to assist, support and guide their journey.

Factors associated with US and Canadian genetic counselors' testing decisions during pregnancy.

Decision-making regarding prenatal screening and diagnostic testing has become more complex as the number of options has increased, with pregnant patients having access to more information about their pregnancies than ever before. Genetic counselors have extensive training in prenatal genetic screening and testing options, but personal decision-making in this well-informed population remains largely unstudied. This study describes the prenatal testing decisions genetic counselors made during their own pregnancies, and the factors identified as important when making those decisions. A web-based, mixed-methods survey was distributed to members of multiple professional societies for genetic counselors. A total of 318 genetic counselors across numerous specialties in the United States and Canada participated in this study. The satisfaction with decision scale was modified and applied to measure participants' decisional satisfaction. In their most recent pregnancies, most genetic counselors pursued carrier screening (77%) and aneuploidy and/or open neural tube defect screening (88%). A minority of genetic counselors (15%) utilized diagnostic testing. Common factors considered when making testing decisions included wanting information that could impact future decisions, test specifics (e.g., accuracy, methodology, and content), and knowledge gained from participants' genetic counseling background. The uptake of diagnostic testing among prenatal genetic counselors was significantly greater (p < 0.05) than the uptake among genetic counselors in other specialties. This informed study population largely self-directed their own prenatal care, leading to high satisfaction with their decisions. Data in this study provide evidence for promoting participation in prenatal screening and testing decision-making to maximize decisional satisfaction.

Evolving approaches to prenatal genetic counseling for Spinal Muscular Atrophy in the new treatment era.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease characterized by muscle weakness and atrophy with usually typical cognition. The first disease-modifying therapy for SMA, nusinersen, was approved by the United States Food and Drug Administration (FDA) in 2016 and leads to improved outcomes, especially when administered presymptomatically. Population-wide carrier screening and newborn screening (NBS) are now recommended by several professional organizations to promote reproductive autonomy, early diagnosis, and treatment. Prenatal genetic counselors (GCs) are important providers of the SMA screening and diagnosis process, but the possible impact of nusinersen on their practice has not been explored. A survey of 182 prenatal GCs in the United States (US) assessed baseline knowledge of nusinersen and likelihood of discussing this option with prospective parents. The majority of GCs (94.5%) were aware of this drug, and almost all (87.3%) felt that this information would affect pregnancy management decisions. However, less than half of GCs (49.2%) felt confident discussing nusinersen, 45.1% were unaware if this treatment was available in their practice setting, and one in five (19.3%) did not know where to find information about SMA treatments. Participants were more confident and knowledgeable about NBS for SMA, and several indicated that NBS would reduce their emphasis on carrier screening and diagnostic testing, not recognizing that an early prenatal diagnosis can enable preparations for complex, time-sensitive treatment. Only 5.0% of participants felt that a prenatal GC should discuss nusinersen with prospective parents. However, encouragingly, nearly all GCs who felt confident discussing this treatment option (86.4%) reported using this information weekly in their real-world practice. These data highlight an opportunity to provide up-to-date education about SMA treatments, as well as the significant impacts of early diagnosis. Additionally, interdisciplinary communication and care may be appropriate to clarify healthcare resources available and support a variety of patient needs. Increasing awareness and confidence about available options can help prenatal GCs empower patient autonomy and shared decision-making in the new era of disease-modifying treatment for SMA.

Evaluating the experiences of individuals with personal health risks identified through expanded carrier screening.

Expanded carrier screening (ECS) is used to identify individuals and couples at risk for having children with recessive or X-linked genetic conditions; however, personal health risks (PHR) can also be identified through this testing. There is limited data on how genetic counseling regarding PHR from ECS is perceived by the individual, or how they use this information. This study quantitatively surveyed individuals identified with these risks between September 2013 and March 2020. The 30-item survey included the validated Genomics Outcome Scale Short Form, the validated Genetic Counseling Satisfaction Scale, and original questions. Survey topics included pre-test knowledge of the possibility of discovering PHR through testing, satisfaction with pre-test education that addresses potential risks, perceived severity of PHR, empowerment by and understanding of information, anxiety levels related to their PHR, perceived genetic counseling support, and satisfaction with telehealth. A total of 416 completed surveys were analyzed using descriptive statistics, and linear and logistic regressions. The majority of participants were satisfied or extremely satisfied with pre-test education (n = 328; 78.8%) and telehealth (n = 329; 79.1%). However, more participants who were aware of the possibility of identifying PHR through ECS prior to testing were satisfied with pre-test education compared to those who were not aware. Additionally, a lack of prior awareness of PHR was associated with lower empowerment scores (p = .004). Those who were highly satisfied with genetic counseling were more likely to feel empowered and understand the information presented (p = .001). The majority of individuals used their PHR information following their results appointment (n = 391; 94.0%). The results of this study suggest that receiving PHR information was useful and was positively influenced by both pre-test education and the genetic counseling process.

Interest in and uptake of genetic counseling for preconception carrier screening when offered to predominantly white reproductive-age persons seeking gynecologic care at a single U.S. academic medical center.

The objective of this study was to assess the level of interest in preconception carrier screening among reproductive-aged persons presenting for gynecologic care and to identify demographic factors predictive of pursuing screening. Patients aged 18-40 who were presenting for gynecologic care at a single U.S. academic medical center were provided with information about current options for preconception carrier screening and were offered genetic counseling referral with the possibility to undergo screening. Outcomes of interest were desire for genetic counseling referral and attendance at genetic counseling visit. Statistical analyses were performed as appropriate using R version 3.6.1 with variables significant at 0.1 included in a multivariable logistic regression. Of 193 participants, 79 (41%) desired genetic counseling referral. Participants aged 25-34 (OR 3.39, 95% CI 1.47-8.10) and nulliparas (OR 2.69, 95% CI 1.23-6.03) were more likely to desire referral. Thirty-five participants (44.3% of those who desired referral) attended a visit with genetic counseling. Having an advanced degree (OR 3.27, 95% CI 1.06-10.4) was associated with visit attendance. Thirteen participants underwent screening, and five were found to be a carrier of at least one X-linked or autosomal recessive condition. Surprisingly, presenting for a gynecologic visit directly related to planning a pregnancy was not associated with increased interest in preconception carrier screening. Nulliparas and those aged 25-34 likely expressed greater interest in referral due to high potential for future childbearing in these groups. The increased level of visit attendance in participants with advanced degrees is likely confounded by the high level of health literacy and financial resources in this group.

Reasons affecting the uptake of reproductive genetic carrier screening among nonpregnant reproductive-aged women in Flanders (Belgium).

Reproductive genetic carrier screening (RGCS) allows to identify couples who have an increased likelihood of conceiving a child affected with an autosomal recessive or X-linked monogenic condition. Multiple studies have reported on a wide and fragmented set of reasons to accept or decline RGCS. Only a few studies have been performed to assess the uptake of RGCS. Nonpregnant women visiting their gynecologist were invited to complete a questionnaire assessing perceived susceptibility, the acceptability of offering RGCS, attitudes, the intention to participate in RGCS, reasons to accept or decline RGCS, and sociodemographic characteristics. Women who showed the intention to have RGCS were asked to consider a free RGCS offer. Most women (n = 127) were between 25 and 34 years old (60%), in a relationship (91%), and wanted to have children (65%). Study participants had positive attitudes towards RGCS and the intention to consider RGCS in the future. Reasons to accept RGCS were being able to share genetic information with children or relatives (n = 104/127, 82%), to prevent the birth of a child affected with a hereditary condition (n = 103/127, 81%), and/or to know the chance of conceiving a child with a hereditary condition (n = 102/127, 80%). Reasons for declining RGCS were the possible concerns that could arise when receiving test results (n = 27/127, 21%), having no family history of hereditary disorders (n = 19/127, 15%), and not wanting to take action based on test results (n = 13/127, 10%). Among test intenders that met the inclusion criteria, 53% decided to participate in RGCS together with their male reproductive partner. More in-depth research on the decision-making process behind the choice to accept or decline an RGCS offer would be highly valuable to make sure couples are making informed reproductive choices.

Experiences of adolescents and their parents after receiving adolescents' genomic screening results.

There has been considerable debate over whether adolescents should have the opportunity to learn genetic information about adult-onset disease risk and carrier status without a clinical indication. Adolescents face increasing opportunities to learn more about such genetic risks through the return of secondary findings from clinical genomic testing, direct-to-consumer genetic testing, and research opportunities. However, little is known about the perspectives of adolescents who have received genomic screening results. We conducted separate qualitative interviews with 15 adolescents and their parents who enrolled in a research protocol where they decided which genomic screening results to receive for the adolescent for up to 32 conditions informed by 84 genes. The goal of these interviews was to explore the impact of adolescents learning genomic results without a clinical indication for screening. Of the participating dyads, four received positive results for a pathogenic/likely pathogenic (P/LP) variant for an autosomal dominant (AD) condition, five received carrier results for a heterozygous P/LP variant for an autosomal recessive (AR) condition, and six received negative results. An interpretive descriptive qualitative approach was used. Interview transcripts were coded using a guide developed by the study team based on themes that emerged from the interviews. Degree of recall and description of results, actionability, and emotional responses differed according to the types of results received. However, all participants were satisfied with their decision to learn results, and most did not report any lasting psychological harms. Participants adapted to genomic information about themselves, even after learning about unexpected increased risk for future health problems. Our findings support the position that, whenever possible, perspectives and wishes of adolescents should be strongly considered and respected in the decision-making process regarding genetic testing.

Genetic testing for pheochromocytoma and paraganglioma: SDHx carriers' experiences.

Pheochromocytoma and paraganglioma are frequently hereditary tumors commonly associated with succinate dehydrogenase (SDHx) pathogenic variants (PV). Genetic testing is recommended to relatives of patients carrying SDHx PV. This study aims to explore the experiences associated with genetic testing for this hereditary condition. Semi-structured interviews with 38 SDHx PV (tumor-affected and non-affected) carriers were transcribed and content-analyzed. Four ways of living with this genetic alteration emerged from the interviews: 'living as if not knowing', 'preventing others from going through this', 'feeling privileged', and 'still suffering'. Within each, negative, neutral, and positive reactions to the actual test result emerged initially, in addition to blame and guilt. Recognition of the importance of the genetic test and of the follow-up occurred in all four, but views on fecundity were divided between having and not having children. Consideration for the four different meanings of carrying an SDHx PV can improve participants' experiences and clinical practice.

Comparison of methodologies to detect hemoglobinopathy carriers in a multi-ethnic sperm donor population.

An estimated 7% of the world's population are carriers for a hemoglobin disorder. Current guidelines recommend carrier screening by complete blood count, with follow-up hemoglobin electrophoresis or fractionation based on abnormal result or ethnicity. Advances in molecular genetic testing are thought to increase carrier detection. This study compares carrier screening methodologies in a multi-ethnic sperm donor population. A retrospective analysis was conducted using data from a US sperm bank. All men underwent carrier screening for hemoglobin disorders via complete blood count, hemoglobin fractionation, and molecular testing. Results were compared using counts and percentages. McNemar's exact test was used to examine differences in the marginal probabilities of screening methodologies. Of the 438 tested, 25 (5.7%) were identified as carriers of at least one hemoglobin disorder by molecular testing. Seventeen (68%) of those carriers were missed by recommended methods. No identified carriers were detected by recommended methods but missed by molecular testing. The difference between these discordant pairs was significant (p-value < 0.001). The majority (44%) of carriers were mixed ethnicity, followed by 36% White. Results indicate that molecular screening methodologies have a greater ability to detect carriers of hemoglobin disorders compared to currently recommended methods in a multi-ethnic population.

Comparison of pan-ethnic and ethnic-based carrier screening panels for individuals of Ashkenazi Jewish descent.

The intent of carrier screening is to identify individuals at risk for having a child with a genetic disorder. American College of Medical Genetics and Genomics (ACMG) guidelines currently recommend that individuals of Ashkenazi Jewish (AJ) descent be screened for carrier status for nine disorders. However, a joint statement from five professional organizations acknowledges benefits of expanded carrier screening and this is becoming common practice. To better understand the impact of expanded carrier screening for the AJ population, we performed a retrospective analysis comparing detection rates for AJ individuals screened by two targeted panels: a pan-ethnic panel comprising 87 disorders and an AJ panel comprising an 18-disorder subset of the pan-ethnic panel. We also extrapolated the detection rates for the 18 AJ disorders from the pan-ethnic panel data and for the nine ACMG-recommended disorders using data from both panels. We found that with the pan-ethnic panel 431/1150 (37.5%) individuals were carriers of at least one disorder, compared to 319/1248 (25.6%) individuals with the AJ panel. If the pan-ethnic panel cohort were tested in the AJ panel or for the nine ACMG-recommended disorders, the detection rates would have been 280/1150 (24.3%) and 207/1150 (18.0%) respectively. Therefore, the pan-ethnic expanded carrier screening panel of 87 disorders increased the carrier detection rate in AJ individuals by approximately 50% and 100%, respectively, compared with a panel of 18 disorders considered relevant to the AJ population and the ACMG-recommended disorders. Twenty disorders accounted for the difference in carrier detection rates between the pan-ethnic and AJ panels. Of these, three were among the 10 most commonly identified disorders. Our findings reinforce published data that targeted AJ panels are less effective than a pan-ethnic panel in carrier detection among AJ individuals and provide metrics to address the impact of expanded carrier screening in this population.

Practices in synagogues regarding Jewish genetic disease education.

Approximately one in three Ashkenazi Jews are carriers for an autosomal recessive Jewish genetic disease (JGD). However, studies indicate that most Jews are uneducated on this topic and obstetricians do not routinely offer carrier screening to Jewish patients. Both the Reform and Conservative movements of Judaism call for JGD education to take place within the synagogue; however, little is known about the extent of this education occurring today. An online survey was created for Reform and Conservative rabbis to assess the types of JGD education taking place within the synagogue. Additionally, the survey included questions to assess JGD knowledge and possible factors that could predict counseling activity and knowledge level. Of the 94 participants, 91% had provided education about JGDs to congregants, with 98.8% providing this education during premarital counseling sessions. For most respondents, explaining recessive inheritance pattern and carrier screening was the extent of the discussion. Additionally, the majority of rabbis scored below 50% on the knowledge portion of the survey, with an average score of 1.9/4. There were no statistically significant differences between JGD education in Reform vs. Conservative synagogues, and there were no statistically significant predictors of knowledge score or JGD education frequency. In conclusion, while the number of rabbis discussing this topic is encouraging, discussion topics were found to be limited and their knowledge of JGDs was found to be poor.

Genetic testing costs and compliance with clinical best practices.

We sought to determine the costs of genetic testing and compliance with published guidelines and clinical best practices at our institution. A cost analysis was performed comparing the costs of ordered tests to the cost of the recommended testing. This was an approved quality improvement project at a tertiary teaching hospital in California. We identified charts associated with the genetic testing billing codes for common genetic tests through our contracted laboratory (cystic fibrosis genotyping, Breast cancer susceptibility gene (BRCA 1&2), Methylenetetrahydrofolate reductase (MTHFR), factor V Leiden (FVL), prothrombin gene pathogenic variant, alpha-thalassemia, hemochromatosis, and cell-free fetal DNA). Charts were reviewed retrospectively by a licensed, certified genetic counselor to assess the compliance with published clinical practice guidelines identified on GeneReviews and the American College of Obstetricians and Gynecologists (ACOG). Tests were classified as: appropriate, misordered/not indicated, misordered/false reassurance, and misordered/inadequate. We performed a cost analysis for the recommended test changes. We reviewed 114 charts over a three-month period. Forty-four (38.6%) of the tests were misordered based on published clinical practice guidelines: 24 (21%) were misordered/not indicated, 8 (7%) were misordered/false reassurance, and 12 (10.5%) were misordered/inadequate. Costs of ordered testing ($75,177) were compared to recommended testing after review ($54,265), with a total cost savings of $20,912. In clinical practice, over one-third of genetic tests reviewed were misordered. As these tests are a small fraction of all genetic tests at our institution, future studies should broaden the scope of testing evaluated to understand the magnitude of this problem and potential cost savings. Genetic counselor review and involvement in genetic test ordering can decrease inappropriate healthcare expenditures and improve patient care.

The incidence and carrier frequency of Tay-Sachs disease in the French-Canadian population of Quebec based on retrospective data from 24 years, 1992-2015.

Tay-Sachs disease (TSD) is a hereditary neurodegenerative condition inherited through an autosomal recessive pattern. The incidence and carrier frequency of infantile TSD were found to be increased among French Canadians in specific areas of the province of Quebec or calculated from New England populations with French-Canadian heritage. No accurate infantile TSD carrier frequency for the whole French-Canadian population in Quebec has been published. In this study, we estimate the incidence and carrier frequency of infantile TSD in the Quebec French-Canadian population. The number of TSD cases was ascertained during the 1992-2015 period, as well as the number of births to mothers whose language of use is French. Seven cases of TSD have been diagnosed in Quebec during the period of ascertainment. This corresponds to an incidence of 1/218,144, which in turn corresponds to a carrier frequency of 1/234. In the same 24-year period, there are two French-Canadian couples who had a fetus prenatally diagnosed with TSD. If these cases are included, the incidence of TSD in the French-Canadian population of Quebec is 1/169,668 and the carrier frequency 1/206. These findings can be used for genetic counseling and policy decisions regarding carrier screening for TSD in populations of French-Canadian descent.

Social and cultural influences on genetic screening programme acceptability: A mixed-methods study of the views of adults, carriers, and family members living with thalassemia in the UK.

As population-level carrier screening panels for reprogenetic information emerge globally, conditions to be included, and the timing of implementation is widely debated. Thalassemia is the only condition for which population-based prenatal carrier screening is offered in the UK. However, little is known about the views and experiences of the UK thalassemia-affected community toward this screening or other forms of genetic screening for thalassemia (newborn, preconception), despite the range of direct consequences of screening programmes for this group. Using a mixed-methods integrative analysis (qualitative interviews n = 20 and quantitative survey n = 80), this study outlines the experiences and attitudes of adults with thalassemia, their family members, and screen-identified thalassemia carriers toward preconception, prenatal, and newborn screening for thalassemia. The majority of participants described thalassemia as a burdensome condition with a range of negative impacts, which contributed to their strong support for screening in all its potential formats. However, the data also highlight the challenges of each screening mode for this group, reflected in the high level of value conflict in participants' accounts and decisions. Cultural, social, and (to a lesser extent) religious factors were found to mitigate against the advantages of early screens, particularly within faith communities. Social stigma emerged as key to this process, informing the way that thalassemia severity was not only perceived, but also experienced by affected adults, which ultimately influenced screening uptake and outcomes. These findings suggest that cultural and social sensitivity is as important as the mode of screening delivery itself, if the iatrogenic and unintended harms of screening-particularly the social/psychological burden of value conflict-are to be adequately addressed and minimized.

Giving adolescents a voice: the types of genetic information adolescents choose to learn and why.

PURPOSE: The American College of Medical Genetics and Genomics supports parents' opting in or out of secondary analysis of 59 genes when their child has clinical exome/genome sequencing. We explored the reasons adolescents choose to learn certain types of results and the reasons they want to involve or not involve parents in decision-making. METHODS: Adolescents recruited without clinical indication were offered independent, followed by joint choices with a parent to learn genomic results. After making independent choices, adolescent/parent dyads were interviewed to explore the reasons for their choices. Interviews were audio-recorded and transcribed. The constant comparative method was used to analyze 64 purposefully selected transcripts that included 31 from adolescents who excluded some or all potential results. RESULTS: Three major themes informed adolescents' choices: (1) actionability of information, (2) knowledge seeking, and (3) psychological impact. Of adolescents who independently excluded some conditions (n=31), 58% changed their initial choices during the joint interview due to parental influence or improved understanding. Nearly all adolescents (98%) wanted to be involved in the decision-making process, and 53% wanted to make choices independently. CONCLUSIONS: Our findings contribute empirical evidence to support the refinement of professional guidelines for adolescents' engagement and preferences in genetic testing decisions.