This document of the European Society of Human Genetics contains recommendations regarding responsible implementation of expanded carrier screening. Carrier screening is defined here as the detection of carrier status of recessive diseases in couples or persons who do not have an a priori increased risk of being a carrier based on their or their partners' personal or family history. Expanded carrier screening offers carrier screening for multiple autosomal and X-linked recessive disorders, facilitated by new genetic testing technologies, and allows testing of individuals regardless of ancestry or geographic origin. Carrier screening aims to identify couples who have an increased risk of having an affected child in order to facilitate informed reproductive decision making. In previous decades, carrier screening was typically performed for one or few relatively common recessive disorders associated with significant morbidity, reduced life-expectancy and often because of a considerable higher carrier frequency in a specific population for certain diseases. New genetic testing technologies enable the expansion of screening to multiple conditions, genes or sequence variants. Expanded carrier screening panels that have been introduced to date have been advertised and offered to health care professionals and the public on a commercial basis. This document discusses the challenges that expanded carrier screening might pose in the context of the lessons learnt from decades of population-based carrier screening and in the context of existing screening criteria. It aims to contribute to the public and professional discussion and to arrive at better clinical and laboratory practice guidelines.

BackgroundCarrier screening is generally performed with the aim of identifying healthy couples at risk of having a child affected with a monogenic disorder to provide them with reproductive options. Expanded carrier screening (ECS), which provides the opportunity for multiple conditions to be screened in one test, offers a more cost-effective and comprehensive option than screening for single disorders. However, implementation of ECS at a population level would have implications for genetic counseling practice.MethodsWe conducted semi-structured interviews with sixteen European clinical and molecular geneticists with expertise in carrier screening to explore their views on the implementation of ECS in the clinical setting.ResultsUsing inductive content analysis, we identified content categories relevant to the pre- and post-test settings. Participants believed ECS would ideally be targeted at couples before pregnancy. There was some disagreement regarding the acceptability of performing ECS in individuals, with several participants actively opposing individual-based screening. In addition, participants discussed the importance of ensuring informed and voluntary participation in ECS, recommending measures to minimize external pressure on prospective parents to undergo testing. A need for adequate counseling to foster informed, autonomous reproductive decision-making and provide support for couples found to be at risk was emphasized.ConclusionsPractical challenges in optimizing pre-test education and post-test counseling should not be underestimated and they should be carefully addressed before implementing ECS in the clinical setting.

Although a limited ECS offer is practical, it also raises concerns over equality in access to screening. A comprehensive risk-benefit analysis is needed to determine the desirability of systematic population-wide ECS.

Aims: To explore the views of the Belgian public on various topics surrounding genetics and genetic testing (GT). Materials and Methods: A written questionnaire was administered to visitors of the annual cartoon festival in Knokke-Heist, Belgium, during the summer of 2014. The main theme of the festival was challenges and progress in human genetics and it was attended by more than 100,000 visitors. Results: The survey was completed by 1182 respondents, resulting in a demographically diverse sample with a mean age of 48.5 years. Our respondents expressed moderate interest in predictive GT, with 39.1% willing to learn about their predisposition to diseases through GT and 49.5% indicating interest in getting tested exclusively for treatable/preventable diseases. We observed higher interest in GT for reproductive purposes, such as preconception screening for recessive disorders (53.8%) and prenatal GT (60.7%). A substantial minority (46.4%) of the respondents were worried that GT could further stigmatize people with disabilities, while 39.7% believed that carrier screening for recessive diseases would lead to an inferior image of people affected by them. Conclusion: Paying due attention to the attitudes, beliefs, and concerns of the general public is important to ensure ethically sound and socially acceptable implementation of new genetic technologies.

Participation in healthcare decision-making is considered to be an important right of minors, and is highlighted in both international legislation and public policies. However, despite the legal recognition of children's rights to participation, and also the benefits that children experience by their involvement, there is evidence that legislation is not always translated into healthcare practice. There are a number of factors that may impact on the ability of the child to be involved in decisions regarding their medical care. Some of these factors relate to the child, including their capacity to be actively involved in these decisions. Others relate to the family situation, sociocultural context, or the underlying beliefs and practices of the healthcare provider involved. In spite of these challenges to including children in decisions regarding their clinical care, we argue that it is an important factor in their treatment. The extent to which children should participate in this process should be determined on a case-by-case basis, taking all of the potential barriers into account.

BACKGROUND Through carrier screening, prospective parents can acquire information about whether they have an increased risk of conceiving a child affected with an autosomal recessive or X-linked condition. Within the last decade, advances in genomic technologies have facilitated a shift from condition-directed carrier screening to expanded carrier screening (ECS). Following the introduction of ECS, several studies have been performed to gauge the interest in this new technology among individuals and couples in the general population. OBJECTIVE AND RATIONALE The aim of this systematic review was to synthesize evidence from empirical studies that assess the interest in ECS among individuals and couples in the general population. As the availability and accessibility of ECS grow, more couples who are a priori not at risk based on their personal or family history will be presented with the choice to accept or decline such an offer. Their attitudes and beliefs, as well as the perceived usefulness of this screening modality, will likely determine whether ECS is to become a widespread reproductive genetic test. SEARCH METHODS Four databases (Pubmed, Web of Science, CINAHL, Cochrane Library) were systematically searched to identify English language studies performed between January 2009 and January 2019 using the following search terms: carrier screening, carrier testing, attitudes, intention, interest, views, opinions, perspectives and uptake. Studies were eligible for inclusion if they reported on intentions to undergo a (hypothetical) ECS test, uptake of an actual ECS offer or both. Two researchers performed a multistep selection process independently for validation purposes. OUTCOMES Twelve empirical studies performed between 2015 and 2019 were included for analysis. The studies originated from the USA (n = 6), the Netherlands (n = 3), Belgium (n = 1), Sweden (n = 1) and Australia (n = 1). The sample size of the studies varied from 80 to 1669. In the included studies, 32%–76% of respondents were interested in a (hypothetical) ECS test, while uptake rates for actual ECS offers ranged from 8% to 50%. The highest overall uptake was observed when ECS was offered to pregnant women (50%). By contrast, studies focusing on the preconception population reported lower overall uptake rates (8–34%) with the exception of one study where women were counseled preconception in preparation for IVF (68.7%). WIDER IMPLICATIONS Our findings suggest that there may be discrepancies between prospective parents’ reported intentions to undergo ECS and their actual uptake, particularly during the preconception period. As ECS is a new and relatively unknown test for most future parents, the awareness and comprehension within the general population could be rather limited. Adequate pre- and post-test counseling services should be made available to couples offered ECS to ensure informed reproductive decision-making, together with guidelines for primary health care professionals. Due to restricted nature of the samples and methods of the underlying primary studies, some of the reported results might not be transferable to a broader population. More research is needed to see if the observed trends also apply to a broader and more diverse population.

Since the introduction of out-of-hospital health-related genetic tests more than a decade ago, the landscape of genetic testing services has grown in complexity. Although initially most genetic tests for health purposes were offered as direct-to-consumer services, that is, without the mediation of a medical professional, currently many commercial providers require that their tests be ordered by a licensed physician. At the same time, some commercially developed health-related genetic tests are gaining support from the professional medical community and are finding their way into clinical practice. Therefore, we differentiated between three types of genetic testing offers: direct-to-consumer, physician-mediated, and clinic-based genetic testing. Expanded carrier screening tests for recessive disorders are currently available through all the three models of genetic testing. Herein, we review the present landscape of expanded carrier screening offers by highlighting the distinct issues associated with each of the three types of genetic testing.

Introduction: Carrier screening for recessive disorders is undertaken by prospective parents to inform their reproductive decisions. With the growing availability of affordable and comprehensive expanded carrier screening (ECS), it is expected that carrier screening will become a standard practice in the future. However, the impact of positive carrier screening results on the reproductive decisions of at-risk couples (ARCs) remains underexplored. Areas covered:We performed a systematic literature review to identify peer-reviewed publications describing reproductive decisions of ARCs. Our search identified 19 relevant publications spanning the period 1994 -2018. By synthesizing available evidence, we found that most ARCs chose to prevent the birth of an affected child and the decision to utilize preventive reproductive options was strongly influenced by the clinical nature of a disorder.However, there was also some heterogeneity in reproductive decisions within the same recessive disorders, suggesting that choices of ARCs can be influenced by factors other than the clinical nature of a disorder.Expert opinion: ECS is becoming increasingly common, which will result in the routine identification of many ARCs. Reproductive decision-making by ARCs is a complex and emotionally challenging process, highlighting the critical role of genetic counseling in the care for these potentially vulnerable patients.