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.

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access.

The objective of this study is to review ethical and clinical guidelines and position papers concerning the presymptomatic and predictive genetic testing of minors. The databases Medline, Philosopher's Index, Biological Abstracts, Web of Science and Google Scholar were searched using keywords relating to the presymptomatic and predictive testing of children. We also searched the websites of the national bioethics committees indexed on the websites of World Health Organization (WHO) and the German Reference Centre for Ethics in the Life Sciences, the websites of the Human Genetics Societies of various nations indexed on the website of the International Federation of Human Genetics Societies and related links and the national medical associations indexed on the website of the World Medical Association. We retrieved 27 different papers dealing with guidelines or position papers that fulfilled our search criteria. They encompassed the period 1991-2005 and originated from 31 different organizations. The main justification for presymptomatic and predictive genetic testing was the direct benefit to the minor through either medical intervention or preventive measures. If there were no urgent medical reasons, all guidelines recommend postponing testing until the child could consent to testing as a competent adolescent or as an adult. Ambiguity existed for childhood-onset disorders for which preventive or therapeutic measures are not available and for the timing of testing for childhood-onset disorders. Although the guidelines covering presymptomatic and predictive genetic testing of minors agree strongly that medical benefit is the main justification for testing, a lack of consensus remains in the case of childhood-onset disorders for which preventive or therapeutic measures are not available.

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This analysis indicates that future policy responses and recruitment practices should be attentive to a wide variety of concerns in order to promote both responsible and progressive research.

Since its origin, bioethics has attracted the collaboration of few social scientists, and social scientific methods of gathering empirical data have remained unfamiliar to ethicists. Recently, however, the clouded relations between the empirical and normative perspectives on bioethics appear to be changing. Three reasons explain why there was no easy and consistent input of empirical evidence in bioethics. Firstly, interdisciplinary dialogue runs the risk of communication problems and divergent objectives. Secondly, the social sciences were absent partners since the beginning of bioethics. Thirdly, the meta-ethical distinction between 'is' and 'ought' created a 'natural' border between the disciplines. Now, bioethics tends to accommodate more empirical research. Three hypotheses explain this emergence. Firstly, dissatisfaction with a foundationalist interpretation of applied ethics created a stimulus to incorporate empirical research in bioethics. Secondly, clinical ethicists became engaged in empirical research due to their strong integration in the medical setting. Thirdly, the rise of the evidence-based paradigm had an influence on the practice of bioethics. However, a problematic relationship cannot simply and easily evolve into a perfect interaction. A new and positive climate for empirical approaches has arisen, but the original difficulties have not disappeared.

Although NGS technologies are well-embedded in the clinical setting for identification of genetic causes of disease, guidelines issued by professional bodies are inconsistent regarding some aspects of reporting results. Most recommendations do not give detailed guidance about whether variants of uncertain significance (VUS) should be reported by laboratory personnel to clinicians, and give conflicting messages regarding whether unsolicited findings (UF) should be reported. There are also differences both in their recommendations regarding whether actively searching for secondary findings (SF) is appropriate, and in the extent to which they address the duty (or lack thereof) to reanalyse variants when new information arises. An interdisciplinary working group considered the current guidelines, their own experiences, and data from a recent qualitative study to develop a set of points to consider for laboratories reporting results from diagnostic NGS. These points to consider fall under six categories: (i) Testing approaches and technologies used, (ii) Approaches for VUS; (iii) Approaches for reporting UF, (iv) Approaches regarding SF; (v) Reanalysis of data & re-contact; and vi) Minors. While it is unclear whether uniformity in reporting across all laboratories is desirable, we hope these points to consider will be useful to diagnostic laboratories as they develop their processes for making decisions about reporting VUS and UF from NGS in the diagnostic context.

ESHG background document genetic testing and common disorders F Becker et al S10 European Journal of Human Genetics Knowledge of test Feasibility of screening procedures Suitable test or examination. Suitable test or examination. Test acceptable to the population. Entire screening procedure acceptable to the population. Case finding should be a continuing process and not 'once and for all' project. Screening should be a continuing process and should encompass all elements of screening procedures. Treatment for disease Interventions and follow-up Accepted treatment for patients with recognized disease. Interventions that have physical, psychological, and social net benefit available. Facilities for diagnosis and treatment available. Facilities for adequate surveillance, prevention, treatment, education, counselling, and social support available. Agreed on policy concerning whom to treat as patients. Consensus on accepted management for those with positive test results. Cost considerations Societal and health system issues Costs of case finding (including diagnosis and treatment of patients diagnosed) economically balanced in relation to possible expenditures on medical care as a whole. Costs should be balanced in economic, psychological, social, and medical terms and with health-care expenditures as a whole. Appropriate screening services accessible to the entire population, without adverse consequences for non-participants. Appropriate confidentiality procedures and antidiscrimination provisions for participants and non-participants. a Ethical, legal, and sociobehavioral issues are considered across all domains. Screening should be considered within a framework that recognizes fundamental human rights.