IntroductionNewborn screening (NBS) is among the most effective means of secondary prevention and has helped to shift the traditional paradigm of medicine from symptom-driven to pre-symptomatic diagnosis in phenotypically healthy individuals [1]. Concurrently, genomic sequencing is offered as a diagnostic component, to guide treatment decisions, to establish heritability, and for counseling of families with history of a genetic disease [2]. Also, for NBS, which is continuously expanded, genomic sequencing is expected to pave the next major expansion of this program [3]. A genomic NBS (gNBS) would allow for the detection of hundreds of target diseases undetectable with current NBS techniques [4, 5]. To provide information only about target diseases, a virtual panel would have to be carefully set with the help of bioinformatic filters. Such a panel would allow rapidly including additional diseases without extensive methodological effort, but at the same time increases the risk of potential harm if diseases, and gene variants are not carefully selected.Public health screening has, for a long time, been guided by the Wilson and Jungner screening principles [6]. However, they were not intended to be used for such selection decisions and are particularly insufficient to regulate a modern (g)NBS program because they lack measurability, a pediatric and genomic focus, and program management aspects [7]. Adapted screening criteria have been proposed by various groups with still limited impact on (inter)national NBS regulations [8,9,10,11,12]. Accordingly, the selection of target diseases for current NBS programs, and gNBS pilot studies, varies substantially [13,14,15], e.g., among seven gNBS pilot studies (237–889 target diseases), only 53 included diseases overlapped, mostly inherited metabolic conditions covered by current NBS programs [14].There is a need to develop revised screening criteria before genomic sequencing can be effectively introduced into NBS public health programs. To achieve this goal, this study aims at developing a multidimensional approach through integration of medical, ethical, legal, and social aspects (ELSA), input from patient representatives, and guidance on program-management [1, 7, 16].Materials and MethodsTo cover and integrate relevant gNBS expertise, an interdisciplinary panel was assembled as the research project group “NEW_LIVES: Genomic NEWborn Screening Programs – Legal Implications, Value, Ethics and Society” in October 2022 [17] including three pediatricians specialized in pediatric metabolic medicine with long-standing expertise in NBS research, three clinical geneticists with a research focus on genomic medicine and gNBS, four researchers and clinical practitioners in medical psychology, four researchers in medical ethics, two researchers in legal studies, and two representatives of large patient organizations. The interdisciplinary composition of the expert group, integrating ELSA, and the focus on selection criteria for a possible future gNBS as a public health program, in contrast to pilot studies, differed from previous studies.First, the expert group conducted extensive literature reviews, evaluated ELSA of gNBS [7, 14, 18,19,20,21], captured societal perspectives in a focus group study with parents, medical professionals, and patient representatives [22], and conducted two quantitative studies, the interim results of which informed the further steps of the study: a representative population-wide survey, and an online survey with parents. Based on these multidisciplinary results, the panel decided on a structure for potential screening criteria, consisting of four subcategories: (I) clinical, (II) diagnostic, (III) therapeutic, and (IV) program management criteria [7].In a second step, a process similar to the Nominal Group Technique, a structured group decision-making method which is widely used [23,24,25], was used to reach consensus gathering iterative feedback from all group members, and integrating it into the decision-making process (Fig. 1). The interdisciplinary discourse was moderated, and documented by an expert for medical ethics (KA). She also ensured that any group member was allowed to raise concerns, and add considerations at any time, prepared, and circulated detailed meeting minutes including all raised concerns, and measured consensus of all experts. The process started in February 2023, and involved:(1)Informed by a literature review [7], ethico-legal analyses [19,20,21], empirical studies [22], and ClinGen Gene Curation Working Group (ClinGen) definitions [26], initial suggestions for medical aspects and ELSA were discussed in a subgroup of the panel with at least one representative per discipline.(2)The expert panel then established a preliminary list of screening criteria in shared online documents, and refined and continuously revised it during monthly hybrid group discussion meetings, based on structured feedback. This also included feedback during an Advisory Board meeting (January 2024, online) and international conference (Heidelberg, March 2024) from interdisciplinary national and international experts on NBS, gNBS, and genome sequencing, law, medical ethics, and patients’ perspectives.(3)Following additional rounds of group discussions on each of the four subcategories of criteria implementing final adjustments to their wording, the presented list of 18 screening criteria emerged, and was approved by all expert group members during a group meeting on August 05, 2024.Fig. 1: Working process for developing screening criteria for a future genomic newborn screening program.After initial suggestions regarding ethical, legal, social and medical considerations for potential screening criteria, a process similar to the Nominal Group Technique was applied to reach consensus decision, gathering iterative feedback from all experts, including international input from the advisory board and an international conference. The consented screening criteria are assigned to four subcategories: Clinical, Diagnostic, Therapeutic and Program Management Criteria. gNBS: genomic newborn screening. Figure was created with draw.io (https://drawio-app.com/, accessed on February 03, 2025).Full size imageResultsThe above-described methodology resulted in a multi-dimensional framework for a gNBS program consisting of 18 screening criteria (Table 1) assigned to two overarching categories and four subcategories:(A)Criteria that enable transparent disease selection:I.Four clinical criteria,II.Four diagnostic criteria, andIII.Three therapeutic-interventional criteria(B)Criteria to establish, manage, and further develop the gNBS program:IV.Seven program management criteria.Table 1 Criteria for a genomic newborn screening program (by the project group NEW_LIVES).Full size tableA target disease qualifies for inclusion in a population-wide gNBS program if all screening criteria in subcategories I–III are met, while any (g)NBS program should meet all seven program management criteria (subcategory IV) if established on a population-wide level.I. Clinical criteria (Characteristics of the target disease)(1)The gene-disease association of the target disease is “definitive” or “strong” according to the ClinGen classification.Evidence for the causal relationship between a gene and a disease should have been repeatedly demonstrated in both research and clinical diagnostics (“definitive”) or reported independently in ≥ 2 studies (“strong”). The expert panel recommends the use of a Gene-Disease Validity Classification Information, such as curated by ClinGen [27]. For gene-disease associations not covered by ClinGen, the same standards as in ClinGen should apply.(2)The penetrance of variants associated with the target disease is at least 80% for the corresponding gene.Only target diseases with high penetrance based on moderate to substantial evidence according to ClinGen [28] should be considered. For genetic diseases with multiple symptoms, penetrance refers to the clinically relevant main symptom. For target diseases not covered by ClinGen, the same standards as in ClinGen should apply. Target diseases with a penetrance of at least 80% would be, e.g., Nephropathic cystinosis (OMIM #606272) or Retinoblastoma (OMIM #614041).(3)The target disease is severe. This means that if left untreated, it results(a)in premature death, or(b)in major morbidity and a significantly impaired quality of life, or(c)in modest morbidity with a significantly impaired physical or cognitive development.For the assessment of the severity, the ClinGen classification system or a comparable database can be used.The expert panel has decided not to exclusively refer to the ClinGen classification as it leaves considerable room for interpretation. Diseases with “modest morbidity”, such as moderate intellectual disability, may not generally meet the definition of a severe disease, but are considered severe if associated with significant impairment of physical or cognitive development.(4)The average age of onset of the target disease is < 7 years of age.To avoid waiting periods until disease-onset and as applicable for most current NBS programs’ target diseases, only diseases with an average age of onset in early childhood should be included. The specific age limit of under seven years was chosen because children can give assent or dissent to genetic testing themselves from this age onwards. As genetic diseases usually have a wide range of age of onset, the average should be considered to trade-off between the benefit for children with earlier onset and avoidance of “patients in waiting” [29]. This is particularly important as any inclusion of a disease into NBS will lead to expansion of the known clinical phenotype, especially towards attenuated phenotypes, which are likely to shift the age of onset to a later timepoint [1].II. Diagnostic criteria (Requirements of the test)(5)A gNBS has proven advantages compared to the established diagnostic methods for the target disease. This means the target disease (1) cannot be detected by analytic methods of current NBS, but (2) can be detected by gNBS (a) more reliably (i.e., with higher sensitivity or specificity) or (b) at an earlier timepoint than with established methods of routine diagnostics.A population-wide gNBS is only justified if identified patients have an additional benefit compared to identification by current NBS of asymptomatic newborns or established diagnostic methods used for symptomatic individuals. Consequently, gNBS is not intended to replace current NBS but to be added for diseases that cannot be identified by current screening methods (#5 (1)) if the described advantages (#5 (2)) exist.(6)The target disease can be clearly identified by molecular genetics using genome sequencing. The technical quality parameters of the test correspond to those of accredited diagnostic laboratories. The gene variants to be reported are detected with an analytical-diagnostic sensitivity and specificity of almost 100%.The quality parameters of the test must meet the highest diagnostic standards and (likely) pathogenic variants must be detected. However, incomplete clinical sensitivity, caused by a high proportion of variants of uncertain significance (VUS), some of which may later be classified as pathogenic, should not be considered a general exclusion criterion for a target disease: if not all affected individuals receive a genetic diagnosis, those with a (likely) pathogenic variant in this gene would still benefit from reporting the findings. Genome sequencing can be used to identify single nucleotide variants, small rearrangements, and copy number variations, while, e.g., methylation defects cannot be identified with genome-sequencing methods commonly used today. This must be considered when selecting target diseases and adapted to new technologies.(7)Only “likely pathogenic” and “pathogenic” variants (ACMG classification) are reported. Carrier status and VUS are not reported.The American College of Medical Genetics and Genomics’ (ACMG) criteria for interpretation of sequence variants recommend five categories for classifying the probability that the variant is disease causing: pathogenic, likely pathogenic, uncertain significance (VUS), likely benign, and benign [30]. Information on symptoms and family history is required for classification, which is not available in the screening context. Therefore, and to achieve the highest possible specificity, only variants of the first two categories should be reported. Autosomal recessive heterozygous variants not relevant for the newborn’s health should not be reported. In X-linked inheritance, hemizygous males (karyotype 46, XY) are affected by the disease. Heterozygous females (46, XX) are usually less severely affected or unaffected; exceptions exist. Therefore, (likely) pathogenic variants in target diseases with X-linked inheritance are usually only reported in males.(8)The suspected diagnosis from gNBS is confirmed by (1) a molecular genetic test from an independently obtained sample (e.g. new blood sample) or (2) an established non-genetic diagnostic test (e.g. biochemical, enzymatic, image morphological, histological, electrophysiological).Screening tests differ from diagnostic tests. They identify individuals at risk for the identified condition, preferably during the preclinical stage of the disease. Thus, positive screening tests always require a careful and reliable confirmatory strategy, particularly, as in rare diseases false positive results are relatively frequent. For current NBS, biochemical and targeted genetic tests are used for confirmation [31]. Target diseases included in gNBS programs equally require a predefined pathway of suitable confirmatory tests. Whenever possible, confirmation diagnostics should include non-genetic functional biomarkers. If these are unavailable, confirmation should be based on a secondary genetic analysis with an alternative molecular genetic test in a new sample to exclude sample mix-up. A careful evaluation of the newborn’s phenotype and family history should be used to complete the confirmatory pathway. If the confirmatory diagnostics are based on a second genetic test, the biallelic phasing of the variants should be confirmed in autosomal recessive inheritance. If there are medically equivalent ways of confirmatory diagnostics, the one with the least discomfort for the child should be chosen.III. Therapeutic-interventional criteria (Prerequisites of the intervention)(9)A therapeutic intervention is established and available that demonstrably has a beneficial effect on the course of the target disease, which means that it prevents, alleviates, or delays the onset of disease-specific signs and symptoms. If this requires recurrent monitoring, interventions in the form of regular surveillance examinations are also established and available.Other possible benefits, such as non-medical actionability, secondary benefits to parents, siblings, or society, family planning implications, avoidance of a “diagnostic odyssey”, or just the wish to know, are not considered sufficient to justify the inclusion of a target disease in a population-wide NBS or gNBS.An ongoing clinical trial would not suffice to consider an intervention as “established”.“Available” means that all screened individuals have equal access to treatment and specialized teams offering monitoring and treatment. If gNBS also included diseases that did not require therapeutic intervention from the time of diagnosis but recurrent surveillance, e.g., RB1-related retinoblastoma, serial examinations necessary for regular surveillance as well as therapeutic interventions in the event of disease development would have to be established and available.(10)Pre- or early symptomatic start of intervention after identification of the target disease through gNBS is feasible and has a proven health benefit compared to starting the intervention after diagnosis by established methods of routine diagnostics.If pre- or early symptomatic initiation of therapy did not provide a health benefit, post-symptomatic targeted routine diagnostics would be sufficient and the candidate disease would not qualify for inclusion as target disease in gNBS. Since genome sequencing is frequently performed at the appearance of first symptoms and even ultra-rapid genome sequencing is increasingly available for critically ill children [32], the sole prevention of a “diagnostic odyssey” does not justify the inclusion into gNBS.(11)The benefit of the intervention clearly outweighs its risks and burdens for the child. The risk is low or moderate, comparable to a classification of the intervention risk of ≥ 2 (“low risk”; “moderately acceptable risk”) according to ClinGen. The assessment of benefits, risks and burdens considers the effects of the intervention on the child’s quality of life.The known risk and burden of therapeutic interventions or surveillance examinations should be outweighed by their potential benefit. Since the assessment of risks and benefits includes normative components, patient representatives should be involved in the process alongside medical and medical-ethics experts. Priority should always be given to the quality of life of the affected child because the burden and risk of an intervention as classified in ClinGen [33] may not (always) correspond to the perception of those affected [34].IV. Program management criteria (Structure of the program)Any NBS, including a gNBS, should be regarded as a public health measure. To offer guidance for the process of establishing, evaluating, and maintaining a (g)NBS program, seven criteria for program management have been defined (##12–18; Table 1).Equal access (#12), an important ethical requirement of any public health program, comprises guarantee of cost coverage for screening, confirmatory diagnostics, and consecutive interventions and care. Current NBS programs generally provide equal access to all newborns in the target region, and enable a very high participation rate, e.g., about 99.9% in Germany [35]. In contrast, cost coverage for recommended therapies is still incomplete, e.g., special diets are not regularly paid for by health insurances [36]. Nevertheless, achieving the greatest possible equality, including full-cost coverage of recommended follow-up care, should be the aim of any (g)NBS program.An additional challenge for equality are minorities for whom only limited population-specific genetic data might be available for genomic analysis. Since precise knowledge of the genetic variants in the screened population is an essential condition for the success of a gNBS, it seems sensible to include underrepresented populations in registry studies in order to achieve equitable representation.While equality of access (#12) implies that every newborn’s guardians are offered gNBS, participation needs to remain voluntary (##13–14). Although written informed consent (IC) is not uniformly required across all NBS programs worldwide [37], it should be mandatory for gNBS as for any genetic diagnostic test. Since gNBS is a complex topic, there is a balance to be achieved between information overload and insufficient information (#14). Withdrawal from gNBS is possible at any time (#14f) with the exception that a positive gNBS result, once obtained, will be communicated in the interest of the child.To make gNBS as minimally invasive for the child as possible, the same dried blood spot sample should be used for NBS and gNBS, utilizing the established system of filter paper cards. Sample collection, transport, and analysis (#15), confirmation and communication of test results, and the initiation of recommended interventions (#16) should follow clearly defined guidelines including exact procedures for each target disease. It is essential for a gNBS program that precise information about the procedure following a positive result, including specific contact persons, is provided to families directly after a positive screening report.The use of data, and samples from gNBS requires strict adherence to data protection laws (#17). Samples, and data from gNBS, as well as clinical follow-up data are of great value for program evaluation, and quality assurance (#17a–d), but also for adjustment, and improvement of the program. In addition, they might contribute to research on genetic diseases, potentially resulting in new or improved treatment, and to individual benefits. Since genetic data is considered particularly sensitive, it requires special protection. Therefore, the expert panel recommends that such secondary use of data should only be made possible either with separate written IC or where legally permitted (#17e), in both cases with additional safeguards (#17f), in compliance with applicable law and regularly updated to reflect changing legal requirements.A gNBS should be organized as an integrated and learning public health program with central coordination, data-driven evaluation of quality, safety and acceptability, and re-evaluation of target diseases, including case definitions and recommended interventions (#18).DiscussionThe proposed screening criteria aim to establish a transparent multi-dimensional framework for the future development of gNBS programs as the expected next major NBS expansion.Towards harmonization of selection criteria for target diseasesCurrently, the selection of target diseases for international NBS programs and gNBS pilot studies varies considerably [13,14,15]. Several factors may contribute to this heterogeneity, including country-specific priorities, different medical backgrounds of pilot project investigators, and differently weighted screening criteria [4, 5]. The overarching question is how screening criteria for a gNBS public health program should be designed to lead to sufficient agreement and international harmonization. This is particularly important as, without consensus, there is a high risk of increasing confusion and variability in target disease-lists. Our approach differs from many pilot studies in three aspects: first, we focus on the definition of selection criteria for target diseases before compiling a target disease list, second, we defined the criteria in view of a possible future gNBS public health program in contrast to a pilot study, and included aspects of program management, and third, we reached consensus based on an interdisciplinary expert group. Therefore, we believe that our proposed selection criteria provide a good basis for international harmonization.A balanced approach to selecting screening criteriaThe proposed screening criteria are designed conservatively to avoid uncertainty and to improve acceptability by the following three measures:(1)Each of the criteria must be fulfilled, and all criteria are treated equally. While alternative approaches like prioritized criteria or a scoring system would be conceivable [5, 38], this weighing would lack evidence.(2)The screening criteria focus on the benefit and best interests of the newborn. Potential benefits to parents or siblings alone are insufficient for the inclusion as a target disease.(3)The criteria themselves are designed to be conservative and stringent, e.g., penetrance must be above 80% or the disease must occur on average (and not at the earliest) before the age of seven years.There are (a) medical, (b) ethical, (c) legal, and (d) societal and psychological reasons supporting the conservative approach.(a) NBS is a predictive test for individuals who are considered healthy and have a cumulatively low risk of being affected by the target diseases. There are no symptoms to guide the interpretation of test results. For parents, the primary expectation of NBS is not the diagnosis of a condition, but rather the confirmation of their child’s healthiness. Therefore, it is crucial that conditions are detected with the highest possible certainty, that a reported condition will manifest with high likelihood, and that an effective intervention can be provided. Some aspects, such as penetrance, are particularly prone to misestimation due to selection bias or insufficient data, which is why consideration of the level of evidence was included. Uncertainty may lead to overdiagnosis and overtreatment as well as anxiety, and program rejection.(b) The proposed conservative approach is supported by the four core principles of biomedical ethics: nonmaleficence, beneficence, justice, and respect for autonomy [39]. Stringent requirements for, e.g., gene-disease association (#1), penetrance (#2), variant pathogenicity (#7), and confirmation of suspected diagnoses (#8), aim to prevent harm for newborns, and their parents. The prevention of severe genetic diseases as the primary benefit of gNBS can only be guaranteed – and guaranteed justly, so that risks and benefits to all screening participants are considered – if stringent requirements for sensitivity and specificity apply (#6), and recommended interventions are available (#9) as well as equally accessible (#12). The stringent requirements for the IC process (##13–14, 17) are ethically justified by the principle of respect for autonomy.(c) The conservative approach can furthermore be supported by legal arguments pertaining to Germany, e.g. the specifications for the content of the IC session (#14) largely reflect the requirements of § 9 para 2 no 1–6 German Genetic Diagnostics Act. Similarly, the requirement of an established and available therapeutic intervention (#9) is consistent with the provisions of § 16 para 1 German Genetic Diagnostics Act. Furthermore, the requirement in #11 – benefits of the intervention must clearly outweigh the risks and burdens for the child – ensures compliance with the fundamental principle of the best interests of the child.(d) The proposed stringent requirements are intended to promote broad societal acceptance (#18d), which is considered crucial for sustainable implementation of the program, and broad participation. Previous empirical studies identified concerns regarding data protection and privacy [22, 40, 41] and about results without clear clinical implications [22, 41,42,43]. The potential for emotional distress, and psychological burden arising from the ambiguity of findings has also been emphasized [44], supporting a more cautious and restrictive approach also from a psychological perspective. Consistent with this, Australian stakeholders favored a cautious course [45]. While several studies have shown that parents express interest in a broad spectrum of information – even in the absence of actionable treatments –, there is nevertheless a stronger consensus in favor of disclosing findings related to conditions with specific therapeutic options [46,47,48].Proposed approach – Possible limitations and unresolved concernsThe proposed screening criteria focus on severe, early onset and treatable target diseases to reduce uncertainty and maximize the benefit for newborns. In contrast to this, parents and clinicians sometimes highlight genomic data’s utility for families even in the absence of medical utility for the child [15, 49]. In this context, certainty of prediction seems to be assigned higher priority than treatability [50], and benefits may be expected for “family planning and testing, the intrinsic value of information, and the ability to prepare for the future” [49]. Some gNBS pilot projects therefore offer a complementary opt-in for extended results [4, 15]. This would give parents more autonomy in deciding on the return of results. There are, however, also indications that parents have exaggerated expectations of gNBS and overestimate its potential benefits [49]. This should be considered when developing selection options and IC materials. In particular, a strict analogy between gNBS pilot projects with a more liberal approach and a population-wide gNBS program, as discussed in this study, cannot be drawn.Another possible disadvantage of a conservative approach may be that genetic information is not reported if screening criteria are not all met but might still have a proven medical benefit. For example, not reporting VUS is an internationally recognized approach for gNBS [4]; however, this reduces sensitivity (for the sake of specificity and positive prediction).Moreover, as with any screening, a negative gNBS result does not exclude a hereditary disease and cannot replace symptom-guided genomic diagnostics.Due to the complexity and limitations, the development of IC materials, possibly supported by chatbots and videos, should be given high importance in concrete program development.Finally, an economic evaluation of a future gNBS program is required, since cost-effectiveness is an important aspect for policy makers in funding of a public health program [7]. However, this was beyond the scope of this framework.Program management, centralized data collection, and learning systemFor the continuous optimization of future gNBS programs, they should ideally be designed as integrated public health and learning healthcare programs with centralized structures for data collection and the registry establishment. Regular analysis of key performance indicators is essential for data-driven evaluation and continuous optimization of the program, ideally supported by explainable AI-based algorithms. This is particularly important because changes in knowledge about natural history (e.g., phenotype diversity), or the establishment of new therapeutic interventions may change the achievement of screening criteria for a target disease, and the disease may thus be added to or removed from gNBS. Finally, as additional pilot studies may be conducted, their results, together with registry-based evaluations may lead to future re-assessments of individual criteria.Conclusion and OutlookThe presented multi-dimensional framework has been systematically developed by an expert panel representing medicine, ELSA, and patient representatives. It includes 11 selection criteria for target diseases and seven program management criteria for future gNBS public health programs. By applying a deliberately stringent and child-centered set of criteria, the framework aims to achieve high acceptance. Future work will focus on translating the selection criteria into a well-defined target disease list through a structured expert-driven curation, and iterative consensus process. The intended users of our proposed framework include clinical and research communities engaged in defining target diseases for gNBS, as well as policymakers, and advisory bodies tasked with program expansion, or legislative decision-making. Prospective use of the framework criteria in pilot gNBS programs will be decisive in proving their real-world value and shaping a framework capable of guiding future screening practice.ReferencesMütze U, Mengler K, Boy N, Gleich F, Opladen T, Garbade SF, et al. How longitudinal observationalstudies can guide screening strategy for rare diseases. J Inherit Metab Dis. 2022;45:889–901. https://doi.org/10.1002/jimd.12508Article CAS PubMed Google Scholar Dikow N, Ditzen B, Kölker S, Hoffmann GF, Schaaf CP. From newborn screening to genomic medicine:challenges and suggestions on how to incorporate genomic newborn screening in public healthprograms. 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Additionally, we thank our colleagues from the Institute for Medical and Data Ethics, previously Section Translational Medical Ethics (AG Winkler), the Institute for Human Genetics, the Section for Pediatric Neurology and Metabolic Medicine and the Newborn Screening Laboratory at Heidelberg University and Medical Faculty of Heidelberg University Hospital, as well as attendees of meetings and conferences where these criteria were presented, for their valuable feedback.FundingThe project was funded within the ELSA funding line of the German Federal Ministry of Education and Research (BMBF; since 2025 Federal Ministry of Research, Technology and Space: BMFTR), grant number 01GP2201A and 01GP2201B to E.W., R.M.-T., B.D., C.S., and S.K. The authors confirm independence from the sponsor; the content of the article has not been influenced by the sponsor. Open Access funding enabled and organized by Projekt DEAL.Author informationAuthor notesThese authors contributed equally: Elena Schnabel-Besson, Nicola Dikow, Karla Alex.These authors jointly supervised this work: Stefan Kölker, Christian P. Schaaf, Eva Winkler.Authors and AffiliationsHeidelberg University, Medical Faculty of Heidelberg, Center for Pediatric and Adolescent Medicine, Department of Pediatrics I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, GermanyElena Schnabel-Besson, Ulrike Mütze & Stefan KölkerHeidelberg University, Institute of Human Genetics, Heidelberg, GermanyNicola Dikow, Heiko Brennenstuhl & Christian P. SchaafHeidelberg University, Faculty of Medicine, Institute for Medical and Data Ethics, Heidelberg, GermanyKarla Alex, Lars Neth & Eva WinklerUniversity of Mannheim, Faculty of Law, Public Law, Law of Economic Regulation and Media, Mannheim, GermanyHannah Straub & Ralf Müller-TerpitzHeidelberg University, Institute of Medical Psychology, Heidelberg University Hospital, Heidelberg, GermanyElena Sophia Doll, Julia Mahal, Carlotta Julia Mayer & Beate DitzenDeutsche Interessengemeinschaft Phenylketonurie und verwandte angeborene Stoffwechselstörungen e.V, Heidelberg, GermanyTobias HagedornKindernetzwerk e.V, Aschaffenburg, GermanyHenriette HöglMartin Luther University Halle-Wittenberg, Department of Philosophy, Halle (Saale), GermanySascha SettegastNational Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Germany, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, GermanyEva WinklerAuthorsElena Schnabel-BessonView author publicationsSearch author on:PubMed Google ScholarNicola DikowView author publicationsSearch author on:PubMed Google ScholarKarla AlexView author publicationsSearch author on:PubMed Google ScholarUlrike MützeView author publicationsSearch author on:PubMed Google ScholarHannah StraubView author publicationsSearch author on:PubMed Google ScholarElena Sophia DollView author publicationsSearch author on:PubMed Google ScholarJulia MahalView author publicationsSearch author on:PubMed Google ScholarHeiko BrennenstuhlView author publicationsSearch author on:PubMed Google ScholarCarlotta Julia MayerView author publicationsSearch author on:PubMed Google ScholarLars NethView author publicationsSearch author on:PubMed Google ScholarTobias HagedornView author publicationsSearch author on:PubMed Google ScholarHenriette HöglView author publicationsSearch author on:PubMed Google ScholarSascha SettegastView author publicationsSearch author on:PubMed Google ScholarBeate DitzenView author publicationsSearch author on:PubMed Google ScholarRalf Müller-TerpitzView author publicationsSearch author on:PubMed Google ScholarStefan KölkerView author publicationsSearch author on:PubMed Google ScholarChristian P. SchaafView author publicationsSearch author on:PubMed Google ScholarEva WinklerView author publicationsSearch author on:PubMed Google ScholarContributionsConceptualization: E.S.-B., N.D., K.A., S.S., B.D., R.M.-T., C.P.S., S.K., E.W.; Funding acquisition: B.D., R.M.-T., C.P.S., S.K., E.W.; Investigation: E.S.-B., N.D, K.A., U.M., H.S., E.S.D., J.M., H.B., C.J.M., L.N., T.H., H.H., S.S., B.D., R.M.-T., C.P.S., S.K., E.W.; Project administration: K.A., L.N., S.S., B.D., R.M.-T., C.P.S., S.K., E.W.; Resources: B.D., R.M.-T., C.P.S., S.K., E.W.; Supervision: B.D., R.M.-T., C.P.S., S.K., E.W.; Visualization: E.S.-B., N.D, K.A., L.N., C.P.S., S.K., E.W.; Writing-original draft: E.S.-B., N.D, K.A.; Writing-review & editing: U.M., H.S., E.S.D., J.M., H.B., C.J.M., L.N., T.H., H.H., S.S., B.D., R.M.-T., C.P.S., S.K., E.W.Corresponding authorCorrespondence to Eva Winkler.Ethics declarationsCompeting interestsThe authors declare no competing interests.Ethical approvalFor this article no studies with human or animal subjects were performed. 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