Genomics is transforming health care but its implementation raises challenges. This paper reports a 2025 workshop on justice in the implementation of genomics for rare disorders. The workshop goals were to develop a consensus understanding of the problems faced by rare disease patients and families where justice is at stake, to achieve a shared perspective on support for rare disease patients, and to consider the implications for justice in several areas of rare disease genomics, in both research and healthcare. We heard about the diverse experiences and needs of patients. Inequity between different rare diseases is marked. The need for coordination of care for rare disease patients is under-recognized but good models of rare disease care exist. The value of conscientious professionalism to nurture a rare disease mindset needs to be emphasized in the training of each new generation of healthcare students//trainees. The circumstances of different population groups differ systematically. The needs of indigenous and other historically marginalised groups must also be addressed. However, the subordination of individuals to the benefit of the population (i.e. eugenics) must be resisted. Those engaged in genomics projects or diagnostics may need protection from hype and misuse of their personal data, There are different perspectives on the fair allocation of resources to healthcare and research for rare conditions. Health economics and health technology assessment can be practised equitably, so as to meet the challenges of rare disease clinical trials and address the needs of patients and communities.

The increasing number of expensive cell- and gene-based therapies (CGT) on the market have raised concerns regarding equal patient access, regarding both affordability and timely access. Health Technology Assessments (HTA) and Managed Entry Agreements (MEA) play a pivotal role in pricing and reimbursement (P R) decisions for expensive drugs in Europe, aiming to ensure patient access while optimizing resource allocation. However, discrepancies in HTA and P R processes lead to delayed, unequal or lack of access in different countries, exacerbating health inequalities across Europe. Though they facilitate access, MEAs introduce additional delays in pricing and reimbursement discussions, and their lack of transparency increases administrative burden and encourages pricing inequity, negatively affecting healthcare system sustainability. Recent legislative changes under Regulation (EU) 2021/2282 have established the Health Technology Assessment Coordination Group (HTACG), which will oversee mandatory joint clinical assessments in the coming years. This new legislation aims to streamline HTA processes across the EU. To address the ethical imperative of improving access equality for CGT in Europe, we propose further policy reforms including concurrent HTA, early benefit assessment, and incorporation of additional elements of value in HTA evaluations, alongside current initiatives to increase cross-border collaboration.

Background Gene replacement and gene editing therapies for cardiomyopathies are in early-phase clinical trials. However, limited data exist on patient perspectives. We assessed adult familial cardiomyopathy patient perspectives towards the clinical implementation of somatic genetic therapies. Methods Patients completed a demographic survey and semi-structured interview. A codebook was developed deductively and inductively, and thematic analysis was performed. Results Twenty-one participants with genetic and clinical diagnoses of either hypertrophic cardiomyopathy (17) or dilated cardiomyopathy (4) completed interviews. Participants ranged from age 38 to 80 (mean 57) and were 57% female. Four main themes influence participants’ decision-making for hypothetical pursuit of genetic therapies: 1) perceived clinical severity 2) potential for impact on quality of life 3) treatment details - safety, mechanism, and delivery 4) ethical and societal considerations. Those who described a severe clinical presentation expressed increased interest in genetic therapies and an increased willingness to accept risks for potential quality of life improvement, particularly if the therapy targeted the root cause and halted condition progression. Participants voiced uncertainties about the safety and long-term consequences of these therapies. Many participants believed that clinical severity should be prioritized for genetic therapies regardless of age; some felt younger individuals benefit more, avoiding lifelong treatment. Family members’ negative experiences with cardiomyopathies also influenced the decision-making process. A majority ranked genetic therapies over other treatment options, with 29% expressing hypothetical interest in participating in clinical trials or early adoption post-FDA approval. Ethical and societal concerns included misuse of these therapies, their egalitarian distribution, and loss of beneficial genetic traits. Conclusion Patients' support for and concerns about genetic therapies for cardiomyopathies highlight the need for clear communication of benefits, risks, uncertainties, and potential impact on quality of life. Including patients in discussions about the ethical and societal impacts of these therapies is essential.

There is little country-specific data about how the general public views gene editing therapies. In Autumn 2023 we randomly surveyed the Swiss public, using the Federal Register and stratifying by language region (German, French, Italian), gender and age. We present a representative sample of 3855 responses, including >4000 open-ended comments. When presented with 7 therapeutic options for somatic gene editing, 7% disagreed with all therapeutic options, and 35% supported them all. Most agreed with using somatic gene editing to cure life-threatening (76%) and debilitating diseases (70%); support declined as severity decreased or with later onset. Few supported somatic gene editing to enhance physical (6%) or cognitive (9%) abilities. In all scenarios, people were less likely to agree with gene editing of embryos. Notably, all therapeutic gene editing attitudes clustered, regardless of somatic vs. germline differentiations. Factor analysis also demonstrated two clusters for "support" and "caution" towards gene editing, and multivariate analysis demonstrated relationships with age, gender, religion and knowledge. When asked what influenced their views, the most endorsed reasons for feeling positively were 'views towards what it means to have a good life' (59.8%) and 'views about illness and suffering' (58.5%). Most selected "neutral" to describe religion's influence (68.9%) despite findings that those who endorsed high religiosity were less supportive and more cautious towards gene editing. Conclusions: Uncovering systematic differences in the attitudes towards specific therapies and the values shaping them underscores the importance of including peoples' voices in policy decisions in a country-specific manner.

Definition of the problemNewborn sequencing (NBSeq) offers the potential to detect hundreds of genetic conditions from infancy. On this basis, some consider NBSeq to be a revolutionizing equalizer, promising access to genomic testing for all newborns. However, the unique nature of equity in NBSeq has been oversimplified in the literature; the existing debate mainly highlights universal access as an automatic means of ensuring fair health outcomes.ArgumentsWe apply the Capability Approach (CA) to argue that providing access alone is not sufficient to achieve equity. Instead, the emphasis should be placed on developing capabilities that enable people to use NBSeq effectively and achieve meaningful health outcomes. Using capabilities as a measure of justice and eventually developing our own list, we provide an overview of systemic barriers within the process, including the underrepresentation of genomic data and variations in health literacy. This model allows us to extrapolate how these factors can affect individuals-particularly those from underserved backgrounds-in their ability to translate the benefits and outcomes provided by NBSeq into improved well-being throughout their lifespan.ConclusionThe CA provides a pluralistic perspective on equity in NBSeq by emphasizing an important distinction for justice in healthcare: the distinction between simply doing NBSeq and having the real freedom to choose to do NBSeq and then doing it. Equity in NBSeq requires refining justice by not only increasing access to the service itself but also ensuring the freedom for all to act on that justice in meaningful ways, leading to flourishing. Definition des ProblemsDie Genomsequenzierung von Neugeborenen (NBSeq) er & ouml;ffnet die M & ouml;glichkeit, eine Vielzahl genetischer Erkrankungen bereits im S & auml;uglingsalter zu erkennen. Auf dieser Grundlage betrachten einige die NBSeq als revolution & auml;ren Schritt hin zu mehr Gerechtigkeit, der allen Neugeborenen Zugang zu Genomtests verspricht. Doch die Einzigartigkeit der ,,Equity", der Chancengerechtigkeit, in der NBSeq wurde in der Literatur unzul & auml;ssig vereinfacht; in der derzeitigen Debatte wird vor allem der universelle Zugang als automatisches Mittel zur Gew & auml;hrleistung gerechter Gesundheitsversorgung hervorgehoben.ArgumenteWir wenden den Capability Approach (CA) an, um zu argumentieren, dass die Bereitstellung des Zugangs zu NBSeq allein nicht ausreicht, um Equity zu erreichen. Der Schwerpunkt sollte vielmehr auf die Entwicklung von F & auml;higkeiten gelegt werden, die es Menschen erm & ouml;glichen, NBSeq effektiv zu nutzen und eine sinnvolle Gesundheitsversorgung zu erzielen. Unter Verwendung von F & auml;higkeiten als Ma ss stab f & uuml;r Gerechtigkeit und schlie ss lich einer eigens erstellten Liste geben wir einen & Uuml;berblick & uuml;ber systemische Barrieren innerhalb dieses Prozesses, einschlie ss lich der Unterrepr & auml;sentation genomischer Daten und der Unterschiede in Gesundheitskompetenz. Anhand dieses Modells k & ouml;nnen wie extrapolieren, wie sich diese Faktoren auf Einzelpersonen - insbesondere aus unterversorgten Bev & ouml;lkerungsgruppen - auswirken k & ouml;nnen, wenn es darum geht, die Vorteile und Ergebnisse der NBSeq in ein verbessertes Wohlbefinden & uuml;ber ihre gesamte Lebensspanne hinweg umzusetzen.SchlussfolgerungenDer CA bietet eine pluralistische Perspektive auf Fragen nach Equity in der NBSeq, indem er eine wichtige Unterscheidung f & uuml;r die Gerechtigkeit in der Gesundheitsversorgung hervorhebt: die Unterscheidung dazwischen, zwischen der einfachen Durchf & uuml;hrung der NBSeq und der tats & auml;chlichen Freiheit, sich f & uuml;r eine NBSeq zu entscheiden und diese dann durchzuf & uuml;hren. Equity in der NBSeq erfordert einen verfeinerten Ansatz, in dem nicht nur der Zugang zur Dienstleistung selbst verbessert, sondern auch die Freiheit f & uuml;r alle gew & auml;hrleistet wird, auf sinnvolle Weise nach diesem gerechten Ansatz zu handeln.

BackgroundThe ability of machine learning (ML) to process and learn from large quantities of heterogeneous patient data is gaining attention in the precision oncology community. Some remarkable developments have taken place in the domain of image classification tasks in areas such as digital pathology and diagnostic radiology. The application of ML approaches to the analysis of DNA data, including tumor-derived genomic profiles, microRNAs, and cancer epigenetic signatures, while relatively more recent, has demonstrated some utility in identifying driver variants and molecular signatures with possible prognostic and therapeutic applications.MethodsWe conducted semi-structured interviews with academic and clinical experts to capture the status quo, challenges, opportunities, ethical implications, and future directions.ResultsOur participants agreed that machine learning in precision oncology is in infant stages, with clinical integration still rare. Overall, participants equated ongoing developments with better clinical workflows and improved treatment decisions for more cancer patients. They underscored the ability of machine learning to tackle the dynamic nature of cancer, break down the complexity of molecular data, and support decision-making. Our participants emphasized obstacles related to molecular data access, clinical utility, and guidelines. The availability of reliable and well-curated data to train and validate machine learning algorithms and integrate multiple data sources were described as constraints yet necessary for future clinical implementation. Frequently mentioned ethical challenges included privacy risks, equity, explainability, trust, and incidental findings, with privacy being the most polarizing. While participants recognized the issue of hype surrounding machine learning in precision oncology, they agreed that, in an assistive role, it represents the future of precision oncology.ConclusionsGiven the unique nature of medical AI, our findings highlight the field's potential and remaining challenges. ML will continue to advance cancer research and provide opportunities for patient-centric, personalized, and efficient precision oncology. Yet, the field must move beyond hype and toward concrete efforts to overcome key obstacles, such as ensuring access to molecular data, establishing clinical utility, developing guidelines and regulations, and meaningfully addressing ethical challenges.

BackgroundThere is growing consensus in favor of returning individual specific research results that are clinically actionable, valid, and reliable. However, deciding what and how research results should be returned remains a challenge. Researchers are key stakeholders in return of results decision-making and implementation. Multi-omics data contains medically relevant findings that could be considered for return. We sought to understand researchers' views regarding the potential for return of results for multi-omics data from a large, national consortium generating multi-omics data.MethodsResearchers from the Molecular Transducers of Physical Activity Consortium (MoTrPAC) were recruited for in-depth semi-structured interviews. To assess understanding of potential clinical utility for types of data collected and attitudes towards return of results in multi-omic clinical studies, we devised an interview guide focusing on types of results generated in the study for hypothetical return based on review of the literature and professional expertise of team members. The semi-structured interviews were recorded, transcribed verbatim and co-coded. Thematic trends were identified for reporting.ResultsWe interviewed a total of 16 individuals representative of 11 sites and 6 research roles across MoTrPAC. Many respondents expressed positive attitudes regarding hypothetical multi-omics results return, citing participant rights to their data and perception of minimal harm. Ethical and logistical concerns around the return of multi-omics results were raised, and they often mirrored those in the published literature for genomic return of results including: uncertain clinical validity, a lack of expertise to communicate results, and an unclear obligation regarding whether to return multi-omics results. With the exception of privacy concerns, respondents were able to give examples within multi-omics of how each point was relevant. Further, researchers called for more guidance from funding agencies and increased researcher education regarding return of results.ConclusionOverall, researchers expressed positive attitudes toward multi-omic return of results in principle, particularly if medically actionable. However, competing ethical considerations, logistical constraints, and need for more external guidance were raised as key implementation concerns. Future studies should consider views and experiences of other relevant stakeholders, specifically clinical genomics professionals and study participants, regarding the clinical utility of multi-omics information and multi-omics results return.

Informed consent is critical to the process of genetic counseling and is defined by respect for persons, self-determination, and voluntariness. This chapter will describe the legal and ethical aspects of informed consent, including some of the key legal cases that have shaped how medical informed consent occurs. This will include aspects of capacity, surrogate decision making, and consent/assent for children. The chapter will then apply these general principles of informed consent to the practice of genetic counseling and genetic testing. It will discuss various approaches to providing the educational content that underlies informed decisions, as well as recent research that helps determine the minimal concepts that are key to allowing a patient to make an informed decision about genetic testing. Finally, the chapter will discuss some of the differences between simple consent, informed consent, and the more complex shared decision-making (SDM) approaches.

Newborn screening for phenylketonuria began in the United States in the early 1960s, and it expanded one disease at a time until the development of tandem mass spectrometry. This technology allowed for screening many conditions simultaneously, but its uneven adoption led to wide disparities. A collaboration between the American College of Medical Genetics and Genomics and the US Health Resources and Services Administration resulted in a recommended uniform screening panel. Newborn sequencing (NBSeq) identifies many monogenic disorders, although to date it cannot identify all cases identified by tandem mass spectrometry. NBSeq has the potential to reduce diagnostic odysseys and increase health equity, but it could also exacerbate disparities and cause psychosocial and clinical harms due to overdiagnosis, oversurveillance, and/or overtreatment. By expanding beyond previously established public health screening principles, NBSeq also challenges the mandatory nature of current screening. In this review, we examine the promise and perils of NBSeq.

There are over 130 genetic counselor (GC) training programs documented in more than 30 countries. Some regions also have developed practice-based competencies and guidelines for accrediting GC training, often including lists of required curriculum items (for example: ACGC, CAGC, EBMG, HGSA). However, areas where genetic counseling is emerging or desired may struggle to create training approaches from these often-aspirational knowledge and skill development lists. In a collaborative effort between the Human Genome Organization (HUGO) Education Workgroup and the Transnational Alliance for Genetic Counseling (TAGC), we conducted a global consensus process to assess and deliberate over which knowledge and skills were broadly considered 'core' to the GC educational process. We utilized an online-modified Delphi process to survey a purposive global sample of GC education providers and members of credentialing boards from countries with established GC and medical genetics providers in areas where GC education is newly emerging. We identified a list of 64 potential topics through a literature review and review of relevant curriculum guidelines and professional competencies. We then assessed relevance in a 2-round survey process using the criteria of >80% agreement. Topics that met these criteria, including those that were borderline, were discussed in two online consensus meetings. We present the consensus list of 25 content topics across four major areas of knowledge and skills: counseling and communication, genetics and genomics, medical knowledge, and genetic counseling healthcare professional skills and knowledge that we propose should be included in the GC curriculum for countries where GCs are new or emerging. We also propose 11 additional "Tier 2" topics that could be considered depending on regional needs or as countries evolve the profession.

The U.S. Food and Drug Administration (FDA)’s platform technology designation program aims to streamline the development and approval process for advanced therapy medicinal products and is anticipated to be particularly beneficial for the development of gene therapies for rare and ultra-rare diseases. This is an exploratory interview study of Swiss-based perspectives, including insights from stakeholders in industry, academia, regulation, and reimbursement. The objective of our study is to document Swiss professionals’ views on the US platform designation program and to assess the acceptability and feasibility of a similar program in Europe. Participants identified benefits such as reduced redundancy in pre-clinical testing, standardization of manufacturing, and increased predictability of regulatory requirements. Concerns were raised about clinical assessment, commercialization strategies, and global regulatory alignment. Though participants anticipate it to increase innovation in the rare disease area, some raised the possibility that technologies may stagnate around a platform, or that designations may quickly become obsolete due to the speed of technological development. The introduction of the platform technology designation program in the US is a step towards increasing treatment options for ultra-rare diseases. While there is potential for platform designation to enable development in this area, its success will depend on addressing the outlined challenges.

Despite considerable scientific progress and the evolution of regulatory pathways to ensure safety and efficacy, US healthcare continues to see increasing health disparities. This suggests that clinical translation in of itself cannot be the only measure of its own success, especially when the most marginalized patients, are neglected in the development and implementation of medical innovations. This raises the question of whether a system that is narrowly focused on technical achievement can meet the moral obligations of medicine and public health. We argue that traditional technocratic standards are failing to integrate normative considerations into biomedical translation. What is needed is a translational domain that moves beyond safety and efficacy toward anticipating how proposed technologies will be effective in society as it exists. We propose an additional metric of success: translational justice.

The informed consent (IC) process is essential in genetic testing, yet IC materials are often difficult to read and understand, influencing patients’ decision-making. Large language models may improve the accessibility and clarity of these materials. We used GPT-4 to generate IC materials for Non-Invasive Prenatal Testing (NIPT) and hereditary breast and ovarian cancer testing (BRCA) in English, German, Italian, and Greek, using zero-shot prompting and retrieval-augmented generation. Healthcare providers evaluated GPT-4-generated and human-generated materials using a previously published framework. GPT-4 performed well on structured components, such as explaining the purpose and benefits of testing, but struggled with nuanced ethical and contextual content. Respondents overall preferred human-written materials, underscoring limitations in current GPT-4-generated material for health communication in the genetic testing context. GPT-4’s performance in German, Italian and Greek was generally weaker than in English, highlighting potential language-specific challenges in GPT-4-generated IC content.

Genomic sequencing technologies are increasingly used in health. Improvements in sequencing technology and reductions in its cost mean that the default approach is frequently to obtain more genomic information rather than less. However, the volume of genomic data does not necessarily track with its ability to be interpreted, and it is widely acknowledged that genomic sequencing can increase, rather than resolve, uncertainty for patients and their families. Uncertainty in genomics impacts both professionals and patients. The near certainty of uncertainty should be factored into all elements of the genetic and genomic testing process, from initial test offer to longer‐term follow‐up. In some circumstances, uncertainty can provide a valid reason to restrict the scope of testing. Given its resource implications, uncertainty in genomics should also be considered at the health system level. Ethical provision of genomic sequencing in health‐care necessitates both planning for uncertainty and minimising its impact on all stakeholders. The integration of genetic and genomic testing into various medical specialties is increasing, making genetic information more accessible to patients. Despite technological advancements, genetic and genomic testing often introduces new uncertainties. Different dimensions of uncertainty in genomics include its sources (probability, ambiguity, complexity), issues (scientific, personal, practical) and loci (patients, providers, policymakers). Patients and their families may experience emotional and psychological impacts due to uncertain or unexpected results from genetic and genomic tests. Genetic counsellors play a crucial role in helping patients understand and cope with the uncertainties and implications of genetic and genomic testing. Ethical responses to genomic uncertainty involve promoting resilience, patient welfare, autonomy and solidarity, while managing expectations and providing support. Ethically responding to uncertainty also requires considering uncertainty at all stages of the testing process, including decisions on whether to undergo testing and whether or how to disclose uncertain information. Inherent uncertainties in genomic testing need to be considered in all settings where genomic information is offered, not just clinical care. Managing genomic uncertainty effectively is essential for the sustainability and stability of health systems, including considerations of resource allocation and environmental impact. The volume of genomic data does not necessarily correlate with its interpretability, and this should be factored into the genetic and genomic testing process from initial test offer to long‐term follow‐up.

Diagnoses of multisomy sex chromosome aneuploidies (SCA) have increased in primary care settings following the implementation of genetic testing in pediatric practice. Multiple studies have explored the impact of how the diagnosis is delivered, finding that it impacts how families and affected individuals perceive and adapt to the diagnosis. Despite a growing body of empirical evidence on the patient experience, there has been limited published guidance on optimal diagnosis delivery. We aimed to review the patient experience literature and synthesize recommendations for delivering a pediatric diagnosis of a multisomy SCA.

BACKGROUND:The diagnosis of supernumerary X & Y chromosome variations has increased following the implementation of genetic testing in pediatric practice. Empirical evidence suggests that the delivery of the diagnosis has a lasting impact on how affected individuals and their parents perceive and adapt to the diagnosis. The purpose of this review is to synthesize the literature to obtain useful recommendations for delivering a pediatric diagnosis of a sex chromosome multisomy (SCM) based upon a growing body of quantitative and qualitative literature on patient experiences.METHODS:We conducted an integrative literature review using PubMed, Web of Science and CINAHL employing keywords "genetic diagnosis delivery," "genetic diagnosis disclosure," "sex chromosome aneuploidy," "Klinefelter syndrome" or ""47, XXY," "Jacob syndrome" or "47, XYY," "Trisomy X," "Triple X" or "47, XXX," and "48 XXYY from January 1, 2000, to October 31, 2023.RESULTS:Literature supports that patients and parents value the provision of up-to-date information and connection with supportive resources. Discussion of next steps of care, including relevant referrals, prevents perceptions of provider abandonment and commitment to ongoing support. Proactively addressing special concerns such as disclosing the diagnosis to their child, family, and community is also beneficial. Tables are provided for useful information resources, medical specialties that may be required to support patients, and common misconceptions that interfere with accurate information about the diagnosis.CONCLUSION:Patient experiences suggest there should be heightened attention to diagnosis delivery, in reference to the broader ethical and social impacts of a SCM diagnosis. We present recommendations for optimal disclosure of a SCM diagnosis in early and late childhood, adolescence, and young adulthood.

BACKGROUND:There are intense discussions about the ethical and societal implications of biomedical engineering, but little data to suggest how scientists think about the ethics of their work. The aim of this study is to describe how scientists frame the ethics of their research, with a focus on the field of molecular systems engineering. METHODS:Semi-structured qualitative interviews were conducted during 2021-2022, as part of a larger study. This analysis includes a broad question about how participants view ethics as related to their work, with follow up probes about the topics they consider most important. Interviews were transcribed, inductively coded by two researchers to consensus, and analyzed thematically. RESULTS:Twenty-four scientists participated in the study. Interviewees hold positions as professors, principal investigators, and senior staff researchers in universities or research institutes in the United States and Europe. Among those scientists who reported reflecting on ethical considerations in their work, many equated ethics with research ethics topics (e.g., safety, replicability), or with regulation and guidelines. Participants expressed the view that ethical issues are primarily relevant for clinical trials of bioengineered products, or for those working with animal or human subjects. Scientists described their research as "too early" or "not examining anything living" with regard to ethical reflection. Finally, many felt that ethics is seen as territory for experts and therefore beyond scientists' competencies. CONCLUSIONS:Molecular systems engineering scientists currently focus on regulatory aspects as the framework for their ethical analyses. They describe using a framework to define when life arises, as a means to determine when further ethical engagement is warranted. Further research is needed to investigate how scientists relate to the ethics of their scientific work, and build consensus around concepts of life, autonomous behavior, and physiological relevance of bioengineered systems.

We conducted an exploratory survey of genetic counselors internationally to assess similarities and differences in reported practice activities. Between November 2018 and January 2020 we conducted a mass emailing to an estimated 5600 genetic counselors in different countries and regions. We obtained 189 useable responses representing 22 countries, which are included in an aggregate manner. Data from countries with 10 or more responses, comprising 82% of the total (N = 156), are the primary focus of this report: Australia (13), Canada (26), USA (59), UK (17), France (12), Japan (19) and India (10). Twenty activities were identified as common (≥74%) across these countries, encompassing most subcategories of genetic counseling activity. Activities with most frequent endorsement include: reviewing referrals and medical records and identifying genetic testing options as part of case preparation; taking family and medical histories; performing and sharing risk assessment; and educating clients about basic genetic information, test options, outcomes and implications, including management recommendations on the basis of the test results. Genetic counselors also consistently establish rapport, tailor the educational process, facilitate informed decision making and recognize factors that may impact the counseling interaction. The least endorsed activities were in the Medical History category. Notable differences between countries were observed in the endorsement of 33 activities, primarily in the Contracting and Establishing Rapport, Family History, Medical History, Assessing Patients Psychosocially and Providing Psychosocial Support categories. Generalizations about international practice patterns are limited by the low response rate. However, this study is, to our knowledge, the first to systematically compare the clinical practice and specific activities of genetic counselors working in different countries.

Sex chromosome aneuploidies (SCAs) are among the most common chromosomal conditions. There is little scholarship on how adolescents and young adults (AYAs) affected by SCA engage with and adapt to their diagnosis. In order to understand how AYAs adapt to a SCA diagnosis, we conducted a secondary analysis of qualitative interviews with AYAs. Eight in-depth semi-structured interviews with individuals with a diagnosis of 47,XXY, 47,XXX, and 48,XXYY were analyzed for iterative themes related to adaptation to a SCA diagnosis in accordance with standard qualitative methodology. Our findings suggest that the process of adaptation is highly variable and complex and is mediated by external factors including diagnosis delivery and community support. Factors associated with adaptation include feeling understood and supported by healthcare providers; researching the condition; receiving hormone replacement therapy; and receiving support from a community of peers. As access to prenatal and pediatric genetic testing continues to expand, non-genetic pediatric providers are increasingly likely to interact with individuals with SCAs as part of their initial diagnostic odyssey or ongoing medical management. Understanding the diversity of lived experiences of AYAs with SCAs is helpful for healthcare providers to facilitate holistic care and provide meaningful support to patients.