Nursing's Role in Advancing Care for Rare Genetic Diseases.

Nursing’s role in advancing care for rare genetic diseases - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Search Log in Primary site navigation Search Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Nurs Clin North Am . Author manuscript; available in PMC: 2026 Jun 1. Published in final edited form as: Nurs Clin North Am. 2025 Mar 3;60(2):349–368. doi: 10.1016/j.cnur.2024.12.005 Nursing’s role in advancing care for rare genetic diseases Andrew A Dwyer 1, 2 , Suja Somanadhan 3 Author information Article notes Copyright and License information 1 Associate Professor, William F. Connell School of Nursing, Boston College, Chestnut Hill, Massachusetts, USA 20476 2 Investigator, P50 Massachusetts General Hospital – Harvard Center for Reproductive Medicine, Boston, MA 3 Associate Dean for Global Engagement and Associate Professor, UCD School of Nursing Midwifery and Health Systems, University College Dublin, Dublin 4, Ireland Andrew A. Dwyer, PhD, FNP-BC, FNAP, FAAN, Boston College William F. Connell School of Nursing, 140 Commonwealth Avenue, Maloney Hall 364, Chestnut Hill, Massachusetts, USA 20476 Dr Suja Somanadhan PhD, MSc, BA, RCN, RGN, RNT, UCD School of Nursing, Midwifery and Health Systems, Room B.312, UCD Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland ✉ Corresponding Author: Andrew A. Dwyer, PhD, FNP-BC, FNAP, FAAN, Boston College William F. Connell School of Nursing, 140 Commonwealth Avenue, Maloney Hall 364, Chestnut Hill, Massachusetts, USA 20476, andrew.dwyer@bc.edu Issue date 2025 Jun. Keywords: genetic testing, genomics, health disparities, nursing care, patient empowerment, rare diseases PMC Copyright notice PMCID: PMC12068770  NIHMSID: NIHMS2041838  PMID: 40345765 The publisher's version of this article is available at Nurs Clin North Am Introduction Rare diseases (hereafter referred to as RDs) are heterogeneous conditions characterized by low frequency and high complexity. Notably, more than 70% of RDs are genetic in etiology. 1 There is no singular definition of what makes a disease “rare” ( Box 1 ). In the United States (U.S.), the 1983 Orphan Drug Act defines a RD as one that affects fewer than 200,00 Americans while in the European Union and other parts of the world the definition is fewer than 5 in 10,000 individuals (i.e., 1 in 2,000). 2 While individually rare, there are more than 7,000 identified RDs and 250–280 new RDs are described annually. Globally, RDs affect an estimated 3.5–5.9% of the population, or roughly 263–446 million individuals - including approximately 25–30 million Americans and 36 million Europeans. 1 , 3 Patients and families living with RDs have considerable physical, psychological, and social challenges making RDs a significant global public health and policy priority. 4 In 2021, the United Nation’s (U.N.) adopted its first resolution addressing the challenges faced by individuals with RDs and their families, urging member states to ensure access to safe and affordable health services, especially at the primary care level. 5 Box 1. Definition of key terms. Rare disease A disease, disorder, or syndrome characterized by low frequency and high complexity. Definitions vary in North America (United States: affecting fewer than 200,000 people, Canada and Mexico: affects fewer than 1 in 2,000 people). Diagnostic odyssey A term describing the lengthy, arduous process of receiving an accurate diagnosis. It often involves multiple healthcare encounters, specialist consultations, diagnostic tests, and misdiagnosis. Next-generation sequencing New technologies employing high throughput, massive parallel sequencing to sequence DNA and RNA. Software (bioinformatics) is used to analyze sequencing results to identify variants (mutations). Bioinformatics An interdisciplinary field of science that uses computing technology to understand biologic data. Software and algorithms (pipelines) are developed to analyze, annotate, and interpret large sets of sequencing data on DNA and amino acid sequences. Mendelian disorder A genetic disorder caused by a pathogenic variant in a single gene that may be inherited in families. Sometimes termed monogenic disease. Orphan drug A pharmaceutical (drug) developed to treat a rare disease. Such drugs are typically underdeveloped commercially due to limited profitability (i.e., rarity of the condition and small patient population). CRISPR Short for c lustered r egularly i nterspaced s hort p alindromic r epeats, CRISPR is a form of genome editing in living organisms. Health disparities Preventable differences in disease burden (including injury/violence) or opportunities to achieve optimal health experienced by disadvantaged populations resulting from inequities in social, political, economic, and environmental resources. Social determinants of health Environmental conditions that affect wide-ranging health, functioning, and quality-of-life outcomes/risks. Five domains include economic stability, education access/quality, healthcare access/quality, neighborhood and built environment, and social/community context. Person-centered care An approach to healthcare that engages patients in their care. Clinician-patient collaboration aims to develop a care plan that is responsive to patient needs and priorities. Shared decision-making An approach where clinicians and patients review and discuss the best available evidence and consider available options for a health decision. Patients are supported to make ‘high quality’ decisions (i.e., informed and aligned with preferences). Co-creation A process that actively involves end-users (patients) from beginning to end to gain insights, generate ideas, and identify/refine potential solutions. It is sometimes referred to as “user-centered design’, “design thinking” or “co-design”. Patient-public involvement A collaborative practice that includes patients, family/caregivers, and members of the public in setting a research agenda (i.e., what is studied and the approach) with clinicians and researchers. Patient centered medical home A model of care that places the patient at the forefront to strengthen relationships between patients and care teams. The model is associated with improved quality and patient/staff satisfaction as well as decreased costs. Open in a new tab Rare diseases are often overlooked and neglected and thus, sometimes referred to as “Orphan diseases”. One reason is that prevalence varies widely across individual RDs. The most common point prevalence is 1–5 per 10,000 yet prevalence ranges from 5–80 per 100,000. 1 For example, sickle cell disease is a rare condition that affects roughly 245,000 individuals according to the World Health Organization (WHO) while other conditions occur much less frequently (e.g., lysosomal storage disorders) and others are considered ultra-rare affecting only a handful of individuals globally. Moreover, some conditions may be ‘rare’ in some regions but not in others. One such example is tuberculosis which is rare in Europe and the United States yet is one of the top ten causes of death globally. The vast majority of RDs are genetic in etiology and roughly 70% are present at birth or have pediatric onset. 1 Indeed, more than half of people affected by a RD are children and approximately 30% of them die before five years-of-age. 3 Rare diseases are typically multisystemic and chronic with significant associated physical, sensory, and/or intellectual disability. 6 , 7 Such impairments have significant emotional impact on families and contribute to social isolation and diminished quality of life. 6 Patients and families with RDs are challenged by poor understanding of RDs, delays in diagnosis, lack of access to specialist care, and lack of effective treatments or cure. The limited knowledge of RDs contributes to delays in diagnosis and the ‘diagnostic odyssey’ ( Box 1 ). On average, patients have to wait longer than 5-years to get a correct diagnosis and more than 40% are misdiagnosed along the way. 3 Specialists who are knowledgeable in RDs are scarce, patients and their families may find it challenging to gain access to services due to geographic distance. Additionally, 95% of RDs have no approved treatment or cure. 8 Since the passing of the 1983 Orphan Drug Act, the U.S. Food and Drug Administration (FDA) has approved drugs for more than 800 orphan indications. 9 The European Union (E.U.) has approved more than 150 orphan drugs yet the number of approved medications for children with RDs is frustratingly low with only 56 pediatric drug approvals to date. 8 The cost of care for RDs is significant. 10 Studies demonstrate that children and adolescents with RDs have a disproportionately higher cost burden on hospital systems. 11 – 13 McCandless and colleagues reported that RDs accounted for 34% of all hospital admissions with 40% longer hospitalizations accounting for 50% of total hospital charges. 11 Compounding healthcare costs is the fact that caregiver(s) may not be able to work and patients may face discrimination when seeking employment. 6 , 14 In summary, RDs present a range of physical, cognitive, social, and financial challenges that have significant impact on population health outcomes. As such, psychological and emotional well-being of patients with RDs is a crucial aspect of comprehensive care. 6 , 15 This review provides an overview of nursing’s essential role in providing care, emotional support, counselling, advocacy, facilitating peer-to-peer support, and helping patients and families navigate the complexities of living with a rare disease. Healthcare disparities in rare genetic disorders The U.S. Centers for Disease Control and Prevention considers health disparities preventable differences in disease burden and opportunities for optimal health. 16 In the context of RDs, patients and families are faced with a variety of challenges and inequities that place them in the realm of health disparities. 17 First, individuals with RDs are geographically dispersed, contributing to isolation and difficulty in finding and accessing care. Second, RDs are poorly understood and clinicians typically have limited knowledge of typical signs and symptoms of RDs - contributing to delays in diagnosis, misdiagnosis, an decreased wellbeing and quality of life. Moreover, the so-called ‘diagnostic odyssey’ can erode confidence and trust in healthcare providers and health systems. 18 In contrast, timely diagnosis is associated with decreased treatment costs, fewer hospitalizations, and less financial hardship for families. 18 Third, patients with RDs lack effective treatments or cure. Only ~5% of RD diagnoses have an approved treatment. 8 If a treatment is available, it is often for an “off-label” use meaning the treatment has not been approved for that indication. Additionally, the cost of treatments can be significant. Technologies such as gene therapy (e.g., CRISPR – Box 1 ) hold significant promise for many rare, Mendelian (i.e., single gene) RDs. However, the cost can be prohibitive. For example, Hemgenix is an effective gene therapy that leverages an adenovirus viral vector to treat hemophilia B - yet it can cost up to $3.5 million to treat a case in the U.S. 18 Taken together, such factors mean that patients with RDs are often ‘locked out’ of care. A 2014 study estimated that more than half of individuals suspected to have a rare genetic disorder remained undiagnosed. 19 Technologic advances including high throughput next-generation sequencing (NGS) technologies, bioinformatic approaches ( Box 1 ), and mainstreaming of genetic testing have helped shorten the diagnostic odyssey for many. Advances now make diagnosis possible in weeks to months instead of years (or not at all). Unfortunately, access to such testing to speed diagnosis is often not equitable. Geography poses major barriers to access particularly for individuals in rural communities – a significant portion of underserved and underrepresented individuals. 20 Thus, it is not surprising that diversity and equity are key topics for RD communities. 21 Equity in practice means meeting people’s specific needs and eliminating barriers preventing their full participation in society. For people living with a RD, equity means social opportunity, non-discrimination in education and work, and equitable access to health, social care, diagnosis, and treatment. 21 Findings from the “Genomic Answers for Kids” program provides promising results for making access to genetic testing more equitable for rural populations. 20 The novel program provided early direct-to-provider access to NGS testing as an alternative to the traditional primary care referral to a genetics specialist model of care, demonstrating shortened time to diagnosis (minimum of 5.5 months) providing an important proof of concept for addressing equity for pediatric RDs in rural communities. 20 Similarly, advances in artificial intelligence and machine learning (AI/ML), such as AI-MARVEL 22 for diagnosing Mendelian (i.e., single gene) disorders ( Box 1 ), are enabling researchers to train models (algorithms) based on large datasets to help streamline diagnosis and identify possible avenues for treatment. 23 Technological advances are promising for RDs, yet such advances are far from being a panacea for ameliorating disparities. It is critical to tackle the stigma, discrimination, and social marginalization faced by individuals and families affected by RDs. 24 Each year, the National Organization for Rare Disorders (NORD) and the European Organization for Rare Diseases (EURORDIS) use Rare Disease Day (February 28 th ) to echo the WHO mandate and call for action to create equal opportunities for individuals with RDs to realize their full participation in family, work, and social life. Access to education and lifelong learning, including higher education, has become a high priority to ensure that no one is left behind. 6 Ethical and legal considerations are also paramount in the care of patients with RDs. Nurses must ensure that care is delivered ethically, with a focus on patient autonomy, informed consent, and respect for patient rights. Indeed, this notion is coherent with the American Nurses Association (ANA) code of ethics. 25 Nurses must be knowledgeable about the legal aspects of healthcare, including patient rights and relevant healthcare laws, to advocate effectively for their patients and help surmount disparities for RDs. The role of nursing in precision healthcare and rare genetic disorders Advances in genomics (e.g., NGS) have significantly impacted the field of RDs and have spawned precision healthcare – yet not all groups have benefited from genomic discovery and precision healthcare. Nurses are the most numerous of trained health professionals with a global workforce of about 29 million. 26 In parallel, Gallup Polls have ranked nursing as the most trusted and ethical of professions for the past 22 years. 27 Thus, nurses have a key role in realizing the full potential of genomic discovery to improve outcomes in health and well-being equitably. 28 , 29 Notably, social determinants of health ( Box 1 ) are known to contribute to inequality in patient outcomes and underserved and minoritized individuals are less likely to undergo genetic testing and get a genetic diagnosis. 21 Barriers to genetic diagnosis may be present at many points along the care continuum, from suspicion of a genetic disorder, referral to a genetic specialist, or evaluation by a genetic specialist (i.e., genetic counselor), which impede genetic testing and identifying a genetic diagnosis. 21 Moreover, if a genetic test is undertaken, interpreting the pathogenicity (i.e., disease-causing) of a variant may not be possible. For example, reference data used to interpret gene variants is lacking for traditionally underrepresented racial/ethnic groups. 21 Thus, it may be challenging (or impossible) to determine if a variant is benign or pathogenic for an individual in a minority group. Patient-related factors including patient understanding of genetic testing, lack of trust in providers, and inadequate insurance coverage, also pose challenges to timely diagnosis. Such barriers are insidiously harmful as genetic diagnosis can improve quality of life, enable access to key services and support, and inform family reproductive decision-making. 30 Thus, nurses have an ethical imperative to screen for social determinants of health and address disparities in RDs. According to the ANA, “Nursing integrates the art and science of caring and focuses on the protection, promotion, and optimization of health and human functioning; prevention of illness and injury; facilitation of healing; and alleviation of suffering through compassionate presence.” 31 Nurses also have a critical role in addressing the complex, physical and psychosocial needs of patients and families affected by RDs. 7 Nursing is directly implicated in six key areas of quality, comprehensive care for RDs: novel care delivery models, care team effectiveness, providing information (therapeutic education), enabling support systems, empowering patients’ voices in care, and advocacy ( Figure 1 ). Figure 1. Open in a new tab Targets for enhancing psychosocial well-being and quality of life in rare disease care. Avenues for improving care and enhancing psychosocial well-being and quality of life include: ( 1 ) Models of care that support access and continuity of care; ( 2 ) Effective multidisciplinary teams to manage complex rare diseases; ( 3 ) Providing accurate, up-to-date information in ways that are understandable to patients/families; ( 4 ) Linking patients/families with psychosocial supports to combat stigma, shame, and isolation; ( 5 ) Empowering patients to be active participants in health decisions and care plans; ( 6 ) Amplifying patient perspectives to inform research agendas and shaping rare disease policy. EHR: electronic health record. Image credit: thenounproject Models of rare disease care In terms of models of care for RDs, a number of approaches have been proposed to meet the unique needs of this patient population. 32 , 33 One such model, the Care Continuum Model, focuses on three concepts around care coordination: telehealth (to span geographic barriers to care), integration of care and research (to speed diagnosis and accelerate development of novel treatments), and improving patient–clinician-researcher collaboration. 34 Care coordination is critical for RDs as patients/families are challenged to navigate a complex healthcare ecosystem and juggle multiple specialists. Nurses can play a crucial role in mitigating care coordination challenges. 35 Indeed, robust data support the effectiveness of nurse navigator/nurse care coordinator roles. 36 Such roles can facilitate joint visits (i.e., multiple, cascading specialist appointments during a single visit). Similarly, nurses provide telehealth and/or virtual consultations to mitigate geographic barriers and travel burdens. 37 Evidence demonstrates that advance practice nurses (i.e., nurse practitioners) can effectively coordinate care across complex care pathways and help patients/families navigate the healthcare system. 38 Similarly, nurses play a vital role in the patient-centered medical home model 39 and structured transitional care that moves adolescents and young adults from pediatric to adult-oriented care. 40 Effective care teams Nurses contribute to care effectiveness by supporting effective within-team and interprofessional communication across specialists and through a person- and/or family-centered approach to care. Providing person-centered care (PCC) is a key means for nursing to advance quality care of RDs. Briefly, PCC relies on effective provider-patient communication that empowers patients and facilitates the creation of care plans that are responsive to the individual’s goals, values and preferences. 41 The six key components that underpin PCC include care that: i.) empowers patients, ii.) improves quality of life, iii.) supports independence, iv.) promotes positive well-being, v.) honors choice, and vi.) promotes respect. 42 Given the estimated 7,000 distinct RDs, each patient’s experience can be significantly different. Thus, a person centered approach enables a tailored approach (a tenet of precision healthcare) that is threaded through the nursing process from assessment, to diagnosis, to planning, to implementation, to evaluation. Patient needs for information Nurses can respond to unmet patient/family informational needs by connecting them with trusted, reliable information sources ( Box 2 ). Patients and families need information on available treatments and therapies. However, as most RDs do not have approved treatments, more research is required to identify new therapeutics and advance them through the approval process. 9 Of note, RDs pose particular challenges for clinical trials (i.e., limited, geographically dispersed patient populations). 43 Nurses can help patients identify clinical trials ( Box 2 ) and help clarify potential misconceptions regarding the “therapeutic misconception” (i.e., that an investigational drug is not necessarily effective or a viable treatment) and support high-quality decisions (i.e., informed and aligned with values and preferences) for informed consent prior to participating in a clinical trial. Nurses should use accurate, up-to-date information to inform therapeutic education ( Box 2 ). Additionally, therapeutic education should be delivered with careful attention to health literacy and numeracy incorporating visual aids and infographics to facilitate understanding. 44 Further, best practices include using “teach back” 45 , 46 to enable comprehension and support high-quality decisions. Box 2. Rare disease resources and information. Resources National Organization for Rare Disorders (NORD) https://rarediseases.org/ Canadian Organization for Rare Disorders (CORD) https://www.raredisorders.ca/ European Organization for Rare Diseases (EURORDIS) https://www.eurordis.org/ Information, Support, & Advocacy Orphanet https://www.orpha.net/ Genetic Alliance https://geneticalliance.org/ Genetic & Rare Diseases Information Center https://rarediseases.info.nih.gov/ Gene People https://genepeople.org.uk/ Global Genes https://globalgenes.org/rare-list/ Every Life Foundation https://everylifefoundation.org/ Medics 4 Rare Diseases https://learn.m4rd.org/ Rare Diseases International https://www.rarediseasesinternational.org/ Rare Disease Diversity Coalition https://www.rarediseasediversity.org/ Unique https://rarechromo.org/ Research International Rare Diseases Research Consortium (IRDiRC) https://irdirc.org/ Undiagnosed Disease Network https://undiagnosed.hms.harvard.edu/about-us/ Rare Disease Foundation https://rarediseasefoundation.org/ Rare Diseases Clinical Research Network https://www.rarediseasesnetwork.org/ Orphan drugs U.S. Food and Drug Administration (FDA) https://www.fda.gov/patients/rare-diseases-fda European Medicines Agency (EMA) https://www.ema.europa.eu/en/homepage Clinical Trials Clinical Trials https://clinicaltrials.gov/ Health Canada Clinical Trials Database https://health-products.canada.ca European Rare Disease Research Coordination & Support Action https://erica-rd.eu/ Open in a new tab Psychosocial support for well-being Patients and families affected by RDs often experience significant social and financial consequences contributing to feelings of guilt, shame, marginalization, and stigmatization. 24 , 47 A such, nurses can play an integral role in providing direct emotional support and linking patients/families to disease-specific patient organizations ( Box 2 ) and plugging them into community-based resources and charities. 14 The role of peer-to-peer support should not be underestimated. 48 While healthcare providers may understand genetics, pathophysiology, and treatments they do not understand the day-to-day lived experiences of patients who live with RDs. Peer-to-peer support can help reduce ‘othering’ and stigmatization while providing much needed psychological, emotional, and psychosocial support and provide opportunity for crowdsourcing solutions to unmet needs. 15 , 49 Patient involvement in care Patients living with RDs become experts in their condition. 50 Such expertise represents untapped potential and underscores the benefits of close patient-provider collaboration and shared decision-making ( Box 1 ). Thus, it is important for nurses and other healthcare providers to respect patient expertise 50 and actively engage patients in creating a plan of care - a key tenet of PCC. The modern, fast-paced, ecosystem of healthcare delivery means that providers are often pressed to have adequate time to address all patient concerns during a consultation. Moreover, as patients/families are geographically dispersed, geography can pose significant challenges in terms of time and cost for regular appointments. The electronic health record (EHR) and accompanying health portals provide ways to bridge time and geographic barriers for patients to communicate with busy providers. Such “high-tech” solutions can facilitate communication and foster “high touch” care experiences for patients. 51 Empowering the patient voice – patient public involvement Empowerment has long been lauded as a crucial for the RD community. 52 For RDs, individuals must be empowered to have a voice in advocating for care and research priorities as well as in shaping policy. 53 Such patient public involvement ( box 1 ) (i.e., patient advisory boards) can inform priorities for improving care and research. 54 , 55 Notably, such advisory boards must be mindful of health equity and intentionally include voices and perspectives of diverse (i.e., underrepresented and minoritized) individuals. 21 Patient organizations can help shape RD research agendas 54 , 56 , 57 and such organizations are key stakeholders in clinical trial design. 58 Some patient organizations have gone even further, sponsoring research in a specific RD and playing and active, participatory role in research. 59 In the larger societal context, patient organizations are crucial for lobbying and advocating for policies that respond to patient needs and priorities. 60 As the most numerous of trained health professionals, nurses can have an essential role in advocating for policies that support patients and families. Further, nurses can be key patient advocates connecting patients/families with RD organizations ( Box 2 ) and joining lobbying effort to promote a just RD policy agenda. Case exemplars of nursing impact on rare genetic diseases Nursing’s role caring for patients and families affected by RDs is multifaceted and dynamic, requiring a balance of clinical expertise, skilled therapeutic education, effective communication, patient engagement, emotional intelligence, advocacy, and continuing education. Nurses can be indispensable in providing the specialized care to meet the needs of patients/families living with RDs. We describe two exemplar cases, one advanced practice nurse (APRN) and one registered nurse (RN), respectively, to demonstrate how nurse-led interventions, community engagement, and research can improve comprehensive, quality care for RDs that empowers patients, amplifies their voice, and enhances their psychosocial well-being and quality of life. Moreover, the nursing interventions described in each exemplar span the continuum of RD care and addressing health disparities. An international nursing collaboration recently developed the ACCESS (Advocating, Coping, Communication, cascadE Screening, and Surveillance) framework. The framework drew on nursing work in RDs and thus, has direct relevance for bridging RD disparities. Importantly, ACCESS was created for practicing nurses to highlight the critical role nurses play in working to end disparities in genomic and precision healthcare. 61 Exemplar 1 (APRN): Congenital hypogonadotropic hypogonadism (Kallmann syndrome) Congenital hypogonadotropic hypogonadism (CHH) is a rare endocrine disorder (1 in 10,000–48,000) characterized by absent/incomplete puberty and infertility. 62 It is genetically heterogenous with more than 60 genes identified to underlie the condition – making diagnosis challenging. The clinical presentation is also highly variable with a range of reproductive (i.e., cryptorchidism, micropenis) and non-reproductive phenotypes including anosmia (termed Kallmann Syndrome), sensorineural hearing loss, unilateral renal agenesis, as well as dental and skeletal defects. 63 Unlike many RDs, treatments are available and individuals with CHH do not have decreased life expectancy. 62 However, CHH is often diagnosed late and patients typically struggle with a range of psychological, emotional, social, and psychosexual issues that contribute to significant anxiety, depression, and diminished health-related quality of life (HR-QoL). 49 , 64 – 67 Nurse-led work with the CHH patient community has focused on developing partnerships with patient leaders to better understand the unmet health and educational needs of patients 49 , 64 – 67 and identify patient priorities for improving CHH care. This work led to the creation of a Patient Advocacy Working Group in the international consortium studying CHH (COST Action BM1105) 68 and helped found a formal patient organization (“I Am HH”, www.Iamhh.org ) that received NORD “Gold Member” status in recognition of ongoing collaboration between clinicians, centers of excellence, researchers, and patients. Patient partnerships helped empowering patients with CHH by bringing previously unheard patient voices to the forefront and conducting a first-of-its kind CHH patient needs assessment. 49 The needs assessment identified unmet patient health and education needs from a patient lens. The patient leader, Mr. Neil Smith, then helped create a roadmap for improving care of CHH ( Figure 2 ). 66 Figure 2. Open in a new tab Co-created roadmap for improving CHH care and related components of person-centered care. Five elements were identified for improving care for CHH: 68 earlier identification and treatment, empowering self-management and treatment adherence, sealing gaps and cracks in care, support and therapeutic education, and leveraging patient expertise and internet reach. The six components of person centered care (PCC) are identified for each target. Image credit: thenounproject To enable earlier diagnosis and treatment, evidence-based approaches to diagnosis and treatment were published and disseminated 62 and a model for comprehensive CHH care was developed that encompassed disease management, health promotion, therapeutic education, and well-being. 69 , 70 Recognizing patients are experts in their condition, clinicians, researchers, and patients used ‘design thinking” (i.e., user-centered design) to co-create lay language patient facing materials supporting self-management, informed treatment decisions, and actionable aspects related to HR-QoL. 71 Following rigorous patient evaluation, the team leveraged the internet and made materials freely available in 20 languages on the COST Action website. The COST Action BM1105 model of patient engagement respects patient knowledge and expertise and has been recognized as a ‘best practice’ model for rare disease research. 72 The COST Action website also provided key links for peer-to-peer support to build a CHH patient community. To seal gaps and cracks in care, a structured, transition clinic was developed and implemented to ensure that adolescents and young adults were not lost to follow-up as they moved from pediatric to adult-oriented care. 73 – 75 In ongoing partnership with patients, we co-created additional patient-facing educational materials to help patients understand their genetic test results and actionable steps they could take in managing their health. 76 With patient leader Mr. Neil Smith, we used a mixed-methods approach (i.e., quantitative and qualitative) to inform more person centered approaches to genetic testing 77 and have helped advance rare disease research methodology 78 , 79 and generated ‘best practices’ for co-creation. 80 Our ongoing collaboration has generated seven jointly authored publications and Mr. Smith has presented at an international meeting. 81 In-person and virtual patient meetings co-organized with “I am HH” have reached more than 500 patients across 20 states and 18 countries to date. Patients submit their questions online to structure quarterly virtual meetings that are responsive to patient priorities (i.e., treatment options, physical/mental health, and HR-Qol) while building community and fostering respect and trust. Patients were key stakeholders in co-designing the website ( www.myreproductivehealth.org ) as part of the P50 Massachusetts General Hospital – Harvard Center for Reproductive Medicine. The co-design process centered the patient perspective. Patients chose the site name, color scheme, images, co-created content, and help curate and contribute new content. Currently, collaborative work is underway to launch a natural history study as well as developing, implementing and evaluating psychosocial interventions supporting well-being and HR-QoL. This exemplar case shows how patient partnerships, community-based participatory methods, as well as co-creation/co-design have helped advance comprehensive, quality care for CHH internationally that is responsive to patient priorities. Exemplar 2 (RN): systemic sclerosis Systemic sclerosis (SSc) is a rare, multisystemic, autoimmune disorder of the connective tissues. Like many RDs, it is poorly understood yet has significant morbidity including multi-organ damage/failure resulting in increased mortality and significantly impaired HR-QoL. 82 Incidence of SSc is between 3.7–23 per million with prevalence estimated to be 50–300 cases per million. Unlike other autoimmune diseases, no drug treatments exist for the many different organ manifestations. As such, many non-pharmacologic treatments are often employed and multidisciplinary approaches to care are scant. 82 Individuals with SSc have numerous unmet health and information needs, are challenged to find expert care, and often struggle to navigate and coordinate care across multiple specialties. Not surprisingly, individuals with SSc have diminished HR-QoL. A Swiss nurse, Agnes Kocher has led the drive to develop a new model of chronic care for SSc bringing together diverse and complementary perspectives to inform this novel approach to SSc care “MANagement Of Systemic Sclerosis (MANOSS). 83 She drew on her lengthy clinical expertise working with SSc patients, leveraged community engagement, and employed a rigorous mixed-methods approach to inform the new model of care. Kocher and colleagues identified current practice patterns and technology readiness that informed a novel digitally enhanced (e-health) adaptation of the Chronic Care Model. 84 The team found that patients preferred the ease of the internet for learning about SSc - yet they expressed a need and desire for support in finding reliable sources and evaluating online health information. The initial study identified a key target for a nurse-led interventions providing guidance and support in finding and evaluating information in parallel with educational interventions to enhance patient e-health literacy skills. 85 Subsequently, Kocher and colleagues translated and validated a disease-specific patient-reported outcome measure, the Systemic Sclerosis Quality of Life Questionnaire. 86 This linguistically and culturally adapted instrument enables nurses to identify specific areas of concern and tailor SSc interventions accordingly. Further work assessed chronic care needs and quality of life among patients with SSc. 87 Findings indicated that patients with SSc reported significant gaps in follow-up and care coordination. Importantly, better care coordination was associated with better HR-QoL. Patients with SSc desired more care coordination, better access to specialists, and improved support for self-management. Identifying priority areas that mattered most to patients with SSc informed development of tailored interventions including specific interventions addressing skin/mucosa problems 88 and gastrointestinal symptoms. 89 Recognizing the significant contributions to advancing person-centered approaches to SSc care, the European Alliance of Associations for Rheumatology (EULAR) invited Kocher to help create international recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis. 90 This body of work highlights a number of important ways that nursing has improved high quality, comprehensive care for SSc. First, nursing helped patients develop e-health literacy to find and appraise SSc information online. Second, nursing plays a crucial role in coordinating SSc care across multiple specialists and ensuring follow-up/continuity of care to support improved HR-QoL. Tailored therapeutic education on SSc disease management strategies, treatment options, and coping strategies support patient activation and empowerment. In addition, nurses can help patients manage complex SSc symptoms while self-management support helps patients build self-care confidence. Last, the nurse-led needs assessment using validated measures provided deep insights into unmet health and information needs of patients and the impact on HR-QoL. By partnering with patients and other stakeholders, the nurse-led needs assessment informed a novel e-health adapted Chronic Care Model (MANOSS) for comprehensive, quality SSc care that is responsive to patient priorities. Discussion Rare diseases are complex and while individually infrequent, the cumulative impact of the roughly 7,000 RDs have enormous implications for public health and healthcare systems. Delays in diagnosis (diagnostic odyssey), difficulty finding expert care, inadequate care coordination across multiple specialists, geographic barriers, financial burden, lack of treatments, as well as stigma and isolation all pose significant obstacles to health and well-being in patients and families affected by RDs. These challenges and inequities place RDs in the realm of health disparities. Further, RD health disparities can be compounded by social determinants of health that magnify physical, psychosocial, and financial challenges. Despite the significant barriers, a number of promising developments have helped improve care of RDs. A key development in relation to delays in diagnosis have come from advances in genetic testing, including NGS and bioinformatic pipelines that have helped shorten the diagnostic odyssey for many RD patients 91 – yet access inequities exist. 21 The relatively recent emergence of AI/ML hold promise for accelerating diagnosis of RDs. 23 For example, it is unreasonable to expect healthcare providers to be able to recognize the roughly 7,000 RDs, yet it is plausible that AI/ML could comb electronic health record data to identify symptom patterns that point to a RD diagnosis thereby shortening the diagnostic odyssey. Patients are typically challenged to find knowledgeable providers in their particular RD. Newly launched education programs for providers on RDs, such as Medics 4 Rare Diseases ( Box 2 ) are an important means for closing this gap. 92 Moreover, when patients/families are able to find expert care they are frequently challenged to navigate care across multiple providers/specialists. The E.U. has enacted a number of initiatives to address these gaping needs including the Cross Border Healthcare Directive that enables individuals to access specialized centers within Europe and European Reference Networks for RD care. 93 Such RD centers of excellence typically include multidisciplinary, interprofessional teams that can provide a centralized location to address care needs thus alleviating some navigation barriers. By definition, RDs are geographically dispersed posing challenges for access to care and contributing to financial burden (i.e., travel). Increasingly widespread internet access has been tremendously important for RD communities. 94 Individuals and families affected by RDs are internet “power users” who learn about their condition online and connect with patient communities for crucial peer-to-peer support. 95 Internet connectivity also enables digital communication and virtual consultations that help patients overcome geographic distance and costly travel. 96 This is critical for RDs as multidisciplinary teams with expertise in a particular condition are typically located at academic medical centers that are often at a significant distance form where RD patients live, work, play, and worship. For healthcare systems, the magnitude costs associated with RDs is significant 97 as frequent hospitalization (and readmission) are common for RD that are typically medically complex. 98 The financial ramifications of RDs also include costly treatments - if they are available at all. Policy initiatives such as the U.S. Orphan Drug Act have been enacted to promote drug development in the form of tax credits and 7-years of market exclusivity – yet there is concern that pharmaceutical companies may be taking advantage of the Orphan drug status. 99 As such, the economic impact of RDs have major public policy implications that are often hotly debated. 100 The psychosocial burden of RDs affect patients and families on a daily basis. Organizations such the NORD, Canadian Organization for Rare Disorders (CORD), EURORDIS, Orphanet, and the Genetic Alliance ( Box 2 ) have helped proliferate the number of patient organizations. Such organizations play key roles in providing psychosocial support, advocacy, and are drivers of creating patient registries and launching natural history studies. Patient registries are crucial for accelerating clinical trial readiness for testing investigational drugs/devices and bringing new treatments to market. 101 Similarly, natural history studies provide insights into poorly understood RDs and can identify both unmet needs and possible targets for improving treatment/care. 102 As shown in the exemplar cases, understanding the lived experiences of patients with RDs can help improve the care of RDs. 103 Importantly, patient organizations enable peer-to-peer support, crowdsourcing solutions, and advocacy/lobbying for policy change. There are several critical future directions for advancing the care of RDs. 2 There is a need to grow and expand patient organizations and foster collaboration with stakeholders including healthcare providers, researchers, drug developers, and governments. Workforce development is needed to develop expertise in specific (groups of) RDs. Transdisciplinary and interprofessional approaches are needed to implement novel, integrated care models, accelerate diagnosis, and propel RD research. Global data sharing, harmonized definitions (i.e., accurate and comprehensive coding International Classification of Diseases [ICD-10]), and enhanced international collaboration are needed to elucidate RDs and speed development of much needed treatments. Finally, more resources and funding (i.e., government, industry and philanthropy) are needed to address the significant public health need of RDs. Summary Rare genetic disorders pose significant challenges for patients, families, healthcare providers, and health systems. As the most numerous and trusted of trained healthcare professionals 26 27 , nursing is well suited to help meet the needs of patients/families affected by genetic RDs. As highlighted in exemplar cases, nurse-led interventions, community engagement, and research have helped improve comprehensive care for RDs. Such work aims to empower patients, improve health and psychosocial well-being and bridge disparities. While the RD community faces significant challenges, nursing has an integral role in interprofessional approaches to deliver comprehensive, quality care for RDs. Key Points. Rare diseases are individually infrequent yet the cumulative public health impact of the ~7,000 rare diseases is large. Rare diseases are predominantly genetic in etiology and are often overlooked and neglected – sometimes called “orphan” diseases. Patients and families affected by rare diseases face numerous challenges and inequities that place them in the realm of health disparities. Culturally empowered, person-centered approaches are needed to optimize health and wellness in people living with rare diseases. Nurses play a key role in patient advocacy and providing comprehensive, holistic care for rare diseases. Synopsis. Rare diseases are predominantly genetic in etiology and characterized by low frequency and high medical complexity. While individually infrequent, the cumulative public health impact of ~7,000 rare diseases is significant and patients and families experience significant psychosocial burden. Health disparities stem from delays in diagnosis (diagnostic odyssey), difficulty accessing care, and lack of effective treatments. This review provides an overview of rare genetic diseases and highlights exemplar cases demonstrating nursing’s role in advancing comprehensive, person-centered care for rare genetic diseases. Resources and recommendations are provided for nurses to enhance quality care for individuals and families living with rare diseases. Clinics Care Points. Nurses can provide crucial psychological and emotional support for patients and families affected by rare genetic diseases. Nurses can help shorten the diagnostic odyssey by advocating for genetic testing and providing and decisional support. Nurses can be integral in care coordination and assisting patient and families in navigating multiple specialists and a complex healthcare ecosystem. Nurse-led therapeutic education can help patients/families develop self-management skills and empower individuals thereby promoting independence and wellness. Disclosures The authors have no relevant disclosures or perceived conflicts of interest. Dr. Dwyer serves on Massachusetts Rare Disease Advisory Council (Boston MA) and receives support from the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development (1P50HD104224-01) and the Josiah Macy Jr. Foundation. Views expressed in this article do not necessarily reflect those of the Massachusetts Rare Disease Advisory Council. Dr. Somanadhan serves as the Co-Lead of the All-Ireland Rare Diseases Interdisciplinary Research Network (RAiN), the Co-Principal Investigator and co-lead of the Rare Disease Research Catalyst Consortium (RDCat) funded by the Health Research Board Ireland, and a co-applicant of Horizon Europe’s rare disease consortium, ERDERA—EUROPEAN RARE DISEASES RESEARCH ALLIANCE. Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Contributor Information Andrew A. Dwyer, Associate Professor, William F. 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